Methods of treating HIV with categravir and rilpivirine in pediatric patients

Abstract

The present disclosure provides methods of treating HIV infection in a human pediatric patient by administering a combination of categravir, or a pharmaceutically acceptable salt thereof, and rilpivirine, or a pharmaceutically acceptable salt thereof.

Description

Technical Field

[0001] The present disclosure relates to methods of treating HIV infection in human pediatric patients by administering a combination of cabotegravir, or a pharmaceutically acceptable salt thereof, and rilpivirine, or a pharmaceutically acceptable salt thereof. Background Art

[0002] Decades of advances in antiretroviral therapy (ART) have led to simplified treatment regimens for people infected with the human immunodeficiency virus (HIV-1). Viral suppression in adults is often achieved through strict adherence to a once-daily, single-tablet ART regimen. However, viral suppression rates in children are low compared with those in adults. The lack of pediatric formulations and potent regimens for children has led to difficulties with adherence and low suppression rates. The ART safety profile has gradually improved, allowing for the inclusion of well-tolerated drugs with few side effects in treatment regimens. Despite advances in ART in older populations, fewer simplified HIV-1 regimens are available for younger children. The same barriers that have led to suboptimal pediatric ART adherence have also delayed pediatric clinical trials of drugs approved in adults, compounding the barriers faced by children infected with HIV-1.

[0003] In addition, normal childhood weight gain requires phased changes in weight-based dosing of ART, making it difficult to produce a single fixed-dose combination formulation containing multiple antiretroviral drugs whose doses can be adjusted as the child grows. In addition, young children have difficulty swallowing tablets, requiring the development of specific drug formulations (ie, liquid, dispersible tablets) for this relatively small patient population, further delaying the availability of new drugs.

[0004] CAB and Rilpivirine (RPV) are the first long-acting (LA) injectable ARTs approved for the treatment of HIV-1. CAB is a potent integrase strand transfer inhibitor (INSTI) with properties that allow for formulation and delivery as a LA parenteral product. RPV (also formulated as a LA product) is a diarylpyrimidine derivative and a potent non-nucleoside reverse transcriptase inhibitor (NNRTI). The combination of CAB LA plus RPV LA has an acceptable safety profile and is well tolerated and effective as a dual injectable ART in virally suppressed HIV-1 infected adults and adolescents (12 years of age and older). CABENUVA is a two-drug combination of cartegravir and rilpivirine that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection in adults and adolescents aged 12 years and older who weigh at least 35 kg and are virologically suppressed (HIV-1 RNA <50 copies / mL) on a stable antiretroviral regimen, have no history of treatment failure, and have no known or suspected resistance to cartegravir or rilpivirine. The recommended dosing of CABENUVA is once a month or once every two months. Summary of the invention

[0005] In one aspect, the present disclosure provides a method of treating HIV infection, comprising: administering to a human in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; and thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; wherein the human is 2 years old to less than 12 years old.

[0006] In one aspect, the present disclosure provides a method for treating HIV infection, the method comprising: administering to a human in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; and thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; wherein the age of the human is from 2 years to less than 12 years; and wherein: (a) the weight of the human is from 35 kg to less than 40 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 900 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 400 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 600 mg intramuscular injection; (b) the human has a body weight of 25 kg to 34.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection; (c) the human has a body weight of 20 kg to 24.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection. mg intramuscular injection; (d) the human weighs 14 kg to 19.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection; or (e) the human weighs 10 kg to 13.9 kg; a loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection. .

[0007] In one aspect, the present disclosure provides the use of (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating HIV infection in a human, wherein the human is aged from 2 years to less than 12 years, and the medicament is formulated for regular intramuscular injection.

[0008] In one aspect, the present disclosure provides cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for use in treating HIV infection in a human, wherein the human is between 2 years old and less than 12 years old, and cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for regular intramuscular injection.

[0009] In one aspect, the present disclosure provides cartegravir or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with rilpivirine or a pharmaceutically acceptable salt thereof for treating HIV infection in a human, wherein the human is 2 years old to less than 12 years old, and cartegravir or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is formulated for intramuscular injection.

[0010] In one aspect, the present disclosure provides rilpivirine or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with cartegravir or a pharmaceutically acceptable salt thereof for treating HIV infection in a human, wherein the human is 2 years old to less than 12 years old, and rilpivirine or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection. In one embodiment, cartegravir or a pharmaceutically acceptable salt thereof is formulated for intramuscular injection.

[0011] The disclosed methods, including use of LA injectable ART, advantageously improve treatment adherence compared to existing therapies, thereby enabling sustained viral suppression in children infected with HIV-1. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present disclosure provides a method for treating HIV infection in human pediatric patients by administering a combination of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof. The method comprises regularly administering an intramuscular injection of (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof to a human pediatric patient in need thereof. The age of the human pediatric patient is 2 years old to less than 12 years old.

[0014] In some embodiments, the human is virally suppressed, i.e., exhibits a viral load of less than or equal to (particularly less than) 50 copies of HIV-1 RNA per mL of plasma before starting treatment. In some embodiments, after at least 72 weeks of treatment with cartegravir and rilpivirine (including optional oral introduction during treatment), the human exhibits a viral load of less than or equal to 50 copies of HIV-1 RNA per mL of plasma.

[0015] Intramuscular administration.

[0016] In one aspect, the present disclosure provides a method of treating HIV infection, comprising: administering to a human in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; and thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; wherein the human is 2 years old to less than 12 years old.

[0017] In some embodiments, the human body weight is 10 kg to less than 40 kg, preferably 10 kg to 34.9 kg. In some embodiments, the human body weight is 10 kg to 13.9 kg, 14 kg to 19.9 kg, 20 kg to 24.9 kg, 25 kg to 34.9 kg or 35 kg to less than 40 kg. In some embodiments, the dosage of patients in different weight intervals is different, and patients in the lighter weight interval receive a lower dosage of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof than patients in the heavier weight interval.

[0018] In some embodiments, the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof. In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof.

[0019] In some embodiments, cartegravir or its pharmaceutically acceptable salt is administered as 50 mg to 600 mg intramuscular injection, preferably 100 mg to 600 mg intramuscular injection, 150 mg to 600 mg intramuscular injection, 200 mg to 600 mg intramuscular injection, 300 mg to 600 mg intramuscular injection or 200 mg to 600 mg intramuscular injection. In one embodiment, cartegravir or its pharmaceutically acceptable salt is administered as 200 mg to 600 mg intramuscular injection. In one embodiment, cartegravir or its pharmaceutically acceptable salt is administered as 300 mg to 600 mg intramuscular injection. In one embodiment, cartegravir or its pharmaceutically acceptable salt is administered as 200 mg to 400 mg intramuscular injection. In some embodiments, cartegravir or its pharmaceutically acceptable salt is administered as 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg intramuscular injection.

[0020] In some embodiments, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 50 mg to 600 mg intramuscular injection, preferably 100 mg to 600 mg intramuscular injection, 150 mg to 600 mg intramuscular injection, 200 mg to 600 mg intramuscular injection or 300 mg to 600 mg intramuscular injection. In one embodiment, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 200 mg to 600 mg intramuscular injection. In one embodiment, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 300 mg to 600 mg intramuscular injection. In some embodiments, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg intramuscular injection.

[0021] In some embodiments, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 50 mg to 600 mg intramuscular injections, preferably 100 mg to 600 mg intramuscular injections, 150 mg to 600 mg intramuscular injections, 200 mg to 600 mg intramuscular injections, or 200 mg to 400 mg intramuscular injections. In one embodiment, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 200 mg to 600 mg intramuscular injections. In one embodiment, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 200 mg to 400 mg intramuscular injections. In some embodiments, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg intramuscular injections.

[0022] In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg to 900 mg intramuscular injection, preferably as a 100 mg to 900 mg intramuscular injection, a 150 mg to 900 mg intramuscular injection, a 200 mg to 900 mg intramuscular injection, a 250 mg to 900 mg intramuscular injection, a 300 mg to 900 mg intramuscular injection, a 450 mg to 900 mg intramuscular injection, or a 300 mg to 600 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 900 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg to 900 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 600 mg intramuscular injection. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg intramuscular injection.

[0023] In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg to 900 mg intramuscular injection, preferably as a 100 mg to 900 mg intramuscular injection, a 150 mg to 900 mg intramuscular injection, a 200 mg to 900 mg intramuscular injection, a 250 mg to 900 mg intramuscular injection, a 450 mg to 900 mg intramuscular injection, or a 300 mg to 900 mg intramuscular injection. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 900 mg intramuscular injection. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg to 900 mg intramuscular injection. In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg intramuscular injection.

[0024] In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as 50 mg to 900 mg intramuscular injections, preferably 100 mg to 900 mg intramuscular injections, 150 mg to 900 mg intramuscular injections, 200 mg to 900 mg intramuscular injections, 250 mg to 900 mg intramuscular injections, 300 mg to 900 mg intramuscular injections, or 300 mg to 600 mg intramuscular injections. In one embodiment, a maintenance dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as 300 mg to 900 mg intramuscular injections. In one embodiment, a maintenance dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as 300 mg to 600 mg intramuscular injections. In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg intramuscular injection.

[0025] It should be understood that disclosure of the amount of rilpivirine or a pharmaceutically acceptable salt thereof in the form of an injection (eg, in mg) includes disclosure of the amount expressed in base equivalents.

[0026] In some embodiments, the interval between the administration of the loading dose of cartegravir or a pharmaceutically acceptable salt thereof and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is less than 1 hour, preferably less than 30 minutes, less than 20 minutes, less than 15 minutes, less than 10 minutes, or less than 5 minutes. In some embodiments, for each maintenance dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof, the interval between the administration of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is less than 1 hour, preferably less than 30 minutes, less than 20 minutes, less than 15 minutes, less than 10 minutes, or less than 5 minutes.

[0027] In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof is administered first, followed by rilpivirine or a pharmaceutically acceptable salt thereof. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is administered first, followed by cartegravir or a pharmaceutically acceptable salt thereof.

[0028] In some embodiments, the intramuscular injection is administered at a site selected from the gluteus medius or the lateral thigh.

[0029] In some embodiments, the intramuscular injection of cartegravir or its pharmaceutically acceptable salt is administered in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL. In some embodiments, the intramuscular injection of cartegravir or its pharmaceutically acceptable salt is 200 mg / mL and is administered in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL. In some embodiments, the intramuscular injection of rilpivirine or its pharmaceutically acceptable salt is administered in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL. In some embodiments, the intramuscular injection of rilpivirine or its pharmaceutically acceptable salt is 300 mg / mL and is administered in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL.

[0030] Intramuscular dosing interval.

[0031] In some embodiments, one or more maintenance doses are administered at fixed intervals. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently. In some embodiments, one or more maintenance doses are administered once every month ± 7 days or once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every month ± 7 days. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days. In some embodiments, one or more maintenance doses are administered once every 8 weeks ± 7 days.

[0032] In some embodiments, one or more maintenance doses are applied for a period of time at fixed intervals, then applied at different fixed intervals (e.g., longer fixed intervals). In some embodiments, one or more maintenance doses are applied once per month ± 7 days or once per 4 weeks ± 7 days, then once per two months ± 7 days or once per 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are applied once per month ± 7 days or once per 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 times (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 dosages), then once per two months ± 7 days or once per 8 weeks ± 7 days for maintenance dose. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by a maintenance dose administered once every two months ± 7 days or once every 8 weeks ± 7 days for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times.

[0033] Oral infusion dose.

[0034] In some embodiments, an oral lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is administered prior to the loading dose. Thus, in some embodiments, the method further comprises orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose.

[0035] In some embodiments, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more dispersible tablets. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more tablets dispersed in a liquid.

[0036] In some embodiments, the introductory doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered with food.

[0037] In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 5 mg to 30 mg daily dose of acid equivalents, preferably 10 mg to 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 10 mg to 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 5 mg, 10 mg, 15 mg, 20 mg, 25 mg or 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 10 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is administered in a tablet of 30 mg acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is administered in a tablet of 30 mg acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is administered in a dispersible tablet of 5 mg acid equivalents, one, two, three, four or five. In some embodiments, the introductory dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0038] In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 2.5 mg to 25 mg base equivalents per day, preferably 12.5 mg to 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 12.5 mg to 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg or 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 12.5 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 15 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as one 25 mg base equivalent tablet. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as one, two, three, four, five, six, seven or eight 2.5 mg tablets, preferably as tablets dispersed in a liquid. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as five 2.5 mg tablets, preferably as tablets dispersed in a liquid. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as six 2.5 mg tablets, preferably as tablets dispersed in a liquid.

[0039] In some embodiments, the cartegravir or a pharmaceutically acceptable salt thereof in the oral formulation is in the form of cartegravir sodium. In some embodiments, the rilpivirine or a pharmaceutically acceptable salt thereof in the oral formulation is in the form of a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0040] Oral bridging dose.

[0041] In some embodiments, an oral bridging dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is administered to a person in place of a scheduled intramuscular injection. Thus, in some embodiments, the method further comprises orally administering a bridging dose of cartegravir or a pharmaceutically acceptable salt thereof and / or rilpivirine or a pharmaceutically acceptable salt thereof, in particular a bridging dose once daily, in place of a scheduled intramuscular injection, in particular in a person who will miss or has missed a scheduled intramuscular injection. In one embodiment, the first oral bridging dose is administered on the day of the missed intramuscular injection or on the day of the missed intramuscular injection ±7 days. In one embodiment, the last oral bridging dose is administered on the day of resuming the intramuscular injection, in particular before the day of resuming the intramuscular injection.

[0042] preparation.

[0043] The injection of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is in the form of a long-acting preparation.

[0044] In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is a suspension formulation, in particular a prolonged-release suspension for injection or an extended-release suspension for injection. In some embodiments, the cartegravir or its pharmaceutically acceptable salt in the long-acting formulation is in the form of cartegravir free base. In some embodiments, the concentration of cartegravir or its pharmaceutically acceptable salt in the suspension is 200 mg / mL. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is present in a single-dose vial in an amount of 400 mg in a 2 mL volume. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is present in a single-dose vial in an amount of 600 mg in a 3 mL volume. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises cartegravir or its pharmaceutically acceptable salt, polysorbate and polyethylene glycol. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises cartegravir or its pharmaceutically acceptable salt, mannitol, polysorbate (e.g., polysorbate 20 or polysorbate 80), polyethylene glycol (PEG) (e.g., PEG 3350), and water for injection. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises 200 mg / mL cartegravir, 35 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG 3350, and water for injection. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises 200 mg / mL cartegravir, 45 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG3350, and water for injection.

[0045] In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is a suspension formulation, in particular an extended release suspension for injection or a sustained release suspension for injection. In some embodiments, the rilpivirine or a pharmaceutically acceptable salt thereof in the long-acting formulation is in the form of rilpivirine free base. In some embodiments, the concentration of rilpivirine or a pharmaceutically acceptable salt thereof in the suspension is 300 mg / mL, in particular 300 mg base equivalent / mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 600 mg base equivalent in a volume of 2 mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 900 mg base equivalent in a volume of 3 mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises rilpivirine or a pharmaceutically acceptable salt thereof and poloxamer. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises rilpivirine or a pharmaceutically acceptable salt thereof, citric acid and poloxamer. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises 300 mg / mL rilpivirine, 1 mg / mL citric acid monohydrate, 50 mg / mL poloxamer 338 and water for injection. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises 300 mg / mL rilpivirine, 1 mg / mL citric acid monohydrate, 50 mg / mL poloxamer 338, water for injection, glucose monohydrate, sodium dihydrogen phosphate monohydrate and sodium hydroxide for adjusting pH.

[0046] In some embodiments, the injection of cartegravir or its pharmaceutically acceptable salt is formulated as a suspension, and cartegravir or its pharmaceutically acceptable salt is in free form (i.e., non-salt form), and the injection of rilpivirine or its pharmaceutically acceptable salt is formulated as a suspension, and rilpivirine or its pharmaceutically acceptable salt is in free form (i.e., non-salt form). In some embodiments, the injection of cartegravir or its pharmaceutically acceptable salt is formulated as a suspension, and cartegravir or its pharmaceutically acceptable salt is in free acid / base form, and the injection of rilpivirine or its pharmaceutically acceptable salt is formulated as a suspension, and rilpivirine or its pharmaceutically acceptable salt is in free base form.

[0047] Used to treat HIV.

[0048] In one aspect, the present disclosure provides the use of (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating HIV infection in a human, wherein the age of the human is 2 years to less than 12 years, and the medicament is formulated for regular intramuscular injection. In one aspect, the present disclosure provides a loading dose comprising (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof; and one or more maintenance doses comprising (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating HIV infection in a human, wherein the age of the human is 2 years to less than 12 years, and the loading dose and one or more maintenance doses are formulated for intramuscular injection. In one aspect, the present disclosure provides cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for use in treating HIV infection in a human, wherein the human is between 2 years old and less than 12 years old, and cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for regular intramuscular injection.

[0049] In some embodiments, the human body weight is 10 kg to less than 40 kg, preferably 10 kg to 34.9 kg. In some embodiments, the human body weight is 10 kg to 13.9 kg, 14 kg to 19.9 kg, 20 kg to 24.9 kg, 25 kg to 34.9 kg or 35 kg to less than 40 kg. In some embodiments, the dosage used for patients in different weight intervals is different, and the dosage of cartegravir or its pharmaceutically acceptable salt and rilpivirine or its pharmaceutically acceptable salt used by patients in the lighter weight interval is lower than that of patients in the heavier weight interval.

[0050] In some embodiments, the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof. In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof.

[0051] In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 50 mg to 600 mg intramuscular injection, preferably a 100 mg to 600 mg intramuscular injection, a 150 mg to 600 mg intramuscular injection, a 200 mg to 600 mg intramuscular injection, a 300 mg to 600 mg intramuscular injection, or a 200 mg to 400 mg intramuscular injection. In one embodiment, cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg to 600 mg intramuscular injection. In one embodiment, cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg to 600 mg intramuscular injection. In one embodiment, cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg to 400 mg intramuscular injection. In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg intramuscular injection.

[0052] In some embodiments, the loading dose of cartegravir or its pharmaceutically acceptable salt is formulated as 50 mg to 600 mg intramuscular injection, preferably 100 mg to 600 mg intramuscular injection, 150 mg to 600 mg intramuscular injection, 200 mg to 600 mg intramuscular injection or 300 mg to 600 mg intramuscular injection. In one embodiment, the loading dose of cartegravir or its pharmaceutically acceptable salt is formulated as 200 mg to 600 mg intramuscular injection. In one embodiment, the loading dose of cartegravir or its pharmaceutically acceptable salt is formulated as 300 mg to 600 mg intramuscular injection. In some embodiments, the loading dose of cartegravir or its pharmaceutically acceptable salt is formulated as 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg intramuscular injection.

[0053] In some embodiments, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are formulated as 50 mg to 600 mg intramuscular injections, preferably 100 mg to 600 mg intramuscular injections, 150 mg to 600 mg intramuscular injections, 200 mg to 600 mg intramuscular injections or 200 mg to 400 mg intramuscular injections. In one embodiment, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are formulated as 200 mg to 600 mg intramuscular injections. In one embodiment, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered with 200 mg to 400 mg intramuscular injections. In some embodiments, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are formulated as 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg intramuscular injections.

[0054] In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 50 mg to 900 mg intramuscular injection, preferably a 100 mg to 900 mg intramuscular injection, a 150 mg to 900 mg intramuscular injection, a 200 mg to 900 mg intramuscular injection, a 250 mg to 900 mg intramuscular injection, a 300 mg to 900 mg intramuscular injection, a 450 mg to 900 mg intramuscular injection, or a 300 mg to 600 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 900 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg to 900 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 600 mg intramuscular injection. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg intramuscular injection.

[0055] In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 50 mg to 900 mg intramuscular injection, preferably a 100 mg to 900 mg intramuscular injection, a 150 mg to 900 mg intramuscular injection, a 200 mg to 900 mg intramuscular injection, a 250 mg to 900 mg intramuscular injection, a 450 mg to 900 mg intramuscular injection, or a 300 mg to 900 mg intramuscular injection. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 900 mg intramuscular injection. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg to 900 mg intramuscular injection. In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg intramuscular injection.

[0056] In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are formulated as 50 mg to 900 mg intramuscular injections, preferably 100 mg to 900 mg intramuscular injections, 150 mg to 900 mg intramuscular injections, 200 mg to 900 mg intramuscular injections, 250 mg to 900 mg intramuscular injections, 300 mg to 900 mg intramuscular injections, or 300 mg to 600 mg intramuscular injections. In one embodiment, a maintenance dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 900 mg intramuscular injection. In one embodiment, a maintenance dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 600 mg intramuscular injection. In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg intramuscular injection.

[0057] It should be understood that disclosure of the amount of rilpivirine or a pharmaceutically acceptable salt thereof in the form of an injection (eg, in mg) includes disclosure of the amount expressed in base equivalents.

[0058] In some embodiments, one or more maintenance doses are formulated for administration at fixed intervals. In some embodiments, one or more maintenance doses are formulated for administration once every 4 weeks ± 7 days or with lower frequency. In some embodiments, one or more maintenance doses are formulated for administration once every month ± 7 days or once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once every month ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once every 8 weeks ± 7 days.

[0059] In some embodiments, one or more maintenance doses are formulated for administration at fixed intervals over a period of time, followed by administration at different fixed intervals, e.g., longer fixed intervals. In some embodiments, one or more maintenance doses are formulated for administration once per month ± 7 days or once per 4 weeks ± 7 days, followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 doses are administered) followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times.

[0060] In some embodiments, the medicament further comprises an oral introduction dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for administration prior to the loading dose. Therefore, in some embodiments, the use further comprises preparing an introduction dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for oral administration prior to the loading dose.

[0061] In some embodiments, the introductory dose of cartegravir or a pharmaceutically acceptable salt thereof is formulated for administration in the form of one or more tablets or one or more dispersible tablets. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration in the form of one or more tablets or one or more tablets dispersed in a liquid.

[0062] In some embodiments, the introductory doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for administration with food.

[0063] In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 5 mg to 30 mg daily dose of acid equivalents, preferably 10 mg to 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 10 mg to 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 5 mg, 10 mg, 15 mg, 20 mg, 25 mg or 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 10 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is formulated for administration with a tablet of 30 mg acid equivalents. In some embodiments, the introductory dose of cartegravir or a pharmaceutically acceptable salt thereof is formulated for administration as one, two, three, four, or five 5 mg acid equivalent dispersible tablets. In some embodiments, the introductory dose of cartegravir or a pharmaceutically acceptable salt thereof is formulated for administration as two 5 mg acid equivalent dispersible tablets.

[0064] In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 2.5 mg to 25 mg base equivalents per day, preferably 12.5 mg to 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 12.5 mg to 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg or 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 12.5 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 15 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration in one 25 mg base equivalent tablet. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration in one, two, three, four, five, six, seven or eight 2.5 mg tablets, preferably in tablets dispersed in a liquid. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration in five 2.5 mg tablets, preferably in tablets dispersed in a liquid. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration in six 2.5 mg tablets, preferably in tablets dispersed in a liquid.

[0065] In some embodiments, the cartegravir or a pharmaceutically acceptable salt thereof in the oral formulation is in the form of cartegravir sodium. In some embodiments, the rilpivirine or a pharmaceutically acceptable salt thereof in the oral formulation is in the form of a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0066] In some embodiments, the medicament comprises an oral bridging dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for administration to a human being in place of a scheduled intramuscular injection. Thus, in some embodiments, the use further comprises an oral bridging dose, in particular a daily oral bridging dose of cartegravir or a pharmaceutically acceptable salt thereof and / or rilpivirine or a pharmaceutically acceptable salt thereof, for administration to a human being in place of a scheduled intramuscular injection, in particular for a human being who will miss or has missed a scheduled intramuscular injection. In one embodiment, the first oral bridging dose is provided on the day of the missed intramuscular injection or on the day of the missed intramuscular injection ±7 days. In one embodiment, the last oral bridging dose is provided on the day of the resumption of the intramuscular injection, in particular before the day of the resumption of the intramuscular injection.

[0067] In some embodiments, the medicament is suitable for administration to a human exhibiting a viral load of less than or equal to 50 copies of HIV-1 RNA per mL of plasma. In some embodiments, the use of the medicament in a human achieves a viral load of less than or equal to 50 copies of HIV-1 RNA per mL of plasma after at least 72 weeks.

[0068] In some embodiments, the loading dose of cartegravir or a pharmaceutically acceptable salt thereof and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof are formulated for administration less than 1 hour apart, preferably less than 30 minutes apart, less than 20 minutes apart, less than 15 minutes apart, less than 10 minutes apart, or less than 5 minutes apart. In some embodiments, for each maintenance dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof, cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for administration less than 1 hour apart, preferably less than 30 minutes apart, less than 20 minutes apart, less than 15 minutes apart, less than 10 minutes apart, or less than 5 minutes apart.

[0069] In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof is formulated for a first administration and rilpivirine or a pharmaceutically acceptable salt thereof is formulated for a second administration. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is formulated for a first administration and cartegravir or a pharmaceutically acceptable salt thereof is formulated for a second administration.

[0070] In some embodiments, the intramuscular injection is formulated for administration at a site selected from the gluteus medius or the lateral thigh.

[0071] In some embodiments, the intramuscular injection of cartegravir or its pharmaceutically acceptable salt is formulated in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL. In some embodiments, the intramuscular injection of cartegravir or its pharmaceutically acceptable salt is formulated in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL at a concentration of 200 mg / mL. In some embodiments, the intramuscular injection of rilpivirine or its pharmaceutically acceptable salt is formulated in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL. In some embodiments, the intramuscular injection of rilpivirine or its pharmaceutically acceptable salt is formulated in a volume of 0.5 mL, 1 mL, 1.5 mL, 2 mL, 2.5 mL, or 3 mL at a concentration of 300 mg / mL.

[0072] The injection of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is in the form of a long-acting preparation.

[0073] In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is a suspension formulation, in particular an extended release suspension for injection or a sustained release suspension for injection. In some embodiments, the concentration of cartegravir or its pharmaceutically acceptable salt in the suspension is 200 mg / mL. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is present in a single-dose vial in an amount of 400 mg in a 2 mL volume. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is present in a single-dose vial in an amount of 600 mg in a 3 mL volume. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises cartegravir or its pharmaceutically acceptable salt, polysorbate and polyethylene glycol. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises cartegravir or its pharmaceutically acceptable salt, mannitol, polysorbate (e.g., polysorbate 20 or polysorbate 80), polyethylene glycol (PEG) (e.g., PEG 3350), and water for injection. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises 200 mg / mL cartegravir, 35 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG 3350, and water for injection. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises 200 mg / mL cartegravir, 45 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG 3350, and water for injection. In some embodiments, the cartegravir or its pharmaceutically acceptable salt in the long-acting formulation is in the form of cartegravir free base.

[0074] In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is a suspension formulation, in particular an extended release suspension for injection or a sustained release suspension for injection. In some embodiments, the concentration of rilpivirine or a pharmaceutically acceptable salt thereof in the suspension is 300 mg / mL, in particular 300 mg base equivalent / mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 600 mg base equivalent in a volume of 2 mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 900 mg base equivalent in a volume of 3 mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises rilpivirine or a pharmaceutically acceptable salt thereof and poloxamer. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises rilpivirine or a pharmaceutically acceptable salt thereof, citric acid and poloxamer. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises 300 mg / mL rilpivirine, 1 mg / mL citric acid monohydrate, 50 mg / mL poloxamer 338, and water for injection. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises 300 mg / mL rilpivirine, 1 mg / mL citric acid monohydrate, 50 mg / mL poloxamer 338, water for injection, glucose monohydrate, sodium dihydrogen phosphate monohydrate, and sodium hydroxide for adjusting pH. In some embodiments, the rilpivirine or a pharmaceutically acceptable salt thereof in the long-acting formulation is in the form of rilpivirine free base.

[0075] In some embodiments, the injection of cartegravir or its pharmaceutically acceptable salt is formulated as a suspension, and cartegravir or its pharmaceutically acceptable salt is in free form (i.e., non-salt form), and the injection of rilpivirine or its pharmaceutically acceptable salt is formulated as a suspension, and rilpivirine or its pharmaceutically acceptable salt is in free form (i.e., non-salt form). In some embodiments, the injection of cartegravir or its pharmaceutically acceptable salt is formulated as a suspension, and cartegravir or its pharmaceutically acceptable salt is in free acid / base form, and the injection of rilpivirine or its pharmaceutically acceptable salt is formulated as a suspension, and rilpivirine or its pharmaceutically acceptable salt is in free base form.

[0076] Combination of cartegravir and rilpivirine.

[0077] In one aspect, the present disclosure provides cartegravir or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with rilpivirine or a pharmaceutically acceptable salt thereof for treating HIV infection in a human, wherein the age of the human is 2 years to less than 12 years, and cartegravir or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection. In one aspect, the present disclosure provides cartegravir or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with rilpivirine or a pharmaceutically acceptable salt thereof for treating HIV infection in a human, wherein the age of the human is 2 years to less than 12 years, and rilpivirine or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection. In one embodiment, cartegravir or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection.

[0078] In some embodiments, the human body weight is 10 kg to less than 40 kg, preferably 10 kg to 34.9 kg. In some embodiments, the human body weight is 10 kg to 13.9 kg, 14 kg to 19.9 kg, 20 kg to 24.9 kg, 25 kg to 34.9 kg or 35 kg to less than 40 kg. In some embodiments, the dosage for patients in different weight intervals is different, and a lower dosage of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is suitable for patients in a lighter weight interval compared to patients in a heavier weight interval.

[0079] In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof is provided in a loading dose and one or more maintenance doses, and the loading dose is greater than the one or more maintenance doses. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is provided in a loading dose and one or more maintenance doses, and the loading dose is greater than the one or more maintenance doses.

[0080] In some embodiments, cartegravir or its pharmaceutically acceptable salt is provided in a dose of 50 mg to 600 mg suitable for intramuscular injection, preferably 100 mg to 600 mg, 150 mg to 600 mg, 200 mg to 600 mg, 300 mg to 600 mg or 200 mg to 40 mg. In one embodiment, cartegravir or its pharmaceutically acceptable salt is provided in a dose of 200 mg to 600 mg suitable for intramuscular injection. In one embodiment, cartegravir or its pharmaceutically acceptable salt is provided in a dose of 300 mg to 600 mg suitable for intramuscular injection. In one embodiment, cartegravir or its pharmaceutically acceptable salt is provided in a dose of 200 mg to 400 mg suitable for intramuscular injection. In some embodiments, cartegravir or its pharmaceutically acceptable salt is provided in a dose of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg suitable for intramuscular injection.

[0081] In some embodiments, the loading dose of cartegravir or its pharmaceutically acceptable salt is provided in a dose of 50 mg to 600 mg suitable for intramuscular injection, preferably in a dose of 100 mg to 600 mg suitable for intramuscular injection, a dose of 150 mg to 600 mg suitable for intramuscular injection, a dose of 200 mg to 600 mg suitable for intramuscular injection, or a dose of 300 mg to 600 mg suitable for intramuscular injection. In one embodiment, the loading dose of cartegravir or its pharmaceutically acceptable salt is provided in a dose of 200 mg to 600 mg suitable for intramuscular injection. In one embodiment, the loading dose of cartegravir or its pharmaceutically acceptable salt is provided in a dose of 300 mg to 600 mg suitable for intramuscular injection. In some embodiments, the loading dose of cartegravir or its pharmaceutically acceptable salt is provided in a dose of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg suitable for intramuscular injection.

[0082] In some embodiments, one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are provided in a dose of 50 mg to 600 mg suitable for intramuscular injection, preferably in a dose of 100 mg to 600 mg suitable for intramuscular injection, a dose of 150 mg to 600 mg suitable for intramuscular injection, a dose of 200 mg to 600 mg suitable for intramuscular injection, or a dose of 200 mg to 400 mg suitable for intramuscular injection. In one embodiment, one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are provided in a dose of 200 mg to 600 mg suitable for intramuscular injection. In one embodiment, one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are provided in a dose of 200 mg to 400 mg suitable for intramuscular injection. In some embodiments, one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are provided in a dose of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg or 600 mg suitable for intramuscular injection.

[0083] In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is provided in a dose of 50 mg to 900 mg suitable for intramuscular injection, preferably in a dose of 100 mg to 900 mg suitable for intramuscular injection, a dose of 150 mg to 900 mg suitable for intramuscular injection, a dose of 200 mg to 900 mg suitable for intramuscular injection, a dose of 250 mg to 900 mg suitable for intramuscular injection, a dose of 300 mg to 900 mg suitable for intramuscular injection, a dose of 450 mg to 900 mg suitable for intramuscular injection, or a dose of 300 mg to 600 mg suitable for intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered in a dose of 300 mg to 900 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered in a dose of 450 mg to 900 mg intramuscular injection. In one embodiment, rilpivirine or a pharmaceutically acceptable salt thereof is administered in a dose of 300 mg to 600 mg intramuscular injection. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is provided in a dosage of 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg suitable for intramuscular injection.

[0084] In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided in a dose of 50 mg to 900 mg suitable for intramuscular injection, preferably in a dose of 100 mg to 900 mg suitable for intramuscular injection, a dose of 150 mg to 900 mg suitable for intramuscular injection, a dose of 200 mg to 900 mg suitable for intramuscular injection, a dose of 250 mg to 900 mg suitable for intramuscular injection, a dose of 300 mg to 900 mg suitable for intramuscular injection, or a dose of 450 mg to 900 mg suitable for intramuscular injection. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered in a 300 mg to 900 mg intramuscular injection. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered in a 450 mg to 900 mg intramuscular injection. In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided in a dose of 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg suitable for intramuscular injection.

[0085] In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are provided in a dose of 50 mg to 900 mg suitable for intramuscular injection, preferably in a dose of 100 mg to 900 mg suitable for intramuscular injection, a dose of 150 mg to 900 mg suitable for intramuscular injection, a dose of 200 mg to 900 mg suitable for intramuscular injection, a dose of 250 mg to 900 mg suitable for intramuscular injection, a dose of 300 mg to 900 mg suitable for intramuscular injection, or a dose of 300 mg to 600 mg suitable for intramuscular injection. In one embodiment, the maintenance dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 900 mg intramuscular injection. In one embodiment, the maintenance dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 600 mg intramuscular injection. In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is provided in a dose of 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg suitable for intramuscular injection.

[0086] It should be understood that disclosure of the amount of rilpivirine or a pharmaceutically acceptable salt thereof in the form of an injection (eg, in mg) includes disclosure of the amount expressed in base equivalents.

[0087] In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof further comprises an oral lead-in dose suitable for administration prior to a loading dose. Thus, in some embodiments, the formulated cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof further comprises an lead-in dose suitable for oral administration prior to a loading dose.

[0088] In some embodiments, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is provided for administration in the form of one or more tablets or one or more dispersible tablets. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided for administration in the form of one or more tablets or one or more tablets dispersed in a liquid.

[0089] In some embodiments, the incorporation doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are suitable for administration with food.

[0090] In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 5 mg to 30 mg daily dose of acid equivalents, preferably 10 mg to 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 10 mg to 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 5 mg, 10 mg, 15 mg, 20 mg, 25 mg or 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 10 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is 30 mg daily dose of acid equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is provided for administration in a tablet of 30 mg acid equivalents. In some embodiments, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is provided for administration as one, two, three, four or five 5 mg acid equivalent dispersible tablets. In some embodiments, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is provided for administration as two 5 mg acid equivalent dispersible tablets.

[0091] In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 2.5 mg to 25 mg base equivalents per day, preferably 12.5 mg to 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 12.5 mg to 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg or 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 12.5 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 15 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is 25 mg base equivalents per day. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided for administration in one 25 mg base equivalent tablet. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided for administration in one, two, three, four, five, six, seven or eight 2.5 mg tablets, preferably in a tablet dispersed in a liquid, for administration. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration in five 2.5 mg tablets, preferably in a tablet dispersed in a liquid. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration in six 2.5 mg tablets, preferably in a tablet dispersed in a liquid.

[0092] In some embodiments, the cartegravir or a pharmaceutically acceptable salt thereof in the oral formulation is in the form of cartegravir sodium. In some embodiments, the rilpivirine or a pharmaceutically acceptable salt thereof in the oral formulation is in the form of a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0093] In some embodiments, an oral bridging dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is provided to a person in place of a scheduled intramuscular injection. Thus, in some embodiments, the use further comprises providing an oral bridging dose of cartegravir or a pharmaceutically acceptable salt thereof and / or rilpivirine or a pharmaceutically acceptable salt thereof (particularly a once-daily bridging dose) in place of a scheduled intramuscular injection, particularly for a person who will miss or has missed a scheduled intramuscular injection. In one embodiment, the first oral bridging dose is provided on the day of the missed intramuscular injection or on ±7 days of the missed intramuscular injection. In one embodiment, the last oral bridging dose is provided on the day of resuming the intramuscular injection, particularly before the day of resuming the intramuscular injection.

[0094] In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are suitable for administration to a human exhibiting a viral load of less than or equal to 50 copies of HIV-1 RNA per mL of plasma. In some embodiments, cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof achieve a viral load of less than or equal to 50 copies of HIV-1 RNA per mL of plasma in a human after at least 72 weeks.

[0095] The injection of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is in the form of a long-acting preparation.

[0096] In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is a suspension formulation, in particular an extended release suspension for injection or a sustained release suspension for injection. In some embodiments, the concentration of cartegravir or its pharmaceutically acceptable salt in the suspension is 200 mg / mL. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is present in a single-dose vial in an amount of 400 mg in a 2 mL volume. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt is present in a single-dose vial in an amount of 600 mg in a 3 mL volume. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises cartegravir or its pharmaceutically acceptable salt, polysorbate and polyethylene glycol. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises cartegravir or its pharmaceutically acceptable salt, mannitol, polysorbate (e.g., polysorbate 20 or polysorbate 80), polyethylene glycol (PEG) (e.g., PEG 3350), and water for injection. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises 200 mg / mL cartegravir, 35 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG 3350, and water for injection. In some embodiments, the long-acting formulation of cartegravir or its pharmaceutically acceptable salt comprises 200 mg / mL cartegravir, 45 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG 3350, and water for injection. In some embodiments, the cartegravir or its pharmaceutically acceptable salt in the long-acting formulation is in the form of cartegravir free base.

[0097] In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is a suspension formulation, in particular an extended release suspension for injection or a sustained release suspension for injection. In some embodiments, the concentration of rilpivirine or a pharmaceutically acceptable salt thereof in the suspension is 300 mg / mL, in particular 300 mg base equivalent / mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 600 mg base equivalent in a volume of 2 mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 900 mg base equivalent in a volume of 3 mL. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises rilpivirine or a pharmaceutically acceptable salt thereof and poloxamer. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises rilpivirine or a pharmaceutically acceptable salt thereof, citric acid and poloxamer. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises 300 mg / mL rilpivirine, 1 mg / mL citric acid monohydrate, 50 mg / mL poloxamer 338, and water for injection. In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises 300 mg / mL rilpivirine, 1 mg / mL citric acid monohydrate, 50 mg / mL poloxamer 338, water for injection, glucose monohydrate, sodium dihydrogen phosphate monohydrate, and sodium hydroxide for adjusting pH. In some embodiments, the rilpivirine or a pharmaceutically acceptable salt thereof in the long-acting formulation is in the form of rilpivirine free base.

[0098] In some embodiments, the injection of cartegravir or its pharmaceutically acceptable salt is formulated as a suspension, and cartegravir or its pharmaceutically acceptable salt is in free form (i.e., non-salt form), and the injection of rilpivirine or its pharmaceutically acceptable salt is formulated as a suspension, and rilpivirine or its pharmaceutically acceptable salt is in free form (i.e., non-salt form). In some embodiments, the injection of cartegravir or its pharmaceutically acceptable salt is formulated as a suspension, and cartegravir or its pharmaceutically acceptable salt is in free acid / base form, and the injection of rilpivirine or its pharmaceutically acceptable salt is formulated as a suspension, and rilpivirine or its pharmaceutically acceptable salt is in free base form.

[0099] Exemplary Dosing Regimens.

[0100] In some embodiments, the human body weight interval is 35 kg to less than 40 kg, and cartegravir or its pharmaceutically acceptable salt is administered as 400 mg to 600 mg intramuscular injection, and rilpivirine or its pharmaceutically acceptable salt is administered as 600 mg to 900 mg intramuscular injection. In some embodiments, the human body weight is 35 kg to less than 40 kg, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 600 mg intramuscular injection, and the loading dose of rilpivirine or its pharmaceutically acceptable salt is administered as 900 mg intramuscular injection. In some embodiments, the human body weight is 35 kg to less than 40 kg, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 400 mg intramuscular injection, and one or more maintenance doses of rilpivirine or its pharmaceutically acceptable salt are administered as 600 mg intramuscular injection. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days. In some embodiments, one or more maintenance doses are administered once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days, followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times.

[0101] In some embodiments, people in the weight interval of 35 kg to less than 40 kg further administer an oral introduction dose. Therefore, in some embodiments, the method or use further includes orally administering a dosage of cartegravir or its pharmaceutically acceptable salt and rilpivirine or its pharmaceutically acceptable salt before the loading dose, wherein the dosage of cartegravir or its pharmaceutically acceptable salt is a once-daily dosage of 30 mg acid equivalents, and the dosage of rilpivirine is a once-daily dosage of 25 mg base equivalents. In some embodiments, the dosage of cartegravir or its pharmaceutically acceptable salt and rilpivirine or its pharmaceutically acceptable salt is administered once daily for at least 4 weeks, particularly once daily for 4 weeks. In some embodiments, the dosage of cartegravir or its pharmaceutically acceptable salt is in the form of cartegravir sodium. In some embodiments, the dosage of rilpivirine or its pharmaceutically acceptable salt is provided by a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0102] In some embodiments, the human body weight interval is 25 kg to 34.9 kg, and cartegravir or its pharmaceutically acceptable salt is administered as 200 mg to 300 mg intramuscular injection, and rilpivirine or its pharmaceutically acceptable salt is administered as 450 mg to 600 mg intramuscular injection. In some embodiments, the human body weight is 25 kg to 34.9 kg, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 300 mg intramuscular injection, and the loading dose of rilpivirine or its pharmaceutically acceptable salt is administered as 600 mg intramuscular injection. In some embodiments, the human body weight is 25 kg to 34.9 kg, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or its pharmaceutically acceptable salt are administered as 450 mg intramuscular injection. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days. In some embodiments, one or more maintenance doses are administered once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days, followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times.

[0103] In some embodiments, people in the weight range of 25 kg to 34.9 kg further administer an oral introduction dose. Therefore, in some embodiments, the method or use further includes orally administering an introduction dose of cartegravir or its pharmaceutically acceptable salt and rilpivirine or its pharmaceutically acceptable salt before the loading dose, wherein the introduction dose of cartegravir or its pharmaceutically acceptable salt is a once-daily dose of 10 mg acid equivalents, and the introduction dose of rilpivirine is a once-daily dose of 25 mg base equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt and rilpivirine or its pharmaceutically acceptable salt is administered once a day for at least 4 weeks, particularly once a day for 4 weeks. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is administered in two dispersible tablets of 5 mg acid equivalents. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is administered in a tablet of 25 mg base equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is in the form of cartegravir sodium. In some embodiments, the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0104] In some embodiments, the human body weight interval is 20 kg to 24.9 kg, and cartegravir or its pharmaceutically acceptable salt is administered as 200 mg to 300 mg intramuscular injection, and rilpivirine or its pharmaceutically acceptable salt is administered as 450 mg to 600 mg intramuscular injection. In some embodiments, the human body weight is 20 kg to 24.9 kg, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 300 mg intramuscular injection, and the loading dose of rilpivirine or its pharmaceutically acceptable salt is administered as 600 mg intramuscular injection. In some embodiments, the human body weight is 20 kg to 24.9 kg, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or its pharmaceutically acceptable salt are administered as 450 mg intramuscular injection. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days. In some embodiments, one or more maintenance doses are administered once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days, followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times.

[0105] In some embodiments, people in the weight range of 20 kg to 24.9 kg further administer an oral introduction dose. Therefore, in some embodiments, the method or use further includes orally administering an introduction dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof before the loading dose, wherein the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents, and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalents. In some embodiments, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is administered once daily for at least 4 weeks, particularly once daily for 4 weeks. In some embodiments, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is administered in two dispersible tablets of 5 mg acid equivalents. In some embodiments, the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered in six tablets of 2.5 mg base equivalents, preferably in tablets dispersed in a liquid. In some embodiments, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is in the form of cartegravir sodium. In some embodiments, the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0106] In some embodiments, the human body weight range is 14 kg to 19.9 kg, and cartegravir or its pharmaceutically acceptable salt is administered as 200 mg to 300 mg intramuscular injection, and rilpivirine or its pharmaceutically acceptable salt is administered as 300 mg to 450 mg intramuscular injection. In some embodiments, the human body weight is 14 kg to 19.9 kg, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 300 mg intramuscular injection, and the loading dose of rilpivirine or its pharmaceutically acceptable salt is administered as 450 mg intramuscular injection. In some embodiments, the human body weight is 14 kg to 19.9 kg, one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or its pharmaceutically acceptable salt are administered as 300 mg intramuscular injection. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days. In some embodiments, one or more maintenance doses are administered once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days, followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times.

[0107] In some embodiments, people in the weight range of 14 kg to 19.9 kg further administer an oral introduction dose. Therefore, in some embodiments, the method or use further includes orally administering an introduction dose of cartegravir or its pharmaceutically acceptable salt and rilpivirine or its pharmaceutically acceptable salt before the loading dose, wherein the introduction dose of cartegravir or its pharmaceutically acceptable salt is a once-daily dose of 10 mg acid equivalents, and the introduction dose of rilpivirine or its pharmaceutically acceptable salt is a once-daily dose of 12.5 mg base equivalents. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt and rilpivirine or its pharmaceutically acceptable salt is administered once a day for at least 4 weeks, particularly once a day for 4 weeks. In some embodiments, the introduction dose of cartegravir or its pharmaceutically acceptable salt is administered in two dispersible tablets of 5 mg acid equivalents. In some embodiments, the introduction dose of rilpivirine or its pharmaceutically acceptable salt is administered in five tablets of 2.5 mg base equivalents, preferably in tablets dispersed in a liquid. In some embodiments, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is in the form of cartegravir sodium. In some embodiments, the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0108] In some embodiments, the human body weight interval is 10 kg to 13.9 kg, and cartegravir or its pharmaceutically acceptable salt is administered as 200 mg to 300 mg intramuscular injection, and rilpivirine or its pharmaceutically acceptable salt is administered as 300 mg to 450 mg intramuscular injection. In some embodiments, the human body weight is 10 kg to 13.9 kg, the loading dose of cartegravir or its pharmaceutically acceptable salt is administered as 300 mg intramuscular injection, and the loading dose of rilpivirine or its pharmaceutically acceptable salt is administered as 450 mg intramuscular injection. In some embodiments, the human body weight is 10 kg to 13.9 kg, and one or more maintenance doses of cartegravir or its pharmaceutically acceptable salt are administered as 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or its pharmaceutically acceptable salt are administered as 300 mg intramuscular injection. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days. In some embodiments, one or more maintenance doses are administered once every 4 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every two months ± 7 days. In some embodiments, one or more maintenance doses are administered once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once a month ± 7 days or once every 4 weeks ± 7 days, followed by administration once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 times.

[0109] In some embodiments, people in the weight range of 10 kg to 13.9 kg are further administered an oral introduction dose. Therefore, in some embodiments, the method or use further includes oral administration of a dosage of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof before the loading dose, wherein the dosage of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dosage of 10 mg acid equivalents, and the dosage of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dosage of 12.5 mg base equivalents. In some embodiments, the dosage of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is administered once daily for at least 4 weeks, particularly once daily for 4 weeks. In some embodiments, the dosage of cartegravir or a pharmaceutically acceptable salt thereof is administered in two dispersible tablets of 5 mg acid equivalents. In some embodiments, the dosage of rilpivirine or a pharmaceutically acceptable salt thereof is administered in five tablets of 2.5 mg base equivalents, preferably in tablets dispersed in a liquid. In some embodiments, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is in the form of cartegravir sodium. In some embodiments, the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine. In some embodiments, the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0110] In some embodiments, the present disclosure provides a method of treating HIV infection, the method comprising: administering to a human in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; and thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; wherein the age of the human is from 2 years to less than 12 years; and wherein: (a) the weight of the human is from 35 kg to less than 40 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 900 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 400 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 600 mg intramuscular injection; mg intramuscular injection; (b) the human body weight is 25 kg to 34.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection; (c) the human body weight is 20 kg to 24.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection; mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection; (d) the human weighs 14 kg to 19.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection; or (e) the human weighs 10 kg to 13.9 kg; a loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection. .

[0111] In some embodiments, the human is further administered an oral introduction dose. Thus, in some embodiments, the method further comprises orally administering an introduction dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof before the loading dose, wherein (a) if the human has a body weight of 35 kg to less than 40 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalents; (b) if the human has a body weight of 25 kg to 34.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalents; (c) if the human has a body weight of 20 kg to 24.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalents. (d) if the body weight of the human is 14 kg to 19.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalents; or (e) if the body weight of the human is 10 kg to 13.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalents.

[0112] In some embodiments, the present disclosure provides a use of a loading dose and one or more maintenance doses in the preparation of a medicament for treating HIV infection in a human, the loading dose comprising (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof; the maintenance dose comprising (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof; wherein the age of the human is from 2 years old to less than 12 years old; wherein the medicament is formulated for intramuscular injection; and wherein: (a) the weight of the human is from 35 kg to less than 40 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 900 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 400 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection; (b) the weight of the human is from 25 kg to 34.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; (c) the human body weight is 20 kg to 24.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; (d) the human body weight is 14 kg to 19.9 kg; a loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection and a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection; or (e) the human weighs 10 kg to 13.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection. .

[0113] In some embodiments, the present disclosure provides a loading dose and one or more maintenance doses for treating HIV infection in a human, the loading dose comprising (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof; the one or more maintenance doses comprising (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof; wherein the age of the human is from 2 years to less than 12 years; wherein cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for intramuscular injection; and wherein: (a) the weight of the human is from 35 kg to less than 40 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 900 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 400 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection; mg intramuscular injection; (b) the human body weight is 25 kg to 34.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; (c) the human body weight is 20 kg to 24.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; (d) the human body weight is 14 kg to 19.9 kg; a loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection and a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection; or (e) the person weighs 10 kg to 13.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 450 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof is 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection. .

[0114] In some embodiments, the present disclosure provides cartegravir or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with rilpivirine or a pharmaceutically acceptable salt thereof for treating HIV infection in a human; wherein the age of the human is 2 years to less than 12 years; and wherein: (a) the human weighs 35 kg to less than 40 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection; (b) the human weighs 25 kg to 34.9 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection; (c) the human weighs 20 kg to 24.9 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection; (d) the human weighs 14 kg to 19.9 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection; or (e) the human weighs 10 kg to 13.9 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection.

[0115] In some embodiments, the present disclosure provides cartegravir or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with rilpivirine or a pharmaceutically acceptable salt thereof for treating HIV infection in a human; wherein the age of the human is 2 years to less than 12 years; and wherein: (a) the human weighs 35 kg to less than 40 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 400 mg intramuscular injection; (b) the human weighs 25 kg to 34.9 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection; (c) the human weighs 20 kg to 24.9 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection; (d) the human weighs 14 kg to 19.9 kg; and cartegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection; or (e) the human weighs 10 kg to 13.9 kg; and catategravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection.

[0116] In some embodiments, the present disclosure provides rilpivirine or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with cartegravir or a pharmaceutically acceptable salt thereof for treating HIV infection in a human; wherein the age of the human is 2 years to less than 12 years; and wherein: (a) the human weighs 35 kg to less than 40 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 900 mg intramuscular injection; (b) the human weighs 25 kg to 34.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection; (c) the human weighs 20 kg to 24.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection; (d) the human weighs 14 kg to 19.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection; or (e) the human weighs 10 kg to 13.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection.

[0117] In some embodiments, the present disclosure provides rilpivirine or a pharmaceutically acceptable salt thereof, which is indicated for use in combination with cartegravir or a pharmaceutically acceptable salt thereof for treating HIV infection in a human; wherein the age of the human is 2 years to less than 12 years; and wherein: (a) the human weighs 35 kg to less than 40 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection; (b) the human weighs 25 kg to 34.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection; (c) the human weighs 20 kg to 24.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection; (d) the human weighs 14 kg to 19.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection; or (e) the human weighs 10 kg to 13.9 kg; and rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection.

[0118] In some embodiments, the use further comprises an oral introduction dose. Therefore, in some embodiments, the use further comprises an oral introduction dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof before the loading dose, wherein (a) if the body weight of the person is 35 kg to less than 40 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalents, and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalents; (b) if the body weight of the person is 25 kg to 34.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents, and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalents; (c) if the body weight of the person is 20 kg to 24.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents, and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalents. (d) if the body weight of the human is 14 kg to 19.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalents; or (e) if the body weight of the human is 10 kg to 13.9 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalents.

[0119] Numbered implementation plan

[0120] Embodiment 1. A method for treating HIV infection, the method comprising:

[0121] administering to a person in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; and

[0122] thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof;

[0123] The age of the person is between 2 and less than 12 years old.

[0124] Embodiment 2. The method of embodiment 1, wherein the human has a body weight of 10 kg to less than 40 kg, preferably 10 kg to 34.9 kg.

[0125] Embodiment 3. The method of embodiment 1 or 2, wherein the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof.

[0126] Embodiment 4. The method of any one of the preceding embodiments, wherein the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof.

[0127] Embodiment 5. The method of any one of the preceding embodiments, wherein cartegravir or a pharmaceutically acceptable salt thereof is administered as a 50 mg to 600 mg intramuscular injection, preferably as a 100 mg to 600 mg intramuscular injection, a 150 mg to 600 mg intramuscular injection, a 200 mg to 600 mg intramuscular injection, a 300 mg to 600 mg intramuscular injection, or a 200 mg to 400 mg intramuscular injection.

[0128] Embodiment 6. The method of any one of the preceding embodiments, wherein rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg to 900 mg intramuscular injection, preferably as a 100 mg to 900 mg intramuscular injection, a 150 mg to 900 mg intramuscular injection, a 200 mg to 900 mg intramuscular injection, a 250 mg to 900 mg intramuscular injection, a 300 mg to 900 mg intramuscular injection, a 450 mg to 900 mg intramuscular injection, or a 300 mg to 600 mg intramuscular injection.

[0129] Embodiment 7. The method according to any one of the preceding embodiments, wherein one or more maintenance doses are administered at fixed intervals.

[0130] Embodiment 8. The method according to any one of the preceding embodiments, wherein one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently.

[0131] Embodiment 9. The method of embodiment 8, wherein the one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days.

[0132] Embodiment 10. The method of embodiment 9, wherein the one or more maintenance doses are administered once per month ± 7 days.

[0133] Embodiment 11. The method of embodiment 9, wherein one or more maintenance doses are administered once every 4 weeks ± 7 days.

[0134] Embodiment 12. The method of embodiment 8, wherein one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days.

[0135] Embodiment 13. The method of embodiment 12, wherein one or more maintenance doses are administered every two months ± 7 days.

[0136] Embodiment 14. The method of embodiment 12, wherein one or more maintenance doses are administered every 8 weeks ± 7 days.

[0137] Embodiment 15. The method of embodiment 8, wherein the one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days, followed by once every two months ± 7 days or once every 8 weeks ± 7 days.

[0138] Embodiment 16. The method of embodiment 15, wherein one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days.

[0139] Embodiment 17. The method of embodiment 1, wherein the human weighs 35 kg to less than 40 kg, cartegravir or a pharmaceutically acceptable salt thereof is administered as a 400 mg to 600 mg intramuscular injection, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg to 900 mg intramuscular injection.

[0140] Embodiment 18. The method of Embodiment 17, wherein the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 900 mg intramuscular injection.

[0141] Embodiment 19. The method of embodiment 18, wherein the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 400 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 600 mg intramuscular injection.

[0142] Embodiment 20. The method of embodiment 1, wherein the human weighs 25 kg to 34.9 kg, cartegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg to 300 mg intramuscular injection, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 to 600 mg intramuscular injection.

[0143] Embodiment 21. The method of Embodiment 20, wherein the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection.

[0144] Embodiment 22. The method of Embodiment 21, wherein the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection.

[0145] Embodiment 23. The method of embodiment 1, wherein the human weighs 20 kg to 24.9 kg, cartegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg to 300 mg intramuscular injection, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg to 600 mg intramuscular injection.

[0146] Embodiment 24. The method of Embodiment 23, wherein the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection.

[0147] Embodiment 25. The method of Embodiment 24, wherein the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection.

[0148] Embodiment 26. The method of embodiment 1, wherein the human weighs 14 kg to 19.9 kg, cartegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg to 300 mg intramuscular injection, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 450 mg intramuscular injection.

[0149] Embodiment 27. The method of Embodiment 26, wherein the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection.

[0150] Embodiment 28. The method of Embodiment 27, wherein the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection.

[0151] Embodiment 29. The method of embodiment 1, wherein the human weighs 10 kg to 13.9 kg, cartegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg to 300 mg intramuscular injection, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 450 mg intramuscular injection.

[0152] Embodiment 30. The method of Embodiment 29, wherein the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection.

[0153] Embodiment 31. The method of Embodiment 30, wherein the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection.

[0154] Embodiment 32. The method of any one of embodiments 17 to 31, wherein one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently.

[0155] Embodiment 33. The method of embodiment 32, wherein the one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days.

[0156] Embodiment 34. The method of embodiment 33, wherein the one or more maintenance doses are administered once per month ± 7 days.

[0157] Embodiment 35. The method of embodiment 33, wherein one or more maintenance doses are administered once every 4 weeks ± 7 days.

[0158] Embodiment 36. The method of embodiment 32, wherein the one or more maintenance doses are administered once every two months ± 7 days or once every 8 weeks ± 7 days.

[0159] Embodiment 37. The method of embodiment 36, wherein one or more maintenance doses are administered every two months ± 7 days.

[0160] Embodiment 38. The method of embodiment 36, wherein one or more maintenance doses are administered every 8 weeks ± 7 days.

[0161] Embodiment 39. The method of any one of embodiments 19, 22, 25, 28 or 31, wherein the one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days, followed by once every two months ± 7 days or once every 8 weeks ± 7 days.

[0162] Embodiment 40. The method of embodiment 39, wherein one or more maintenance doses are administered once per month ± 7 days or once every 4 weeks ± 7 days for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 times, followed by once every two months ± 7 days or once every 8 weeks ± 7 days.

[0163] Embodiment 41. The method according to any one of the preceding embodiments, wherein the loading dose of cartegravir or a pharmaceutically acceptable salt thereof and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof are administered less than 1 hour apart, preferably less than 30 minutes apart.

[0164] Embodiment 42. The method of any one of the preceding embodiments, wherein for each maintenance dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof, the administration interval of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is less than 1 hour, preferably less than 30 minutes apart.

[0165] Embodiment 43. The method according to any one of the preceding embodiments, wherein the intramuscular injection is administered at a site selected from the gluteus medius or the lateral thigh.

[0166] Embodiment 44. The method according to any one of the preceding embodiments, wherein the injection of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is in the form of a long-acting preparation.

[0167] Embodiment 45. The method of Embodiment 44, wherein the long-acting formulation of cartegravir or a pharmaceutically acceptable salt thereof comprises cartegravir or a pharmaceutically acceptable salt thereof, polysorbate and polyethylene glycol.

[0168] Embodiment 46. The method of embodiment 44 or 45, wherein the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof comprises rilpivirine or a pharmaceutically acceptable salt thereof and a poloxamer.

[0169] Embodiment 47. The method of any one of the preceding embodiments, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose.

[0170] Embodiment 48. The method of embodiment 47, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is 5 mg to 30 mg acid equivalent daily dose, preferably 10 mg to 30 mg acid equivalent daily dose.

[0171] Embodiment 49. The method of embodiment 48, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg to 25 mg base equivalents, preferably a daily dose of 12.5 mg to 25 mg base equivalents.

[0172] Embodiment 50. The method of any one of Embodiments 17 to 19, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 30 mg acid equivalents and the lead-in dose of rilpivirine is a once daily dose of 25 mg base equivalents.

[0173] Embodiment 51. The method of embodiment 50, wherein the introduction doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least 4 weeks, in particular once daily for 4 weeks.

[0174] Embodiment 52. The method of embodiment 50 or 51, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0175] Embodiment 53. The method of Embodiment 52, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0176] Embodiment 54. The method of any one of Embodiments 20 to 22, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the lead-in dose of rilpivirine is a once daily dose of 25 mg base equivalents.

[0177] Embodiment 55. The method of embodiment 54, wherein the introduction doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least 4 weeks, in particular once daily for 4 weeks.

[0178] Embodiment 56. The method of embodiment 54 or 55, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0179] Embodiment 57. The method of any one of Embodiments 54 to 56, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0180] Embodiment 58. The method of Embodiment 57, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0181] Embodiment 59. The method of any one of Embodiments 23 to 25, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the lead-in dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 15 mg base equivalents.

[0182] Embodiment 60. The method of embodiment 59, wherein the introduction doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least 4 weeks, in particular once daily for 4 weeks.

[0183] Embodiment 61. The method of embodiment 59 or 60, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0184] Embodiment 62. The method of any one of Embodiments 59 to 61, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as six 2.5 mg base equivalent tablets, preferably as tablets dispersed in a liquid.

[0185] Embodiment 63. The method of any one of Embodiments 59 to 62, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0186] Embodiment 64. The method of Embodiment 63, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0187] Embodiment 65. The method of any one of Embodiments 26 to 28, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the lead-in dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 12.5 mg base equivalents.

[0188] Embodiment 66. The method of embodiment 65, wherein the introduction doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least 4 weeks, in particular once daily for 4 weeks.

[0189] Embodiment 67. The method of embodiment 65 or 66, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0190] Embodiment 68. The method of any one of Embodiments 65 to 67, wherein the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as five 2.5 mg base equivalent tablets, preferably as tablets dispersed in a liquid.

[0191] Embodiment 69. The method of any one of Embodiments 65 to 68, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0192] Embodiment 70. The method of Embodiment 69, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0193] Embodiment 71. The method of any one of Embodiments 29 to 31, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the lead-in dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 12.5 mg base equivalents.

[0194] Embodiment 72. The method of embodiment 71, wherein the introduction doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least 4 weeks, in particular once daily for 4 weeks.

[0195] Embodiment 73. The method of embodiment 71 or 72, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0196] Embodiment 74. The method of any one of Embodiments 71 to 73, wherein the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as five 2.5 mg base equivalent tablets, preferably as tablets dispersed in a liquid.

[0197] Embodiment 75. The method of any one of Embodiments 71 to 74, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0198] Embodiment 76. The method of Embodiment 75, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0199] Embodiment 77. The method of any one of Embodiments 47 to 76, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more dispersible tablets.

[0200] Embodiment 78. The method of any one of Embodiments 47 to 77, wherein the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more tablets dispersed in a liquid.

[0201] Embodiment 79. The method of any one of Embodiments 47 to 78, wherein the introduction doses of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered with food.

[0202] Embodiment 80. The method of any one of the preceding embodiments, wherein prior to initiating treatment, the human exhibits a viral load of less than or equal to 50 copies of HIV-1 RNA per mL of plasma.

[0203] Embodiment 81. The method of any one of the preceding embodiments, wherein after at least 72 weeks of treatment, the human exhibits a viral load of less than or equal to 50 copies of HIV-1 RNA per mL of plasma.

[0204] Embodiment 82. A method of treating HIV infection, the method comprising:

[0205] administering to a person in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; and

[0206] thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof;

[0207] where the person is between 2 and under 12 years old; and

[0208] in:

[0209] (a) the human weighs 35 kg to less than 40 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 900 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 400 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 600 mg intramuscular injection;

[0210] (b) the human weighs 25 kg to 34.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection;

[0211] (c) the human weighs 20 kg to 24.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection;

[0212] (d) the human weighs 14 kg to 19.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection; or

[0213] (e) the human weighs 10 kg to 13.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection.

[0214] Embodiment 83. The method of embodiment 82, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein

[0215] (a) if the human body weight is 35 kg to less than 40 kg, the introduction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 30 mg acid equivalents and the introduction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 25 mg base equivalents;

[0216] (b) if the human body weight is 25 kg to 34.9 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 25 mg base equivalents;

[0217] (c) if the human body weight is 20 kg to 24.9 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 15 mg base equivalents;

[0218] (d) if the person weighs 14 kg to 19.9 kg, the induction dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 12.5 mg base equivalents; or

[0219] (e) if the human body weight is 10 kg to 13.9 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalent, and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 12.5 mg base equivalent.

[0220] Embodiment 84. Use of (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating HIV infection in a human, wherein the human is aged from 2 years to less than 12 years, and the medicament is formulated for regular intramuscular injection.

[0221] Embodiment 85. Cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are used to treat HIV infection in a human, wherein the human is aged from 2 years to less than 12 years, and cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for regular intramuscular injection.

[0222] Embodiment 86. Cartegravir or a pharmaceutically acceptable salt thereof, indicated for use in combination with rilpivirine or a pharmaceutically acceptable salt thereof for treating HIV infection in a human, wherein the human is 2 years of age to less than 12 years of age, and the cartegravir or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection.

[0223] Embodiment 87. Rilpivirine or a pharmaceutically acceptable salt thereof, indicated for use in combination with cartegravir or a pharmaceutically acceptable salt thereof for treating HIV infection in a human, wherein the human is 2 years of age to less than 12 years of age, and the rilpivirine or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection.

[0224] It should be understood that any and all embodiments of the present disclosure can be combined with any other embodiment or embodiments to describe additional more preferred embodiments. It should also be understood that each individual element of the preferred embodiment is its own independent preferred embodiment. In addition, any element of the embodiment is intended to be combined with any and all other elements in any embodiment to describe additional embodiments. Example

[0225] Example 1: Phase I / II trial of CAB LA and RPV LA in children.

[0226] Study design.

[0227] The Phase I / II, multicenter, open-label, noncomparative study will evaluate the safety, tolerability, acceptability, and PK of an oral CAB and oral RPV followed by a long-acting injectable CAB (CAB LA) and a long-acting injectable RPV (RPV LA) for dosing by weight interval in virologically suppressed children aged 2 years to less than 12 years infected with HIV-1. The study will also evaluate the long-acting injectable regimen with and without an oral lead-in period in the same study population. CAB LA is formulated as a suspension containing 200 mg / mL of cartegravir free acid for administration by IM injection. RPV LA is formulated as a suspension containing 300 mg / mL of RPV free base for administration by IM injection.

[0228] This study will be conducted in up to 90 children weighing ≥10 kg and <40 kg who are virologically suppressed on stable ART. Parents / guardians of approximately 90 child participants will also be enrolled to complete tolerability and acceptability assessments. In-depth qualitative interviews will also be conducted with a subset of enrolled parents / guardians. Unless otherwise specified, the term "participant" will refer to the child enrolled in the study.

[0229] The study will include two cohorts.

[0230] In Cohort 1, participants will be enrolled into the following five weight intervals: weight interval 1 (35-<40 kg), weight interval 2 (25-34.9 kg), weight interval 3 (20-24.9 kg), weight interval 4 (14-19.9 kg), and weight interval 5 (10-13.9 kg).

[0231] Once enrolled in Group 1, participants in each weight interval will go through two study participation steps. In Step 1 (i.e., when entering the study), participants will switch from their pre-study ART regimen to oral formulations of daily CAB and oral formulations of RPV, for at least four weeks and up to a maximum of six weeks. According to the 4a week visit, participants who meet the eligibility criteria will transition to Step 2 and receive injectable CAB LA + injectable RPV LA to Week 72. Participants who prematurely and permanently stop oral CAB + RPV or do not meet the eligibility criteria for the injection phase will exit the study 28 days after their last oral study product administration. In Step 2, participants will receive injectable CAB LA + RPV LA. Two IM injections (one CAB LA injection and one RPV LA injection) will be administered at the 4b week (entering Step 2) visit, at the 8th week visit, and then every four weeks or every eight weeks thereafter (depending on the recommendations of the 12th week interim analysis), and the last injection will be administered at the 72nd week visit. During both steps, participants will follow the dosing regimen outlined in the Product Regimen section below.

[0232] Cohort 2 will consist of two groups (i.e., Cohort 2a and Cohort 2b), which will allow participants to choose between regimens that include and do not include oral introduction. Participants enrolled in Cohort 2a will progress through two study participation steps, as described above for Cohort 1. Participants in Cohort 2a will receive oral CAB + oral RPV (Step 1) until the Week 4b visit, and then receive intramuscular doses of CAB LA and injectable doses of RPVLA from Week 4b (entering Step 2) to Week 48, based on the relevant weight interval dosing regimen recommended at that time. Participants enrolled in Cohort 2b will skip the oral introduction phase and receive CAB LA and RPV LA upon entry into the study and continue until Week 44, based on the relevant weight interval dosing regimen recommended at that time.

[0233] The decision to join Cohort 2a or Cohort 2b will be made by the potential study participant and / or parent / legal guardian in consultation with the investigator of record or designee and other health care providers, as applicable. This choice will be made as part of the informed consent or assent process and must be confirmed prior to study entry; participants may not change their Cohort 2a or Cohort 2b group selection after enrollment.

[0234] Product solutions.

[0235] At entry, all participants will discontinue their pre-study cART regimen and will be assigned a dosing regimen based on their weight at entry into the respective cohort. Weight-based dose adjustments will be made according to the guidance provided in the Dose Modifications section below. The dosing regimen may be modified based on the Cohort 1 interim analysis or based on experience in the study, in which case the new regimen will be detailed in the Dosing Regimen Modifications section below.

[0236] Cohort 1 participants will receive oral CAB and oral RPV followed by intramuscular CAB LA and intramuscular RPV LA as shown in Table 1 (for oral dosing) and Table 2 (for LA injection).

[0237] Participants in Cohort 2a will receive oral CAB and oral RPV followed by intramuscular CAB LA and intramuscular RPV LA. Participants in Cohort 2b will receive only intramuscular CAB LA and intramuscular RPV LA.

[0238] Table 1. Cohort 1: Initial oral introduction dosing regimen

[0239]

[0240] Table 2. Cohort 1: Initial (Q4W) IM injection dosing regimen

[0241]

[0242] Based on modeling and analysis of previous data, the initial dose for each weight interval was determined, and the oral and long-acting regimens for the initial doses recommended in Tables 1 and 2 were calculated to achieve plasma concentrations within the acceptable range observed clinically in adolescents and adults.

[0243] Dosage adjustments.

[0244] The participant's weight at the Entry Visit will determine the participant's weight zone and assigned oral dose for the entire duration of the Oral Run-in Phase. The oral dose will not be adjusted for changes in weight zone (weight gain or loss) that may occur during the Oral Run-in Phase.

[0245] At each injection visit, prior to administration of study product, the participant's weight will be assessed to determine the appropriate weight range and injectable dosing regimen to be administered at that visit. Participants who move up a weight range will begin the dosing regimen that corresponds to their new applicable weight range. However, a decrease in weight range will not result in a change in dosing; participants will continue on the dosing regimen for the highest weight range achieved.

[0246] Modification of dosing regimen.

[0247] The dosing regimen for each weight range may be modified as needed following the interim analysis of Cohort 1 and / or based on ongoing review of safety, PK, viral load, tolerability and all other relevant data in the study or other ongoing studies of the study drug in the pediatric population. The dose modification and initial dose for Cohort 2 as mentioned above will be selected from Tables 3 to 8. Currently enrolled and newly enrolled participants will be assigned to the updated dosing regimen.

[0248] If the injection schedule is changed from Q4W to Q8W dosing, enrolled participants who are still in the oral run-in phase can receive injections on a Q8W schedule. Enrolled participants who have started injections on a Q4W schedule and have completed the Week 12 visit will continue to receive injections on a Q4W schedule until the Week 24 (Cohort 1 and Cohort 2a) or Week 20 (Cohort 2b) visit.

[0249] Regardless of how the dosing regimen is modified, it is expected that each dosing regimen will include (where applicable) the daily oral doses of cartegravir and rilpivirine shown in Tables 3 and 4, the injectable CAB LA + RPV LA doses shown in Tables 5, 6, 7 and 8, and the injection intervals shown in Table 9.

[0250] Table 3: CAB oral dosage

[0251]

[0252] Table 4: RPV oral dosage

[0253]

[0254] Table 5: CAB LA first injection dose

[0255]

[0256] Table 6: CAB LA follow-up injections

[0257]

[0258] Table 7: RPV LA first injection dose

[0259]

[0260] Table 8: RPV LA follow-up injection dose

[0261]

[0262] Table 9: Injection intervals

[0263]

[0264] Oral bridging for participants receiving LA injection

[0265] In some cases, participants who miss a scheduled injection may receive daily oral CAB + RPV as a bridging strategy. The oral study product weight interval dosing regimen will be assigned based on the participant's weight obtained at the most recent study visit (either a regularly scheduled visit or an interim visit).

[0266] Ideally, participants should start the oral bridging regimen on the same target visit day (or within the same target visit window) as the missed injection visit day. The last dose of the short-term oral bridging regimen should be taken on the same day as and before the resumption of the injectable study product. Step 2 Participants may need to have an interim injection visit after resuming study product injections to appropriately restart the dosing regimen or realign the dosing schedule with the original injection visit.

Claims

1. A method for treating HIV infection, the method comprising: administering to a person in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; as well as thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; The age of the person is from 2 to less than 12 years old.

2. The method of claim 1, wherein the human has a body weight of 10 kg to less than 40 kg, preferably 10 kg to 34.9 kg.

3. The method of any one of the preceding claims, wherein the cartegravir or a pharmaceutically acceptable salt thereof is administered as a 50 mg to 600 mg intramuscular injection, preferably as a 100 mg to 600 mg intramuscular injection, 150 mg to 600 mg intramuscular injection, 200 mg to 600 mg intramuscular injection, 300 mg to 600 mg intramuscular injection or 200 mg to 400 mg intramuscular injection, and the rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg to 900 mg intramuscular injection, preferably as a 100 mg to 900 mg intramuscular injection, 150 mg to 900 mg intramuscular injection, 200 mg to 900 mg intramuscular injection, 250 mg to 900 mg intramuscular injection, 300 mg to 900 mg intramuscular injection, 450 mg to 900 mg intramuscular injection, or 300 mg to 600 mg intramuscular injection.

4. The method of any of the preceding claims, wherein the one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently.

5. The method according to any one of the preceding claims, wherein the injection of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is in the form of a long-acting preparation.

6. The method of any one of the preceding claims, wherein the injection of cartegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the cartegravir or a pharmaceutically acceptable salt thereof is in a free acid / base form; and the injection of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the rilpivirine or a pharmaceutically acceptable salt thereof is in a free base form.

7. The method of any one of the preceding claims, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose.

8. The method of claim 7, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is 5 mg to 30 mg acid equivalents per day, preferably 10 mg to 30 mg acid equivalents per day, and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is 2.5 mg to 25 mg base equivalents per day, preferably 12.5 mg to 25 mg base equivalents per day.

9. The method of claim 7 or 8, wherein the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more dispersible tablets, and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more tablets dispersed in a liquid.

10. The method of any one of claims 7 to 9, wherein the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine, preferably wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

11. A method for treating HIV infection, the method comprising: administering to a person in need thereof a loading dose comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; as well as thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cartegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; wherein the person is between 2 and less than 12 years old; and in: (a) the human has a body weight of 35 kg to less than 40 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 900 mg intramuscular injection; and one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 400 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 600 mg intramuscular injection; (b) the human has a body weight of 25 kg to 34.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection; (c) the human has a body weight of 20 kg to 24.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 450 mg intramuscular injection; (d) the human has a body weight of 14 kg to 19.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection; or (e) the human has a body weight of 10 kg to 13.9 kg; the loading dose of cartegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection; and the one or more maintenance doses of cartegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg intramuscular injection, and the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are administered as a 300 mg intramuscular injection.

12. The method of claim 11, further comprising orally administering a lead-in dose of cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein (a) if the human body weight is 35 kg to less than 40 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalent, and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent; (b) if the human body weight is 25 kg to 34.9 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent, and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent; (c) if the human body weight is 20 kg to 24.9 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent, and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalent; (d) if the human has a body weight of 14 kg to 19.9 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalents and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 12.5 mg base equivalents; or (e) if the human body weight is 10 kg to 13.9 kg, the introduced dose of cartegravir or a pharmaceutically acceptable salt thereof is a once daily dose of 10 mg acid equivalent, and the introduced dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once daily dose of 12.5 mg base equivalent.

13. Use of (i) cartegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating HIV infection in a human, wherein the human is aged from 2 years to less than 12 years, and the medicament is formulated for regular intramuscular injection.

14. Cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for use in treating HIV infection in a human, wherein the human is aged from 2 years to less than 12 years, and the cartegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for regular intramuscular injection.

15. Cartegravir or a pharmaceutically acceptable salt thereof, indicated for use in combination with rilpivirine or a pharmaceutically acceptable salt thereof for the treatment of HIV infection in a human, wherein the human is between 2 years of age and less than 12 years of age, and the cartegravir or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection.

16. Rilpivirine or a pharmaceutically acceptable salt thereof, indicated for use in combination with cartegravir or a pharmaceutically acceptable salt thereof for the treatment of HIV infection in a human, wherein the human is between 2 years of age and less than 12 years of age, and the rilpivirine or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection.

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