Treatment of HIV in pediatric patients with cabotegravir and rilpivirine

Abstract

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

Description

[Technical Field]

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

[0002] Decades of advances in antiretroviral therapy (ART) have 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 single-pill, once-daily ART regimen. However, viral suppression rates in children are lower than in adults. The lack of pediatric formulations and potent regimens for children contributes to adherence difficulties and low suppression rates. The safety profile of ART has gradually improved, allowing for the inclusion of medications with rare adverse effects and good tolerability in treatment regimens. Despite advances in ART for older adults, few simplified HIV-1 regimens are available for young children. The same obstacles that contribute to poor adherence to pediatric ART have also led to delays in pediatric clinical trials of medications already approved for adults, compounding the obstacles faced by HIV-1-infected children.

[0003] Furthermore, normal weight gain in children requires regular weight-based adjustments in ART dosing, making it difficult to create a single fixed-dose combination containing multiple antiretrovirals that can be adjusted as the child grows. Additionally, small children have difficulty swallowing tablets, necessitating the development of specific drug formulations (i.e., liquids, dispersible tablets, etc.) targeted at this relatively small patient group, further delaying the availability of new medications.

[0004] Cabotegravir (CAB) and rilpivirine (RPV) are the first long-acting (LA) injectable ART approved for the treatment of HIV-1. CAB is a potent integrase strand transfer inhibitor (INSTI) with properties that allow it to be formulated and delivered as a parenteral LA product. RPV, also formulated as an LA product, is a diarylpyrimidine derivative and a potent non-nucleoside reverse transcriptase inhibitor (NNRTI). The combination of CAB LA and RPV LA has an acceptable safety profile and is well-tolerated and effective as a dual injectable ART in virologically suppressed HIV-1-infected adults and adolescents (ages 12 years and older). CABENUVA is a two-drug co-packaged product, cabotegravir and rilpivirine, approved by the U.S. Food and Drug Administration for the treatment of HIV-1 infection in adults and adolescents aged 12 years or older and weighing at least 35 kg who are virologically suppressed on a stable antiretroviral regimen (HIV-1 RNA <50 copies / mL), have no history of treatment failure, and have no known or suspected resistance to either cabotegravir or rilpivirine. Recommended dosing for CABENUVA is monthly or every two months. Summary of the Invention

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

[0006] In one aspect, the disclosure provides a method of treating HIV infection, the method comprising administering a loading dose comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof to a human being in need thereof, followed by administering one or more maintenance doses comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof, wherein the human is between 2 and less than 12 years of age, and (a) the human (b) a human weighing 35 kg to less than 40 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, a 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 cabotegravir 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; (c) a human weighing 25 kg to 34.9 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a 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 cabotegravir 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; or (d) a human weighing 14 kg to 24.9 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a 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 cabotegravir 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; or9 kg, and a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, 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 cabotegravir 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) a human body weight of 1 and wherein the patient's weight is between 0 kg and 13.9 kg, a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection.

[0007] In one aspect, the disclosure provides the use of (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in treating HIV infection in a human, wherein the human is between 2 and under 12 years of age, and the medicament is formulated for regular intramuscular injection.

[0008] In one aspect, the disclosure provides cabotegravir 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 and under 12 years of age, and wherein the cabotegravir 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 disclosure provides cabotegravir or a pharmaceutically acceptable salt thereof, indicated in combination with rilpivirine or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and less than 12 years of age, and the cabotegravir or pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection. In one embodiment, the rilpivirine or pharmaceutically acceptable salt thereof is formulated for intramuscular injection.

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

[0011] The disclosed methods involving the use of LA injectable ART advantageously improve treatment adherence rates compared to existing regimens, thereby enabling HIV-1 infected children to achieve sustained viral suppression. DETAILED DESCRIPTION OF THE INVENTION

[0012] The present disclosure provides a method for treating HIV infection in a pediatric human patient by administering cabotegravir or a pharmaceutically acceptable salt thereof in combination with rilpivirine or a pharmaceutically acceptable salt thereof. The method comprises periodically administering to a pediatric human patient in need thereof (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof. The pediatric human patient is between the ages of 2 and less than 12 years.

[0013] In some embodiments, the human is virally suppressed before initiation of treatment, i.e., exhibits a viral load of HIV-1 RNA of 50 copies or less per mL of plasma, particularly less than 50 copies. In some embodiments, the human exhibits a viral load of HIV-1 RNA of 50 copies or less per mL of plasma after at least 72 weeks of treatment with cabotegravir and rilpivirine, including an optional oral lead to treatment.

[0014] Intramuscular medication In one aspect, the disclosure provides a method of treating HIV infection, the method comprising administering a loading dose comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof to a human being in need thereof, followed by administering one or more maintenance doses comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof, wherein the human is between the ages of 2 and less than 12 years.

[0015] 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 doses are different for patients in different weight ranges, with patients in lighter weight ranges receiving lower doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof than patients in heavier weight ranges.

[0016] In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof, hi 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.

[0017] In some embodiments, cabotegravir or a pharmaceutically acceptable salt thereof is administered 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 600 mg intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg to 600 mg intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg to 600 mg intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg to 400 mg intramuscular injection. In some embodiments, cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg.

[0018] In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 50 mg to 600 mg, preferably as an intramuscular injection of 100 mg to 600 mg, 150 mg to 600 mg, 200 mg to 600 mg, or 300 mg to 600 mg. In one embodiment, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 200 mg to 600 mg. In one embodiment, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg to 600 mg. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg.

[0019] In some embodiments, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are administered as an intramuscular injection of 50 mg to 600 mg, preferably an intramuscular injection of 100 mg to 600 mg, 150 mg to 600 mg, 200 mg to 600 mg, or 200 mg to 400 mg. In one embodiment, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are administered as an intramuscular injection of 200 mg to 600 mg. In one embodiment, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are administered as an intramuscular injection of 200 mg to 400 mg. In some embodiments, the one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are administered as an intramuscular injection of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg.

[0020] In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is administered 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 administered as an intramuscular injection of 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg.

[0021] In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 50 mg to 900 mg, preferably as an intramuscular injection of 100 mg to 900 mg, 150 mg to 900 mg, 200 mg to 900 mg, 250 mg to 900 mg, 450 mg to 900 mg, or 300 mg to 900 mg. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg to 900 mg. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 450 mg to 900 mg. In some embodiments, a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg.

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

[0023] It should be understood that disclosure of amounts (eg, mg) of rilpivirine or a pharmaceutically acceptable salt thereof in injectable form includes the disclosed amount expressed as the base equivalent.

[0024] In some embodiments, the loading doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered 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 cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof, the cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered 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.

[0025] In some embodiments, cabotegravir 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 cabotegravir or a pharmaceutically acceptable salt thereof.

[0026] In some embodiments, the intramuscular injection is administered at a site selected from the gluteus medius muscle or the lateral aspect of the thigh.

[0027] In some embodiments, the intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof 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 cabotegravir or a pharmaceutically acceptable salt thereof is at a concentration of 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 a pharmaceutically acceptable salt thereof 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 a pharmaceutically acceptable salt thereof is at a concentration of 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.

[0028] Interval between intramuscular doses In some embodiments, one or more maintenance doses are administered at regular 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 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every 2 months ± 7 days. In some embodiments, one or more maintenance doses are administered once every 8 weeks ± 7 days.

[0029] In some embodiments, the one or more maintenance doses are administered at regular intervals over a period of time, followed by administration at different, e.g., longer, regular intervals, hi some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four weeks ±7 days, followed by administration once every two months ±7 days or once every eight weeks ±7 days. In some embodiments, one or more maintenance doses are administered 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 once every month ± 7 days or once every 4 weeks ± 7 days (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 given), followed by a maintenance dose once every 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 maintenance doses administered once every two months ±7 days or once every eight 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.

[0030] Oral induction dose In some embodiments, an oral loading dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is administered before the loading dose. Thus, in some embodiments, the method further comprises orally administering a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof before the loading dose.

[0031] In some embodiments, the loading dose of cabotegravir 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 loading 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.

[0032] In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is administered with food.

[0033] In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg to 30 mg acid equivalent, preferably 10 mg to 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 10 mg to 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, or 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 10 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a single tablet with an acid equivalent of 30 mg. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as 1, 2, 3, 4, or 5 5 mg acid equivalent dispersible tablets. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as 2 5 mg acid equivalent dispersible tablets.

[0034] In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg to 25 mg of base equivalent, preferably 12.5 mg to 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 12.5 mg to 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, or 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 12.5 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 15 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 25 mg of base equivalent. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as one 25 mg base equivalent tablet. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as 1, 2, 3, 4, 5, 6, 7, or 8 2.5 mg tablets, preferably as tablets dispersed in a liquid. In some embodiments, the introductory 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 introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as six 2.5 mg tablets, preferably as tablets dispersed in a liquid.

[0035] In some embodiments, the cabotegravir or pharmaceutically acceptable salt thereof in the oral formulation is in the form of cabotegravir sodium. In some embodiments, the rilpivirine or 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.

[0036] Oral bridging dose In some embodiments, an oral bridging dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is administered to a human instead of the scheduled intramuscular injection. Thus, in some embodiments, the method further comprises orally administering a bridging dose, particularly a once-daily bridging dose of cabotegravir or a pharmaceutically acceptable salt thereof and / or rilpivirine or a pharmaceutically acceptable salt thereof, instead of the scheduled intramuscular injection, particularly for a human who is at risk of or has missed a scheduled intramuscular injection. In one embodiment, the first oral bridging dose is administered on the day the intramuscular injection was missed or ±7 days after that day. In one embodiment, the final oral bridging dose is administered on the day, particularly before, when intramuscular injections are to be resumed.

[0037] formulation The injectable formulations of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are in the form of long-acting formulations.

[0038] In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is a suspension formulation, particularly a prolonged-release suspension for injection or an extended-release suspension for injection. In some embodiments, the cabotegravir or pharmaceutically acceptable salt thereof in the long-acting formulation is in the form of cabotegravir free base. In some embodiments, the concentration of cabotegravir or a pharmaceutically acceptable salt thereof in the suspension is 200 mg / mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 400 mg in a volume of 2 mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 600 mg in a volume of 3 mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises cabotegravir or a pharmaceutically acceptable salt thereof, polysorbate, and polyethylene glycol. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises cabotegravir or a pharmaceutically acceptable salt thereof, mannitol, polysorbate (e.g., polysorbate 20 or polysorbate 80), polyethylene glycol (PEG) (e.g., PEG3350), and water for injection. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises 200 mg / mL cabotegravir, 35 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG3350, and water for injection. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises 200 mg / mL cabotegravir, 45 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG3350, and water for injection.

[0039] In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is a suspension formulation, particularly a sustained-release suspension for injection or an extended-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, particularly 300 mg / mL base equivalent. 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 a 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 a 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 to adjust the pH.

[0040] In some embodiments, the injectable formulation of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the cabotegravir or pharmaceutically acceptable salt thereof is in free form (i.e., non-salt form), and the injectable formulation of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the rilpivirine or pharmaceutically acceptable salt thereof is in free form (i.e., non-salt form). In some embodiments, the injectable formulation of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the cabotegravir or pharmaceutically acceptable salt thereof is in the free acid / base form, and the injectable formulation of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the rilpivirine or pharmaceutically acceptable salt thereof is in the free base form.

[0041] Use in treating HIV In one aspect, the disclosure provides the use of (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in treating HIV infection in a human, wherein the human is between the ages of 2 and under 12 years old, and the medicament is formulated for regular intramuscular injection. In one aspect, the disclosure provides the use of a loading dose comprising (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof, and one or more maintenance doses comprising (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in treating HIV infection in a human, wherein the human is between the ages of 2 and under 12 years old, and the loading dose and the one or more maintenance doses are formulated for intramuscular injection. In one aspect, the disclosure provides cabotegravir 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 and under 12 years of age, and wherein the cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine, or a pharmaceutically acceptable salt thereof, are formulated for regular intramuscular injection.

[0042] 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 doses are different for patients in different weight ranges, with patients in lighter weight ranges receiving lower doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof than patients in heavier weight ranges.

[0043] In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is greater than one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof, hi 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.

[0044] In some embodiments, cabotegravir 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, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg to 600 mg intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg to 600 mg intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg to 400 mg intramuscular injection. In some embodiments, cabotegravir 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.

[0045] In some embodiments, the loading dose of cabotegravir 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, or a 300 mg to 600 mg intramuscular injection. In one embodiment, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg to 600 mg intramuscular injection. In one embodiment, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg to 600 mg intramuscular injection. In some embodiments, the loading dose of cabotegravir 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.

[0046] In some embodiments, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are 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, or a 200 mg to 400 mg intramuscular injection. In one embodiment, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are formulated as a 200 mg to 600 mg intramuscular injection. In one embodiment, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are administered as a 200 mg to 400 mg intramuscular injection. In some embodiments, the one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are formulated as an intramuscular injection of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg.

[0047] 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.

[0048] In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as an intramuscular injection of 50 mg to 900 mg, preferably an intramuscular injection of 100 mg to 900 mg, 150 mg to 900 mg, 200 mg to 900 mg, 250 mg to 900 mg, 450 mg to 900 mg, or 300 mg to 900 mg. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg to 900 mg. In one embodiment, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 450 mg to 900 mg. In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as an intramuscular injection of 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg.

[0049] In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are 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, or a 300 mg to 600 mg 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, the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are formulated as an intramuscular injection of 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg.

[0050] It should be understood that disclosure of amounts (eg, mg) of rilpivirine or a pharmaceutically acceptable salt thereof in injectable form includes the disclosed amount expressed as the base equivalent.

[0051] In some embodiments, one or more maintenance doses are formulated for administration at regular intervals. In some embodiments, one or more maintenance doses are formulated for administration once every 4 weeks ± 7 days or less frequently. 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 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once every 2 months ± 7 days. In some embodiments, one or more maintenance doses are formulated for administration once every 8 weeks ± 7 days.

[0052] In some embodiments, the one or more maintenance doses are formulated to be administered at regular intervals over a period of time, followed by administration at different, e.g., longer, regular intervals, hi some embodiments, the one or more maintenance doses are formulated to be administered once every month ±7 days or once every four weeks ±7 days, followed by administration once every two months ±7 days or once every eight weeks ±7 days. In some embodiments, the one or more maintenance doses are administered 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 once every month ± 7 days or once every 4 weeks ± 7 days (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 given), and then formulated to be administered once every 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, the one or more maintenance doses are formulated to be administered once every month ±7 days or once every four 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 eight 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.

[0053] In some embodiments, the pharmaceutical product further comprises an oral loading dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for administration before the loading dose. Thus, in some embodiments, the use further comprises an loading dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof formulated for oral administration before the loading dose.

[0054] In some embodiments, the loading dose of cabotegravir 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 loading 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.

[0055] In some embodiments, the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are formulated for administration with food.

[0056] In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg to 30 mg acid equivalent, preferably 10 mg to 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 10 mg to 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, or 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 10 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is formulated for administration as a single tablet with an acid equivalent of 30 mg. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is formulated for administration as 1, 2, 3, 4, or 5 5 mg acid equivalent dispersible tablets. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is formulated for administration as 2 5 mg acid equivalent dispersible tablets.

[0057] In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg to 25 mg of base equivalent, preferably 12.5 mg to 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 12.5 mg to 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, or 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 12.5 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 15 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 25 mg of base equivalent. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated to be administered as one 25 mg base equivalent tablet.In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated to be administered as 1, 2, 3, 4, 5, 6, 7, or 8 2.5 mg tablets, preferably as tablets dispersed in liquid.In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated to be administered as five 2.5 mg tablets, preferably as tablets dispersed in liquid.In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated to be administered as six 2.5 mg tablets, preferably as tablets dispersed in liquid.

[0058] In some embodiments, the cabotegravir or pharmaceutically acceptable salt thereof in the oral formulation is in the form of cabotegravir sodium. In some embodiments, the rilpivirine or 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.

[0059] In some embodiments, the pharmaceutical product comprises an oral bridging dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof for administration to a human in place of a scheduled intramuscular injection. Thus, in some embodiments, the use further comprises an oral bridging dose, particularly a once-daily oral bridging dose of cabotegravir or a pharmaceutically acceptable salt thereof and / or rilpivirine or a pharmaceutically acceptable salt thereof, in place of a scheduled intramuscular injection, particularly for a human who is at risk of 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 ±7 days after that day. In one embodiment, the final oral bridging dose is provided on the day, particularly before, when intramuscular injections are to be resumed.

[0060] In some embodiments, the medicament is suitable for administration to a human exhibiting a viral load of HIV-1 RNA of 50 copies / mL or less of plasma. In some embodiments, use of the medicament in a human achieves a viral load of HIV-1 RNA of 50 copies / mL or less of plasma after at least 72 weeks.

[0061] In some embodiments, the loading doses of cabotegravir 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. In some embodiments, for each maintenance dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof, the cabotegravir 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.

[0062] In some embodiments, cabotegravir or a pharmaceutically acceptable salt thereof is formulated for administration first, and rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration second. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration first, and cabotegravir or a pharmaceutically acceptable salt thereof is formulated for administration second.

[0063] In some embodiments, the intramuscular injection is formulated for administration to a site selected from the gluteus medius muscle or the lateral aspect of the thigh.

[0064] In some embodiments, the intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof 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 cabotegravir or a pharmaceutically acceptable salt thereof 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 a pharmaceutically acceptable salt thereof 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 a pharmaceutically acceptable salt thereof 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.

[0065] The injectable formulations of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are in the form of long-acting formulations.

[0066] In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is a suspension formulation, particularly a sustained-release suspension for injection or an extended-release suspension for injection. In some embodiments, the concentration of cabotegravir or a pharmaceutically acceptable salt thereof in the suspension is 200 mg / mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 400 mg in a volume of 2 mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 600 mg in a volume of 3 mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises cabotegravir or a pharmaceutically acceptable salt thereof, polysorbate, and polyethylene glycol. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises cabotegravir or a pharmaceutically acceptable salt thereof, mannitol, a polysorbate (e.g., polysorbate 20 or polysorbate 80), polyethylene glycol (PEG) (e.g., PEG3350), and water for injection. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises 200 mg / mL cabotegravir, 35 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG3350, and water for injection. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises 200 mg / mL cabotegravir, 45 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG3350, and water for injection. In some embodiments, the cabotegravir or a pharmaceutically acceptable salt thereof in the long-acting formulation is in the form of cabotegravir free base.

[0067] In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is a suspension formulation, particularly a sustained-release suspension for injection or an extended-release suspension for injection. In some embodiments, the concentration of rilpivirine or a pharmaceutically acceptable salt thereof in the suspension is 300 mg / mL, particularly 300 mg / mL base equivalent. 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 a 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 the 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.

[0068] In some embodiments, the injectable formulation of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the cabotegravir or pharmaceutically acceptable salt thereof is in free form (i.e., non-salt form), and the injectable formulation of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the rilpivirine or pharmaceutically acceptable salt thereof is in free form (i.e., non-salt form). In some embodiments, the injectable formulation of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the cabotegravir or pharmaceutically acceptable salt thereof is in the free acid / base form, and the injectable formulation of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the rilpivirine or pharmaceutically acceptable salt thereof is in the free base form.

[0069] Compositions of Cabotegravir and Rilpivirine In one aspect, the disclosure provides cabotegravir or a pharmaceutically acceptable salt thereof, indicated in combination with rilpivirine or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and under 12 years of age, and the cabotegravir or pharmaceutically acceptable salt thereof is formulated for regular intramuscular injections. In one embodiment, the rilpivirine or pharmaceutically acceptable salt thereof is formulated for regular intramuscular injections. In one aspect, the disclosure provides rilpivirine or a pharmaceutically acceptable salt thereof, indicated in combination with cabotegravir or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and under 12 years of age, and the rilpivirine or pharmaceutically acceptable salt thereof is formulated for regular intramuscular injections. In one embodiment, the cabotegravir or a pharmaceutically acceptable salt thereof is formulated for regular intramuscular injections.

[0070] 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 doses are different for patients in different weight ranges, with lower doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof being appropriate for patients in lighter weight ranges compared to patients in heavier weight ranges.

[0071] In some embodiments, cabotegravir or a pharmaceutically acceptable salt thereof is provided as a loading dose and one or more maintenance doses, where the loading dose is greater than the one or more maintenance doses. In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is provided as a loading dose and one or more maintenance doses, where the loading dose is greater than the one or more maintenance doses.

[0072] In some embodiments, cabotegravir or a pharmaceutically acceptable salt thereof is provided in a dose of 50 mg to 600 mg, 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 suitable for intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is provided in a dose of 200 mg to 600 mg suitable for intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is provided in a dose of 300 mg to 600 mg suitable for intramuscular injection. In one embodiment, cabotegravir or a pharmaceutically acceptable salt thereof is provided in a dose of 200 mg to 400 mg suitable for intramuscular injection. In some embodiments, cabotegravir or a pharmaceutically acceptable salt thereof is provided as a 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg dose suitable for intramuscular injection.

[0073] In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is provided as a 50 mg to 600 mg dose suitable for intramuscular injection, preferably a 100 mg to 600 mg dose suitable for intramuscular injection, a 150 mg to 600 mg dose suitable for intramuscular injection, a 200 mg to 600 mg dose suitable for intramuscular injection, or a 300 mg to 600 mg dose suitable for intramuscular injection. In one embodiment, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is provided as a 200 mg to 600 mg dose suitable for intramuscular injection. In one embodiment, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is provided as a 300 mg to 600 mg dose suitable for intramuscular injection. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is provided as a 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg dose suitable for intramuscular injection.

[0074] In some embodiments, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are provided as a 50 mg to 600 mg dose suitable for intramuscular injection, preferably a 100 mg to 600 mg dose suitable for intramuscular injection, a 150 mg to 600 mg dose suitable for intramuscular injection, a 200 mg to 600 mg dose suitable for intramuscular injection, or a 200 mg to 400 mg dose suitable for intramuscular injection. In one embodiment, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are provided as a 200 mg to 600 mg dose suitable for intramuscular injection. In one embodiment, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are provided as a 200 mg to 400 mg dose suitable for intramuscular injection. In some embodiments, the one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are provided as 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg doses suitable for intramuscular injection.

[0075] In some embodiments, rilpivirine or a pharmaceutically acceptable salt thereof is provided as a 50 mg to 900 mg dose suitable for intramuscular injection, preferably a 100 mg to 900 mg dose suitable for intramuscular injection, a 150 mg to 900 mg dose suitable for intramuscular injection, a 200 mg to 900 mg dose suitable for intramuscular injection, a 250 mg to 900 mg dose suitable for intramuscular injection, a 300 mg to 900 mg dose suitable for intramuscular injection, a 450 mg to 900 mg dose suitable for intramuscular injection, or a 300 mg to 600 mg dose suitable for 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 provided as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg dose suitable for intramuscular injection.

[0076] In some embodiments, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided as a 50 mg to 900 mg dose suitable for intramuscular injection, preferably a 100 mg to 900 mg dose suitable for intramuscular injection, a 150 mg to 900 mg dose suitable for intramuscular injection, a 200 mg to 900 mg dose suitable for intramuscular injection, a 250 mg to 900 mg dose suitable for intramuscular injection, a 300 mg to 900 mg dose suitable for intramuscular injection, or a 450 mg to 900 mg dose suitable for 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 provided as a 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg dose suitable for intramuscular injection.

[0077] In some embodiments, one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are provided as a 50 mg to 900 mg dose suitable for intramuscular injection, preferably a 100 mg to 900 mg dose suitable for intramuscular injection, a 150 mg to 900 mg dose suitable for intramuscular injection, a 200 mg to 900 mg dose suitable for intramuscular injection, a 250 mg to 900 mg dose suitable for intramuscular injection, a 300 mg to 900 mg dose suitable for intramuscular injection, or a 300 mg to 600 mg dose 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, the one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are provided as 50 mg, 100 mg, 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg doses suitable for intramuscular injection.

[0078] It should be understood that disclosure of amounts (eg, mg) of rilpivirine or a pharmaceutically acceptable salt thereof in injectable form includes the disclosed amount expressed as the base equivalent.

[0079] In some embodiments, the cabotegravir or pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof further comprise an oral induction dose suitable for administration prior to the loading dose. Thus, in some embodiments, the formulated cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof further comprise an induction dose suitable for oral administration prior to the loading dose.

[0080] In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is provided for administration in the form of one or more tablets or one or more dispersible tablets, hi some embodiments, the loading 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.

[0081] In some embodiments, the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are suitable for administration with food.

[0082] In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg to 30 mg acid equivalent, preferably 10 mg to 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 10 mg to 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, or an acid equivalent of 30 mg. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 10 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 30 mg acid equivalent. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a single tablet with an acid equivalent of 30 mg. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is provided for administration as 1, 2, 3, 4, or 5 5 mg acid equivalent dispersible tablets. In some embodiments, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is provided for administration as 2 5 mg acid equivalent dispersible tablets.

[0083] In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg to 25 mg of base equivalent, preferably 12.5 mg to 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 12.5 mg to 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, or 25 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 12.5 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 15 mg of base equivalent. In some embodiments, the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 25 mg of base equivalent. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as one tablet with a base equivalent of 25 mg. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided for administration as 1, 2, 3, 4, 5, 6, 7, or 8 2.5 mg tablets, preferably as tablets dispersed in a liquid. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration as five 2.5 mg tablets, preferably as tablets dispersed in a liquid. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is formulated for administration as six 2.5 mg tablets, preferably as tablets dispersed in a liquid.

[0084] In some embodiments, the cabotegravir or pharmaceutically acceptable salt thereof in the oral formulation is in the form of cabotegravir sodium. In some embodiments, the rilpivirine or 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.

[0085] In some embodiments, an oral bridging dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is provided to a human in place of the scheduled intramuscular injection. Thus, in some embodiments, the use further includes an oral bridging dose, particularly a once-daily oral bridging dose of cabotegravir or a pharmaceutically acceptable salt thereof and / or rilpivirine or a pharmaceutically acceptable salt thereof, in place of the scheduled intramuscular injection, particularly for a human who is at risk of 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 ±7 days after that day. In one embodiment, the final oral bridging dose is provided on, particularly before, the day to resume intramuscular injection.

[0086] In some embodiments, cabotegravir 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 50 or less copies of HIV-1 RNA per mL of plasma. In some embodiments, cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof achieve a viral load of 50 or less copies of HIV-1 RNA per mL of plasma in a human after at least 72 weeks.

[0087] The injectable formulations of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are in the form of long-acting formulations.

[0088] In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is a suspension formulation, particularly a sustained-release suspension for injection or an extended-release suspension for injection. In some embodiments, the concentration of cabotegravir or a pharmaceutically acceptable salt thereof in the suspension is 200 mg / mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 400 mg in a volume of 2 mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof is present in a single-dose vial in an amount of 600 mg in a volume of 3 mL. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises cabotegravir or a pharmaceutically acceptable salt thereof, polysorbate, and polyethylene glycol. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises cabotegravir or a pharmaceutically acceptable salt thereof, mannitol, a polysorbate (e.g., polysorbate 20 or polysorbate 80), polyethylene glycol (PEG) (e.g., PEG3350), and water for injection. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises 200 mg / mL cabotegravir, 35 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG3350, and water for injection. In some embodiments, the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises 200 mg / mL cabotegravir, 45 mg / mL mannitol, 20 mg / mL polysorbate 20, 20 mg / mL PEG3350, and water for injection. In some embodiments, the cabotegravir or a pharmaceutically acceptable salt thereof in the long-acting formulation is in the form of cabotegravir free base.

[0089] In some embodiments, the long-acting formulation of rilpivirine or a pharmaceutically acceptable salt thereof is a suspension formulation, particularly a sustained-release suspension for injection or an extended-release suspension for injection. In some embodiments, the concentration of rilpivirine or a pharmaceutically acceptable salt thereof in the suspension is 300 mg / mL, particularly 300 mg / mL base equivalent. 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 a 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 the 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.

[0090] In some embodiments, the injectable formulation of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the cabotegravir or pharmaceutically acceptable salt thereof is in free form (i.e., non-salt form), and the injectable formulation of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the rilpivirine or pharmaceutically acceptable salt thereof is in free form (i.e., non-salt form). In some embodiments, the injectable formulation of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the cabotegravir or pharmaceutically acceptable salt thereof is in the free acid / base form, and the injectable formulation of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, and the rilpivirine or pharmaceutically acceptable salt thereof is in the free base form.

[0091] Exemplary Dosing Regimen In some embodiments, the human weighs between 35 kg and less than 40 kg, and cabotegravir 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. In some embodiments, the human weighs between 35 kg and less than 40 kg, and a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, and a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 900 mg intramuscular injection. In some embodiments, the human weighs between 35 kg and less than 40 kg, and one or more maintenance doses of cabotegravir 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. 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 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every 2 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 every month ± 7 days or once every 4 weeks ± 7 days, followed by once every 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight weeks ±7 days.In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight 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.

[0092] In some embodiments, an oral induction dose is further administered to a human weighing less than 35 kg to 40 kg. Accordingly, in some embodiments, the method or use further comprises orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalent, and the induction dose of rilpivirine is a once-daily dose of 25 mg base equivalent. In some embodiments, the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least four weeks, particularly once daily for four weeks. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is in the form of cabotegravir sodium. In some embodiments, the induction 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.

[0093] In some embodiments, the human weighs between 25 kg and 34.9 kg, and cabotegravir 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. In some embodiments, the human weighs between 25 kg and 34.9 kg, and a loading dose of cabotegravir 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 600 mg intramuscular injection. In some embodiments, the human weighs between 25 kg and 34.9 kg, and one or more maintenance doses of cabotegravir 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. 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 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every 2 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 every month ± 7 days or once every 4 weeks ± 7 days, followed by once every 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight weeks ±7 days.In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight 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.

[0094] In some embodiments, an oral induction dose is further administered to a human weighing between 25 kg and 34.9 kg. Accordingly, in some embodiments, the method or use further comprises orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent, and the induction dose of rilpivirine is a once-daily dose of 25 mg base equivalent. In some embodiments, the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least four weeks, particularly once daily for four weeks. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two dispersible tablets with an acid equivalent of 5 mg. In some embodiments, the introductory dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a tablet with a base equivalent of 25 mg. In some embodiments, the introductory dose of cabotegravir or a pharmaceutically acceptable salt thereof is in the form of cabotegravir sodium. In some embodiments, the introductory 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.

[0095] In some embodiments, the human weighs between 20 kg and 24.9 kg, and cabotegravir 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. In some embodiments, the human weighs between 20 kg and 24.9 kg, and a loading dose of cabotegravir 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 600 mg intramuscular injection. In some embodiments, the human weighs between 20 kg and 24.9 kg, and one or more maintenance doses of cabotegravir 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. 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 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every 2 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 every month ± 7 days or once every 4 weeks ± 7 days, followed by once every 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight weeks ±7 days.In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight 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.

[0096] In some embodiments, an oral induction dose is further administered to a human weighing between 20 kg and 24.9 kg. Accordingly, in some embodiments, the method or use further comprises orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent, and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalent. In some embodiments, the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least four weeks, particularly once daily for four weeks. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two dispersible tablets with an acid equivalent of 5 mg. In some embodiments, the introductory 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. In some embodiments, the introductory dose of cabotegravir or a pharmaceutically acceptable salt thereof is in the form of cabotegravir sodium. In some embodiments, the introductory 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.

[0097] In some embodiments, the human weighs between 14 kg and 19.9 kg, and cabotegravir 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. In some embodiments, the human weighs between 14 kg and 19.9 kg, and a loading dose of cabotegravir 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. In some embodiments, the human weighs between 14 kg and 19.9 kg, and one or more maintenance doses of cabotegravir 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. 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 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every 2 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 every month ± 7 days or once every 4 weeks ± 7 days, followed by once every 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight weeks ±7 days.In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight 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.

[0098] In some embodiments, an oral induction dose is further administered to a human weighing between 14 kg and 19.9 kg. Accordingly, in some embodiments, the method or use further comprises orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent, and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent. In some embodiments, the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least four weeks, particularly once daily for four weeks. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two dispersible tablets with an acid equivalent of 5 mg. In some embodiments, 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. In some embodiments, the introductory dose of cabotegravir or a pharmaceutically acceptable salt thereof is in the form of cabotegravir sodium. In some embodiments, the introductory 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.

[0099] In some embodiments, the human weighs between 10 kg and 13.9 kg, and cabotegravir 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. In some embodiments, the human weighs between 10 kg and 13.9 kg, and a loading dose of cabotegravir 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. In some embodiments, the human weighs between 10 kg and 13.9 kg, and one or more maintenance doses of cabotegravir 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. 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 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, one or more maintenance doses are administered once every 2 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 every month ± 7 days or once every 4 weeks ± 7 days, followed by once every 2 months ± 7 days or once every 8 weeks ± 7 days. In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight weeks ±7 days.In some embodiments, the one or more maintenance doses are administered once every month ±7 days or once every four 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 eight 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.

[0100] In some embodiments, an oral induction dose is further administered to a human weighing between 10 kg and 13.9 kg. Accordingly, in some embodiments, the method or use further comprises orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent, and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent. In some embodiments, the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered once daily for at least four weeks, particularly once daily for four weeks. In some embodiments, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two dispersible tablets with an acid equivalent of 5 mg. In some embodiments, 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. In some embodiments, the introductory dose of cabotegravir or a pharmaceutically acceptable salt thereof is in the form of cabotegravir sodium. In some embodiments, the introductory 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.

[0101] In some embodiments, the disclosure provides a method of treating HIV infection, the method comprising administering a loading dose comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof, to a human being in need thereof, followed by administering one or more maintenance doses comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof, and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof, wherein the human is between 2 and less than 12 years of age, and a) a human weighing 35 kg to less than 40 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, a 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 cabotegravir 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; or (b) a human (c) a human weighing 25 kg to 34.9 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a 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 cabotegravir 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; or (d) a human weighing 14 kg to 24.9 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a 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 cabotegravir 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; or (d) a human weighing 14 kg to 19.9 kg, and a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, 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 cabotegravir 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) a human body weight of 1 and wherein the patient's weight is between 0 kg and 13.9 kg, a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection, one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection.

[0102] In some embodiments, the human is further administered an oral induction dose. Accordingly, in some embodiments, the method further comprises orally administering induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein (a) if the human weighs between 35 kg and less than 40 kg, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent, or (b) if the human weighs between 25 kg and 34.9 kg, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent, or (c) if the human weighs between 20 kg and 24 kg. (d) if the human body weight is between 14 kg and 19.9 kg, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalent; or (e) if the human body weight is between 10 kg and 13.9 kg, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent.

[0103] In some embodiments, the disclosure provides the use of a loading dose comprising (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof, and one or more maintenance doses comprising (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in treating HIV infection in a human, wherein the human is between 2 and under 12 years of age, and the medicament is formulated for intramuscular injection, and wherein (a) the human (b) a human weighing 35 kg to less than 40 kg, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 900 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are 400 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are 600 mg intramuscular injection, (c) a human weighing 25 kg to 34.9 kg, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a 300 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a 600 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are a 450 mg intramuscular injection, or (d) a human body weight of 14 kg to 19 kg, and the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is 300 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection, and one or more maintenance doses of cabotegravir 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; or9 kg, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a 300 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a 450 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are a 300 mg intramuscular injection, or (e) a human body weight of 1 The present invention provides use of a method for treating a patient with a weight of 0 kg to 13.9 kg, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a 300 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a 450 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are a 300 mg intramuscular injection.

[0104] In some embodiments, the disclosure provides a loading dose comprising (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof, and one or more maintenance doses comprising (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and less than 12 years of age, and the cabotegravir or pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered. is formulated for intramuscular injection, and (a) for a human body weight of 35 kg to less than 40 kg, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is 600 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is 900 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are 400 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are 600 mg intramuscular injection. (b) a human whose body weight is 25 kg to 34.9 kg, and the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a 300 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a 600 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are a 450 mg intramuscular injection, or (c) a human whose body weight is 25 kg to 34.9 kg, and the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a 300 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a 600 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are a 450 mg intramuscular injection, (d) a human weighing 20 kg to 24.9 kg, in which the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a 300 mg intramuscular injection, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a 600 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are a 450 mg intramuscular injection, or9 kg, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is an intramuscular injection of 300 mg, the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is an intramuscular injection of 450 mg, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are an intramuscular injection of 200 mg, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are an intramuscular injection of 300 mg, or (e) the human body weight is 10 kg to 13.9 kg, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is an intramuscular injection of 300 mg, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof is an intramuscular injection of 300 mg. Alternatively, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a 450 mg intramuscular injection, and one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof are a 200 mg intramuscular injection, and one or more maintenance doses of rilpivirine or a pharmaceutically acceptable salt thereof are a 300 mg intramuscular injection.

[0105] In some embodiments, the disclosure provides cabotegravir or a pharmaceutically acceptable salt thereof, in combination with rilpivirine or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and less than 12 years of age, and (a) the human weighs between 35 kg and less than 40 kg, and the cabotegravir or pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection; or (b) the human weighs between 25 kg and 34.9 kg, and the cabotegravir or pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection. (c) when the human body weight is 20 kg to 24.9 kg, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection; (d) when the human body weight is 14 kg to 19.9 kg, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection; or (e) when the human body weight is 10 kg to 13.9 kg, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection.

[0106] In some embodiments, the disclosure provides cabotegravir or a pharmaceutically acceptable salt thereof, in combination with rilpivirine or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and less than 12 years of age, and (a) the human weighs between 35 kg and less than 40 kg, and the cabotegravir or pharmaceutically acceptable salt thereof is formulated as a 400 mg intramuscular injection; or (b) the human weighs between 25 kg and 34.9 kg, and the cabotegravir or pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection. (c) when the human body weight is 20 kg to 24.9 kg, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection; (d) when the human body weight is 14 kg to 19.9 kg, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection; or (e) when the human body weight is 10 kg to 13.9 kg, cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a 200 mg intramuscular injection.

[0107] In some embodiments, the disclosure provides rilpivirine or a pharmaceutically acceptable salt thereof, indicated in combination with cabotegravir or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and less than 12 years of age, and (a) the human weighs between 35 kg and less than 40 kg, and the rilpivirine or pharmaceutically acceptable salt thereof is formulated as a 900 mg intramuscular injection; or (b) the human weighs between 25 kg and 34.9 kg, and the rilpivirine or pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection. (c) when the human body weight is 20 kg to 24.9 kg, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection; (d) when the human body weight is 14 kg to 19.9 kg, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection; or (e) when the human body weight is 10 kg to 13.9 kg, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection.

[0108] In some embodiments, the disclosure provides rilpivirine or a pharmaceutically acceptable salt thereof, indicated in combination with cabotegravir or a pharmaceutically acceptable salt thereof, for use in treating HIV infection in a human, wherein the human is between 2 and less than 12 years of age, and (a) the human weighs between 35 kg and less than 40 kg, and the rilpivirine or pharmaceutically acceptable salt thereof is formulated as a 600 mg intramuscular injection; or (b) the human weighs between 25 kg and 34.9 kg, and the rilpivirine or pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection. (c) when the human body weight is 20 kg to 24.9 kg, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 450 mg intramuscular injection; (d) when the human body weight is 14 kg to 19.9 kg, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection; or (e) when the human body weight is 10 kg to 13.9 kg, rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a 300 mg intramuscular injection.

[0109] In some embodiments, the use further comprises an oral loading dose. Thus, in some embodiments, the use further comprises oral loading doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein (a) for a human body weight of 35 kg to less than 40 kg, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalent, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent, or (b) for a human body weight of 25 kg to 34.9 kg, the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent, or (c) for a human body weight of 20 kg to 24.9 kg. g, the initiation dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the initiation dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalent; (d) if the human body weight is between 14 kg and 19.9 kg, the initiation dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the initiation dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent; or (e) if the human body weight is between 10 kg and 13.9 kg, the initiation dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the initiation dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent.

[0110] Numbered Embodiments Embodiment 1. A method of treating HIV infection, the method comprising: administering to a human being in need thereof a loading dose comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof. wherein the human is between 2 and 12 years of age.

[0111] Embodiment 2. The method of embodiment 1, wherein the human body weight is between 10 kg and less than 40 kg, preferably between 10 kg and 34.9 kg.

[0112] Embodiment 3. The method of embodiment 1 or 2, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is greater than the one or more maintenance doses of cabotegravir or a pharmaceutically acceptable salt thereof.

[0113] 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.

[0114] Embodiment 5. The method of any one of the preceding embodiments, wherein cabotegravir or a pharmaceutically acceptable salt thereof is administered 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.

[0115] 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 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.

[0116] Embodiment 7. The method of any one of the preceding embodiments, wherein one or more maintenance doses are administered at regular intervals.

[0117] Embodiment 8. The method of any one of the preceding embodiments, wherein the one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently.

[0118] Embodiment 9. The method of embodiment 8, wherein one or more maintenance doses are administered once every month ±7 days or once every four weeks ±7 days.

[0119] Embodiment 10. The method of embodiment 9, wherein one or more maintenance doses are administered once every month ±7 days.

[0120] Embodiment 11. The method of embodiment 9, wherein one or more maintenance doses are administered once every 4 weeks ± 7 days.

[0121] Embodiment 12. The method of embodiment 8, wherein one or more maintenance doses are administered once every 2 months ± 7 days or once every 8 weeks ± 7 days.

[0122] Embodiment 13. The method of embodiment 12, wherein one or more maintenance doses are administered once every two months ±7 days.

[0123] Embodiment 14. The method of embodiment 12, wherein one or more maintenance doses are administered every 8 weeks ± 7 days.

[0124] Embodiment 15. The method of embodiment 8, wherein one or more maintenance doses are administered once every 1 month ± 7 days or once every 4 weeks ± 7 days, followed by once every 2 months ± 7 days or once every 8 weeks ± 7 days.

[0125] Embodiment 16. The method of embodiment 15, wherein one or more maintenance doses are administered once every month ±7 days or once every four 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 eight weeks ±7 days.

[0126] Embodiment 17. The method of embodiment 1, wherein the human body weight is less than 35 kg to 40 kg, and wherein cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 400 mg to 600 mg, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 600 mg to 900 mg.

[0127] Embodiment 18. The method of embodiment 17, wherein the loading dose of cabotegravir 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.

[0128] Embodiment 19. The method of embodiment 18, wherein the one or more maintenance doses of cabotegravir 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.

[0129] Embodiment 20. The method of embodiment 1, wherein the human body weight is 25 kg to 34.9 kg, and wherein cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 200 mg to 300 mg, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 450 mg to 600 mg.

[0130] Embodiment 21. The method of embodiment 20, wherein the loading dose of cabotegravir 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.

[0131] Embodiment 22. The method of embodiment 21, wherein the one or more maintenance doses of cabotegravir 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.

[0132] Embodiment 23. The method of embodiment 1, wherein the human body weight is 20 kg to 24.9 kg, and wherein cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 200 mg to 300 mg, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 450 mg to 600 mg.

[0133] Embodiment 24. The method of embodiment 23, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 600 mg.

[0134] Embodiment 25. The method of embodiment 24, wherein the one or more maintenance doses of cabotegravir 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.

[0135] Embodiment 26. The method of embodiment 1, wherein the human body weight is 14 kg to 19.9 kg, and wherein cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 200 mg to 300 mg, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg to 450 mg.

[0136] Embodiment 27. The method of embodiment 26, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 450 mg.

[0137] Embodiment 28. The method of embodiment 27, wherein the one or more maintenance doses of cabotegravir 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.

[0138] Embodiment 29. The method of embodiment 1, wherein the human body weight is 10 kg to 13.9 kg, and wherein cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 200 mg to 300 mg, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg to 450 mg.

[0139] Embodiment 30. The method of embodiment 29, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 300 mg, and the loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as an intramuscular injection of 450 mg.

[0140] Embodiment 31. The method of embodiment 30, wherein the one or more maintenance doses of cabotegravir 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.

[0141] Embodiment 32. The method of any one of embodiments 17-31, wherein one or more maintenance doses are administered once every 4 weeks ± 7 days or less frequently.

[0142] Embodiment 33. The method of embodiment 32, wherein one or more maintenance doses are administered once every month ±7 days or once every four weeks ±7 days.

[0143] Embodiment 34. The method of embodiment 33, wherein one or more maintenance doses are administered once every month ±7 days.

[0144] Embodiment 35. The method of embodiment 33, wherein one or more maintenance doses are administered once every 4 weeks ± 7 days.

[0145] Embodiment 36. The method of embodiment 32, wherein one or more maintenance doses are administered once every 2 months ± 7 days or once every 8 weeks ± 7 days.

[0146] Embodiment 37. The method of embodiment 36, wherein one or more maintenance doses are administered once every 2 months ± 7 days.

[0147] Embodiment 38. The method of embodiment 36, wherein one or more maintenance doses are administered every 8 weeks ± 7 days.

[0148] Embodiment 39. The method of any one of embodiments 19, 22, 25, 28, or 31, wherein one or more maintenance doses are administered once every 1 month ± 7 days or once every 4 weeks ± 7 days, followed by once every 2 months ± 7 days or once every 8 weeks ± 7 days.

[0149] Embodiment 40. The method of embodiment 39, wherein one or more maintenance doses are administered once every month ±7 days or once every four 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 eight weeks ±7 days.

[0150] Embodiment 41. The method of any one of the preceding embodiments, wherein the loading dose of cabotegravir 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.

[0151] Embodiment 42. The method of any one of the preceding embodiments, wherein for each maintenance dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof, the cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered less than 1 hour apart, preferably less than 30 minutes apart.

[0152] Embodiment 43 The method of any one of the preceding embodiments, wherein the intramuscular injection is administered at a site selected from the gluteus medius muscle or the lateral aspect of the thigh.

[0153] Embodiment 44. The method of any one of the preceding embodiments, wherein the injectable cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof is in the form of a long-acting formulation.

[0154] Embodiment 45. The method of embodiment 44, wherein the long-acting formulation of cabotegravir or a pharmaceutically acceptable salt thereof comprises cabotegravir or a pharmaceutically acceptable salt thereof, polysorbate, and polyethylene glycol.

[0155] 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.

[0156] Embodiment 47. The method of any one of the preceding embodiments, further comprising orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose.

[0157] Embodiment 48. The method of embodiment 47, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg to 30 mg acid equivalent, preferably a daily dose of 10 mg to 30 mg acid equivalent.

[0158] Embodiment 49. The method of embodiment 48, wherein the induction 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.

[0159] Embodiment 50. The method of any one of embodiments 17-19, further comprising orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalent and the induction dose of rilpivirine is a once-daily dose of 25 mg base equivalent.

[0160] Embodiment 51. The method of embodiment 50, wherein the induction dose of cabotegravir 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.

[0161] Embodiment 52 The method of embodiment 50 or 51, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0162] Embodiment 53. The method of embodiment 52, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0163] Embodiment 54. The method of any one of embodiments 20-22, further comprising orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine is a once-daily dose of 25 mg base equivalent.

[0164] Embodiment 55. The method of embodiment 54, wherein the induction dose of cabotegravir 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.

[0165] Embodiment 56. The method of embodiment 54 or 55, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0166] Embodiment 57. The method of any one of embodiments 54-56, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0167] Embodiment 58. The method of embodiment 57, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0168] Embodiment 59. The method of any one of embodiments 23-25, further comprising orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalent.

[0169] Embodiment 60. The method of embodiment 59, wherein the induction dose of cabotegravir 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.

[0170] Embodiment 61. The method of embodiment 59 or 60, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0171] Embodiment 62. The method of any one of embodiments 59-61, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as six 2.5 mg base equivalent tablets, preferably dispersed in a liquid.

[0172] Embodiment 63 The method of any one of embodiments 59-62, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0173] Embodiment 64. The method of embodiment 63, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0174] Embodiment 65. The method of any one of embodiments 26-28, further comprising orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent.

[0175] Embodiment 66. The method of embodiment 65, wherein the induction dose of cabotegravir 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.

[0176] Embodiment 67. The method of embodiment 65 or 66, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0177] Embodiment 68. The method of any one of embodiments 65 to 67, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as five 2.5 mg base equivalent tablets, preferably dispersed in a liquid.

[0178] Embodiment 69. The method of any one of embodiments 65-68, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0179] Embodiment 70. The method of embodiment 69, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0180] Embodiment 71. The method of any one of embodiments 29-31, further comprising orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent.

[0181] Embodiment 72. The method of embodiment 71, wherein the induction dose of cabotegravir 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.

[0182] Embodiment 73. The method of embodiment 71 or 72, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as two 5 mg acid equivalent dispersible tablets.

[0183] Embodiment 74. The method of any one of embodiments 71 to 73, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as five 2.5 mg base equivalent tablets, preferably dispersed in a liquid.

[0184] Embodiment 75. The method of any one of embodiments 71-74, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine.

[0185] Embodiment 76. The method of embodiment 75, wherein the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

[0186] Embodiment 77. The method of any one of embodiments 47 to 76, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more dispersible tablets.

[0187] Embodiment 78. The method of any one of embodiments 47 to 77, wherein the induction 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.

[0188] Embodiment 79. The method of any one of embodiments 47-78, wherein the induction doses of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are administered with food.

[0189] Embodiment 80 The method of any one of the preceding embodiments, wherein the human exhibits a viral load of 50 copies of HIV-1 RNA per mL of plasma or less prior to initiation of treatment.

[0190] Embodiment 81 The method of any one of the preceding embodiments, wherein the human exhibits a viral load of HIV-1 RNA of 50 copies per mL of plasma or less after at least 72 weeks of treatment.

[0191] Embodiment 82. A method of treating HIV infection, comprising: administering to a human being in need thereof a loading dose comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof; thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof. The human is between 2 and 12 years old, (a) In a human weighing 35 kg to less than 40 kg, a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 600 mg intramuscular injection, a 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 cabotegravir 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; or (b) a human weighing 25 kg to 34.9 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a 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 cabotegravir 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; or (c) a human weighing 20 kg to 24.9 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a 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 cabotegravir 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; or (d) a human weighing between 14 kg and 19.9 kg, wherein a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, 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 cabotegravir 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 method, wherein the human body weight is 10 kg to 13.9 kg, a loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered as a 300 mg intramuscular injection, a loading dose of rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 450 mg intramuscular injection, one or more maintenance doses of cabotegravir 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.

[0192] Embodiment 83. The method further comprises orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose; (a) for a human weighing 35 kg to less than 40 kg, the infusion dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 30 mg acid equivalent and the infusion dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent; or (b) for a human weighing 25 kg to 34.9 kg, the infusion dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the infusion dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 25 mg base equivalent; or (c) for a human weighing 20 kg to 24.9 kg, the infusion dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the infusion dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 15 mg base equivalent; or (d) for a human weighing between 14 kg and 19.9 kg, the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent; or (e) The method of embodiment 82, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a once-daily dose of 10 mg acid equivalent and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a once-daily dose of 12.5 mg base equivalent for a human weighing between 10 kg and 13.9 kg.

[0193] Embodiment 84. Use of (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in treating HIV infection in a human, wherein the human is between 2 and less than 12 years of age, and the medicament is formulated for regular intramuscular injection.

[0194] Embodiment 85. Cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine, or a pharmaceutically acceptable salt thereof, for use in the treatment of HIV infection in a human, wherein the human is 2 to less than 12 years of age, and the cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine, or a pharmaceutically acceptable salt thereof, are formulated for regular intramuscular injection.

[0195] Embodiment 86. Cabotegravir or a pharmaceutically acceptable salt thereof, indicated in combination with rilpivirine or a pharmaceutically acceptable salt thereof, for use in the treatment of HIV infection in a human, wherein the human is 2 to less than 12 years of age, and the cabotegravir or pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection.

[0196] Embodiment 87. Rilpivirine or a pharmaceutically acceptable salt thereof, indicated in combination with cabotegravir or a pharmaceutically acceptable salt thereof, for use in the treatment of HIV infection in a human, wherein the human is 2 to less than 12 years of age, and the rilpivirine or pharmaceutically acceptable salt thereof is formulated for regular intramuscular injection.

[0197] It is understood that any and all embodiments of the present disclosure may be taken in combination with any one or more other embodiments to describe additional more preferred embodiments. Also, each individual element of a preferred embodiment should be understood to be its own independent preferred embodiment. Furthermore, any element of an embodiment is intended to be combined with any and all other elements of any embodiment to describe additional embodiments. [Example]

[0198] [Example 1] Phase I / II trial of CAB LA and RPV LA in children research design This phase I / II, multicenter, open-label, non-comparative study will evaluate the safety, tolerability, acceptability, and PK of long-acting injectable CAB (CAB LA) and long-acting injectable RPV (RPV LA) across weight-range dosing regimens following oral CAB and oral RPV in HIV-1-infected, virologically suppressed children aged 2 to 12 years. The study will also evaluate long-acting injectable regimens with and without an oral lead-in period in the same study population. CAB LA will be formulated as a suspension containing 200 mg / mL cabotegravir free acid for administration by IM injection. RPV LA will be formulated as a suspension containing 300 mg / mL RPV free base for administration by IM injection.

[0199] The study will be conducted in up to 90 children weighing 10 kg to less than 40 kg who are virologically suppressed on stable ART. Approximately 90 parents / guardians of the 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 noted, the term "participants" refers to children enrolled in the study.

[0200] The study included two cohorts.

[0201] In Cohort 1, participants will be enrolled in five weight bands: weight band 1 (35-<40 kg), weight band 2 (25-34.9 kg), weight band 3 (20-24.9 kg), weight band 4 (14-19.9 kg), and weight band 5 (10-13.9 kg).

[0202] Once enrolled in Cohort 1, participants in each weight range proceed through two study participation steps. During Step 1 (i.e., at study entry), participants switch from their pre-study ART regimen to a daily oral formulation of CAB and oral formulation of RPV for at least 4 weeks and up to 6 weeks. Participants who meet the eligibility criteria based on the Week 4a visit move on to Step 2 and receive injectable CAB LA + injectable RPV LA until Week 72. Participants who prematurely and permanently discontinue oral CAB + RPV or do not meet the eligibility criteria for the injectable phase exit the study 28 days after their last oral study medication dose. During Step 2, participants receive injectable CAB LA + RPV LA. Two IM injections of CAB LA single injection and RPV LA single injection will be administered at the Week 4b (Step 2 entry) visit, the Week 8 visit, and then continued every 4 weeks or every 8 weeks thereafter, depending on the recommendation of the interim analysis at Week 12, with the final injection administered at the Week 72 visit. In both steps, participants will follow the dosing regimen outlined in the Product Regimen section below.

[0203] Cohort 2 consists of two groups, Cohort 2a and Cohort 2b, and participants can choose a regimen with or without oral induction. Participants enrolled in Cohort 2a will progress through two steps of study participation as described for Cohort 1. Cohort 2a participants will receive oral CAB plus oral RPV (Step 1) until the Week 4b visit, followed by intramuscular CAB LA and parenteral RPV LA from Week 4b (Step 2 entry) through Week 48, based on the currently recommended relevant weight-range dosing regimen. Participants enrolled in Cohort 2b will skip the oral induction phase and will receive both CAB LA and RPV LA at study entry, based on the currently recommended relevant weight-range dosing regimen, and continue through Week 44.

[0204] The decision to participate in Cohort 2a or Cohort 2b is made by the potential study participant and / or parent / legal guardian in consultation with the investigator or designee and, if applicable, other healthcare providers. This choice must be made as part of the informed consent or assent process and confirmed prior to study entry. Participants cannot change their choice of Cohort 2a or Cohort 2b group after enrollment.

[0205] Product Regimen At entry, all participants will discontinue their pre-study cART regimen and will be assigned to a dosing regimen based on their weight at entry into the applicable cohort. Weight-based dose adjustments will be made according to the guidelines provided in the Dose Adjustments section below. Dosing regimens may be modified after the interim analysis of Cohort 1 or based on experience in the study, in which case the new regimen will be identified according to the Dosing Regimen Modifications section below.

[0206] Participants in Cohort 1 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).

[0207] 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 intramuscular CAB LA and intramuscular RPV LA only.

[0208] [Table 1]

[0209] [Table 2]

[0210] Based on modeling and analysis of previous data, initial doses have been determined for each weight range, and oral and long-acting regimens using the suggested initial doses in Tables 1 and 2 have been calculated to achieve plasma concentrations within the acceptable range of those clinically observed in adolescents and adults.

[0211] Dose adjustment A participant's weight at the entry visit will establish the participant's weight range and assigned oral medication for the duration of the oral lead-in phase. No adjustments to oral medication will be made due to changes in weight range (weight gain or loss) that may occur during the oral lead-in phase.

[0212] At each injection visit, participants' weight will be assessed prior to administration of study medication to determine the appropriate weight range and injection dosing regimen to be administered at that visit. Participants with increasing weight ranges will begin the dosing regimen corresponding to their new applicable weight range; however, doses will not be changed if weight ranges decrease. Participants will remain on the dosing regimen for the maximum weight range achieved.

[0213] Modification of medication regimen Modifications to the weight-range dosing regimen may be made as needed after the interim analysis of Cohort 1 and / or based on ongoing review of safety, PK, viral load, tolerability, and all other relevant data within this study or from other ongoing studies of the investigational drug in the pediatric population. Dose modifications, and the initial dose for Cohort 2 above, will be selected from Tables 3-8. Currently enrolled and newly enrolled participants will be assigned to the most recent dosing regimen.

[0214] If the injection regimen is amended from Q4W to Q8W dosing, enrolled participants still in the oral run-in phase will be able to receive injections on a Q8W schedule. Enrolled participants who start on a Q4W injection schedule and complete 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.

[0215] Regardless of dosing regimen modifications, each dosing regimen will include, where applicable, the daily oral doses of cabotegravir 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.

[0216] [Table 3]

[0217] [Table 4]

[0218] [Table 5]

[0219] [Table 6]

[0220] [Table 7]

[0221] [Table 8]

[0222] [Table 9]

[0223] Oral bridging in participants receiving LA injections Optionally, participants who miss a scheduled injection may receive daily oral CAB+RPV as a bridging strategy. The weight-range dosing regimen of oral investigational drug will be assigned according to the participant's weight obtained at the most recent study visit (whether a regularly scheduled visit or an interim visit).

[0224] Participants will ideally begin the oral bridging regimen on the same target visit date (or within the same target visit period) as the missed injection visit. The last dose of the short-term oral bridging regimen should occur on the same day as and before the resumption of injectable study medication. Participants in Step 2 may require an interim injection visit when resuming study medication injections to properly resume their dosing regimen or to readjust to their original injection visit dosing schedule.

Claims

1. 1. A method of treating an HIV infection, said method comprising: administering a loading dose comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof to a human being in need thereof; thereafter administering one or more maintenance doses comprising (i) an intramuscular injection of cabotegravir or a pharmaceutically acceptable salt thereof and (ii) an intramuscular injection of rilpivirine or a pharmaceutically acceptable salt thereof. wherein the human is between 2 and under 12 years of age.

2. 2. The method according to claim 1, wherein the human body weight is between 10 kg and less than 40 kg, preferably between 10 kg and 34.9 kg.

3. Cabotegravir or a pharmaceutically acceptable salt thereof is administered 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, and rilpivirine or a pharmaceutically acceptable salt thereof is administered as a 50 mg to 600 mg intramuscular injection.

3. The method of claim 1 or 2, wherein the compound is administered as an intramuscular injection of 100 mg to 900 mg, preferably as an intramuscular injection of 150 mg to 900 mg, 200 mg to 900 mg, 250 mg to 900 mg, 300 mg to 900 mg, 450 mg to 900 mg, or 300 mg to 600 mg.

4. 4. The method of any one of claims 1 to 3, 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 claims 1 to 4, wherein the injectable solutions of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof are in the form of a long-acting formulation.

6. 6. The method of any one of claims 1 to 5, wherein the injectable solution of cabotegravir or a pharmaceutically acceptable salt thereof is formulated as a suspension, wherein the cabotegravir or a pharmaceutically acceptable salt thereof is in the form of the free acid / base, and the injectable solution of rilpivirine or a pharmaceutically acceptable salt thereof is formulated as a suspension, wherein the rilpivirine or a pharmaceutically acceptable salt thereof is in the form of the free base.

7. 7. The method of any one of claims 1 to 6, further comprising orally administering an induction dose of cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof prior to the loading dose.

8. 8. The method of claim 7, wherein the induction dose of cabotegravir or a pharmaceutically acceptable salt thereof is a daily dose of 5 mg to 30 mg acid equivalent, preferably 10 mg to 30 mg acid equivalent, and the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is a daily dose of 2.5 mg to 25 mg base equivalent, preferably 12.5 mg to 25 mg base equivalent.

9. 9. The method of claim 7 or 8, wherein the loading dose of cabotegravir or a pharmaceutically acceptable salt thereof is administered in the form of one or more tablets or one or more dispersible tablets, and the loading 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. 10. The method according to any one of claims 7 to 9, wherein the induction dose of rilpivirine or a pharmaceutically acceptable salt thereof is provided by a pharmaceutically acceptable salt of rilpivirine, preferably the pharmaceutically acceptable salt of rilpivirine is rilpivirine hydrochloride.

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

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

13. 1. Use of (i) cabotegravir or a pharmaceutically acceptable salt thereof and (ii) rilpivirine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in treating HIV infection in a human, wherein the human is between the ages of 2 and less than 12 years, and the medicament is formulated for regular intramuscular injection.

14. 1. Cabotegravir or a pharmaceutically acceptable salt thereof and rilpivirine, or a pharmaceutically acceptable salt thereof, for use in the treatment of HIV infection in a human, wherein the human is 2 to less than 12 years of age, and the cabotegravir or pharmaceutically acceptable salt thereof and rilpivirine, or a pharmaceutically acceptable salt thereof, are formulated for regular intramuscular injection.

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

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

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