Pharmaceutical compositions

Abstract

The present invention relates to Human Immunodeficiency Virus (HIV) prevention and treatment. In particular, the invention relates to a pharmaceutical composition comprising a prodrug of cabotegravir and a poloxamer.

Description

[0001] PHARMACEUTICAL COMPOSITIONS FIELD OF THE INVENTION The invention relates to treatment or prevention of Human Immunodeficiency Virus (HIV) infection. In particular, the invention relates to long-acting treatment or prevention ofHIV infection.BACKGROUND TO THE INVENTION Patients with HIV infection commonly undergo complex treatment regimens which involve taking multiple pills at regular intervals each day. Patient non-compliance is a known problem accompanying these complex HIV treatment regimens and can lead to the emergence of multiple drug resistant strains of HIV. The application of long-acting parenteral pharmaceuticals has been established in clinical practice for decades, notably in the areas of contraception, anti-psychotics, and opiate addiction. More recently, long-acting parenteral pharmaceuticals have been proposed as a way of overcoming the non-compliance problem with HIV treatment regimens. Long-acting injectable formulations, some of which are approved and marketed, such as CABENUVA®, have demonstrated prolonged exposures (≥ 30 days) following injection, enabling dosing at once-monthly and bimonthly intervals. WO 2017 / 223280 and WO 2020 / 086555 disclose integrase inhibitor prodrugs, specifically prodrugs of cabotegravir. These prodrugs may have an extended drug half-life and therefore allow for less frequent dosing compared to the parent compound which could help alleviate issues with patient non-compliance. Achieving an injectable suspension of anti-HIV drug in order to dose less frequently and overcome the non-compliance problem with HIV treatment regimens, whilst keeping the same or similar injection volume as previous HIV treatment regimens in order to maintain patient experience, is desirable. Similarly, where an anti-HIV drug may be used for prevention of HIV infection (e.g., pre-exposure prophylaxis, or PrEP), achieving aninjectable suspension with an anti-HIV drug that provides a longer-acting effect couldincrease adherence due to less frequent dosing. Suspensions may suffer from difficulty inresuspension and particle size growth. Moreover, suspensions with larger particle sizes (e.g., on micron scale) are more difficult to stabilize in ready-to-use suspensions. Lyophilized formulations for micro-suspensions offer several advantages overready-to-use suspensions – namely, avoiding reconstitution / resuspension difficulties orfailures, maintaining product physicochemical stability, and overcoming scale-up issues. It is expected that drug substance polymorphism could impact pharmacokinetics(PK) and or bioavailability of suspensions, due to potential solubility difference of different solid-state forms. Identification of a stable, crystalline form of a compound with suitable properties for long-acting administration and a pharmaceutical composition that arrests formconversion would be highly desirable for the treatment and prevention of HIV infection.There is a need in the art for a long-acting injectable to treat or prevent HIV infection that can be dosed at longer intervals whilst still achieving the same patient experience,minimizing injection-site reactions, and overcoming known difficulties with polymorphic formconversion, particle size and high concentration suspensions. SUMMARY OF THE INVENTION According to a first aspect, there is provided a pharmaceutical compositioncomprising Compound A, (Compound A), and a According to a second aspect, there is provided a method of treating humanimmunodeficiency virus (HIV) infection in a human in need thereof comprising administering to said human a therapeutically effective amount of the pharmaceutical composition as described herein. According to a third aspect, there is provided a method of preventing humanimmunodeficiency virus (HIV) infection in a human in need thereof comprising administering to said human an effective amount of the pharmaceutical composition as described herein. According to a further aspect, there is provided a pharmaceutical composition asdescribed herein, for use in therapy. According to a still further aspect, there is provided a pharmaceutical composition asdescribed herein for use in treatment or prevention of human immunodeficiency virus (HIV)infection. According to a still further aspect, there is provided, use of a pharmaceutical compositionas described herein, in the manufacture of a medicament for treatment of humanimmunodeficiency virus (HIV) infection.In a still further aspect, there is provided a kit comprising a container comprising thepharmaceutical composition as described herein as a lyophilised powder.The pharmaceutical compositions of the present invention may be advantageous in anumber of respects. The pharmaceutical compositions of the invention favourably reduce Cmaxand extend half-life compared to existing formulations, thus permitting ultra long-actingtherapy, allowing for longer time intervals between dosing compared to existing therapies.This may improve patient compliance, reducing likelihood of drug-resistant HIV strains. Compositions of the invention have also been shown to show particle size stability overtime, even at a range of different temperature conditions allowing for favourable product storage. Compositions of the present invention also favourably prevent form conversion overtime, specifically, Form 1 (the most thermodynamically stable single component form ofCompound A) has been shown to remain stable in the pharmaceutical composition duringstorage, i.e. does not convert to another form over time, as well as remaining stable whenexposed to conditions of varying temperature and humidity.  It is expected that drugsubstance polymorphism could impact pharmacokinetics / bioavailability of drug product, dueto potential solubility difference of different solid-state forms. Presence of otherpolymorphic forms or groups in drug product and conversion of drug substance to otherforms or groups during drug product processing highlight the risks of conversion to anunintended form during manufacturing and lack of control of the levels of less stable drug substance form in drug product resulting in variable mixtures of forms in the drug productand potentially variable bioavailability of the drug product. Compositions of the inventionlimit polymorphic form conversion of Form 1 of Compound A in the composition and offerenhanced control over solid state form, with form conversion less than 10%. BRIEF DESCRIPTION OF THE DRAWINGS Fig.1 shows an X-ray powder diffraction pattern of Form 1 of Compound A measured at room temperature with Cu Ka1radiation at 1.54 Angstroms. Fig. 2 shows a differential scanning calorimetry thermogram of Form 1 of Compound A.Collected at room temperature up to 160 deg C at a heating rate of 10 deg C / min using asealed hermetic aluminium pan with a pinhole. Fig. 3 shows a thermogravimetric analysis trace of Form 1 of Compound A. Collected atroom temperature up to 400 deg C at a heating rate of 15 deg C / min in an open aluminiumpan.Fig. 4 shows a Raman spectrum of Form 1 of Compound A. Raman spectra was collectedusing a Kaiser Optical Systems Raman RXN2-785 controlled by iCRaman software v4.4.21. Resampling Intervals were: 1 cm-1; Channel 2. A RXN Probe + Hastelloy C276 ImmersionOptic Laser with a Wavelength of 785nm (short focus, 6mm dia, 203mm long) was used.Parameters are as follows: Laser Power set at 400mW, detector Temperature -40°C, cosmic Ray Removal ON, Peak Intensity Correction ON, 1s Acquisition Time. Fig.5 shows an X-ray powder diffraction pattern of form, Group B of Compound A.Fig. 6 shows X-ray powder diffraction pattern of multicomponent form, Group E ofCompound A.Fig. 7 shows a comparison of X-ray powder diffraction patterns for a micronized andlyophilized composition of Compound A. Fig. 8 shows an XRPD of Form 1 made from a method without using a seeding step according to Example 1. Fig.9 shows a DSC of Form 1 made from a method without using a seeding step according to Example 1. Fig.10 shows an XRPD of Form 1 made from the method of Example 2b.Fig. 11 shows a 19F solid-state Nuclear Magnetic Resonance (NMR) spectrum of Form 1 ofCompound A.Fig. 12 shows a log plot of the Cabotegravir plasma concentrations time course aftersubcutaneous administration in Cynomolgus monkeys (A) Sodium Carboxymethylcellulose formulation at 40 mg / Kg (○) and 75 mg / Kg (☐) of compound A (B) of PolyvinylpyrrolidoneK12 formulation at 40 mg / Kg (∆) and 75 mg / Kg (x) of compound A.Fig. 13 shows a high resolution X-ray powder diffraction pattern (XRPD) of Form 1 ofCompound A measured at room temperature with Cu Ka1radiation at 1.54 Angstroms.Fig. 14 shows a DSC of Group B (made using impurities from the drug substance processand Form 1). Fig.15 shows an overlay of XRPDs of several mixtures of Group B and Form 1 (Top to bottom(50:50, 70:30, 90:10, 95:5 Form 1: Grp B)), second from the bottom pure Group B, bottompure Form 1. Fig. 16 shows an overlay of XRPDs of several mixtures of Group B and Form 1 (Top to bottom (50:50, 70:30, 90:10, 95:5 Form 1: Grp B)), second from the bottom pure GroupB, bottom pure Form 1 in the range of 4.5 to 9.5 °2θ.Fig. 17 shows an overlay of XRPDs of several mixtures of Group B and Form 1 (Top to bottom (50:50, 70:30, 90:10, 95:5 Form 1: Grp B)), second from the bottom pure GroupB, bottom pure Form 1 in the range of 19.0 to 24.5 °2θ. DETAILED DESCRIPTION OF THE INVENTION DEFINITIONS As used herein, the term “alkyl” refers to a saturated hydrocarbon radical, straight or branched, having the specified number of carbon atoms. For example, the term “C1-6 alkyl” refers to an alkyl group having 1 to 6 carbon atoms. Exemplary groups include, but are not limited to, methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, sec-butyl, isobutyl and tert-butyl), pentyl, and hexyl. As used herein, the term "aqueous solution" refers to any solution comprising water or in which the solvent is water. Additionally, "aqueous solution" is used to describe solutions displaying commonalities to water or watery solutions, not limited to characteristics such as appearance, smell, color, taste, viscosity, pH, absorbance, or physical state under particular temperatures. The term “treatment” refers to ameliorating or stabilising the specified condition, reducing or eliminating the symptoms of the condition, slowing or eliminating the progression of the condition, and preventing or delaying reoccurrence of the condition in a previously afflicted patient or subject. As used herein, the term “prevention” refers to avoidance of the stated disease in a subject who is not suffering from the stated disease. As used herein, the term “therapeutically effective amount” refers to the quantityof a compound of formula (I) [and insert any others], or a pharmaceutically acceptable salt thereof, which will elicit the desired biological response in a human body. It may vary depending on the compound, the disease and its severity and the age and weight of the subject to be treated. As used herein, the term “lyophilization,” also known as freeze-drying or cryodesiccation, is a dehydration process which involves freezing the product without destroying the physical structure of the matter. As used herein, the terms "lyophilized" and "freeze-dried" can be used interchangeably herein and refer to a condition and / or state of a sample, formulation, or product obtained by means of lyophilization. As used interchangeably herein, the terms “lyophilized pharmaceuticalcomposition” and “lyophilized composition” refer to a pharmaceutical composition inlyophilized form, as taught herein. As used herein, the term “pharmaceutical composition” means a composition that is suitable for pharmaceutical use. As used herein, "reconstitution" refers to the process of restoring a dried, lyophilized, dehydrated, or concentrated matter to its original or liquid state by adding a solvent to the lyophilized matter, allowing the lyophilized matter to rehydrate, followed by agitating the mixture of the solvent and lyophilized matter. The reconstituted matter may be part of a product, formulation, sample, raw material, or any biological material but is certainly not limited to matter falling under the common definition of these terms. Reconstitution can be assessed visually with the naked eye. The lyophilized matter is deemed reconstitutedwhen a homogeneous suspension is observed. In particular, a suspension with a cloudyappearance is considered suitably reconstituted. As used herein, the term “self-administered” means administration by someone other than a healthcare professional, for example, a patient may administer the pharmaceutical composition to their self or someone else, other than a healthcare professional administering the pharmaceutical composition to the patient. As used herein, the term “subject” or “patient” refers to a human. As used herein, the term “size” refers to a spherical volume equivalent size. As used herein, X50 (or “the X50 value”) is the particle size, in microns, at which50% by volume of the particles have a smaller size and 50% by volume have a larger size,also known as the mass median size (MMS) or the median of the particle size distributionby volume. As used herein, X90 (or “the X90 value”) is the particle size, in microns, at which90% by volume of the particles have a smaller size and 10% by volume have a larger size.As used herein, X10 (or “the X10 value”) is the particle size, in microns, at which10% by volume of the particles have a smaller size and 90% by volume have a larger size.DESCRIPTION OF THE EMBODIMENTS In a first aspect, there is provided a pharmaceutical composition comprisingCompound A A) Compound A (3R,6S)-12-{[(2,4-difluorophenyl)methyl]carbamoyl}-6-methyl-8,11-dioxo-4- oxa-1,7-diazatricyclo[7.4.0.0³,⁷]trideca-9,12-dien-10-yl octadecenoate is a stearoyl ester prodrug of cabotegravir. Other ester prodrugs of cabotegravir are disclosed in WO 2017 / 223280 and WO2020 / 086555 and are incorporated by reference herein. In an embodiment of the invention, the ester prodrug of cabotegravir may be a compound of Formula I: (Formula I) R C3-C30In an embodiment R is an alkyl chain of length 3 to 30 carbons. In an embodimentR is C10-C20alkyl. In an embodiment R is C15-C20alkyl. In an embodiment R is C15-C18alkyl.In any of the mentioned embodiments, the alkyl chain may be a linear alkyl chain i.e. R isthe residue of a fatty acid. In an embodiment R is a linear 17 carbon alkyl i.e. the esterprodrug of cabotegravir is Compound A. Cabotegravir (3S,11AR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7- dioxo-2,3,5,7,11,11a-hexahydrooxazolo [3,2-a] pyrido[1,2-d]pyrazine-8-carboxamide is described in US 8,129,385 in example Z-1, which example is incorporated herein by reference. Cabotegravir is an integrase strand transfer inhibitor (INSTI) that exhibits subnanomolar potency and antiviral activity against a broad range of HIV-1 strains. Oral administration of cabotegravir has exhibited acceptable safety and tolerability profiles, a long half-life, and few drug-drug interactions. Cabotegravir has been demonstrated to be efficacious in treatment and prevention of HIV infection both in oral and parenteral dosage forms, see for instance, Margolis DA, Brinson CC, Eron JJ, et al.744 and Rilpivirine as Two Drug Oral Maintenance Therapy: LAI116482 (LATTE) Week 48 Results. 21stConference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2014; Boston, MA, Margolis DA, Podzamczer D, Stellbrink H-J, et al. Cabotegravir + Rilpivirine as Long-Acting Maintenance Therapy: LATTE-2 Week 48 Results, 21stInternational AIDS Conference; July 18-22, 2016; Durban, South Africa, Abstract THAB0206LB. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2016, and Markowitz M, Frank I, Grant R, et al. ÉCLAIR: Phase 2A Safety and PK Study of Cabotegravir LA in HIV- Uninfected Men. Abstract presented at 23rdCROI; February 22-25, 2016; Boston, MA. Cabotegravir has been approved by the FDA for long-acting prevention of HIV infection dosed every two months; and in combination with Rilpivirine for long-acting treatment of HIV infection dosed once a month or once every two months. Cabotegravir is represented by Compound B: (Compound B). a (also referred to herein as the steric acid ester prodrug of cabotegravir) which is less soluble than cabotegravir thus providing opportunity for longer dosing intervals. In an embodiment, the pharmaceutical compositions of the present inventioncomprise particles of crystalline Compound A. In an embodiment, Compound A particles of the pharmaceutical composition havea mass median size (X50) value greater than or equal to 1 μm and less than or equal to 15μm (i.e., 1 μm ≤ X50 ≤ 15 μm). Particle size distribution may be measured by any suitablemethod, for example, by laser diffraction as described in the Examples section herein. In an embodiment, Compound A is present in the composition as Form 1 i.e. themost thermodynamically stable single component form of Compound A. Form 1 is asdescribed herein. In an embodiment, Compound A is present at a concentration of 100 to 600 mg / mL.In a further embodiment, the pharmaceutical composition contains about 200 mg / mLto about 400 mg / mL of Compound A. In a further embodiment, the composition contains,about 200 mg / mL, about 300 mg / mL, or about 400 mg / mL of Compound A.In another embodiment, the pharmaceutical composition contains Compound A inan amount between about 600 mg to about 1800 mg. Wetting agents or surfactants are compounds that, when dissolved in a liquid, can reduce the surface tension of a gas, liquid, or solid surface in that liquid. They are often amphiphilic and may aid in wetting and enhance manufacturability of the drug product. In addition, a surfactant may additionally impart long-term product stability by steric or electrostatic repulsion. Non-ionic surfactants are preferred over ionic surfactants as theyare generally non-toxic, non-irritating, and inert. Examples of surfactants which could beused in the pharmaceutical composition include, but are not limited to, polysorbate 20(Tween-20), polysorbate 80 (Tween-80), sorbitan monolaurate (Span-20), sorbitan monooleate (Span-80), poloxamer 188 (Kolliphor P188), poloxamer 338 (Kolliphor P338), and poloxamer 407 (Kolliphor P407). Pharmaceutical compositions of the invention comprise a poloxamer as a wettingagent. Poloxamers are nonionic triblock copolymers composed of a central hydrophobicchain of polyoxypropylene (polypropylene oxide) flanked by two hydrophilic chains ofpolyoxyethylene (polyethylene glycol). Poloxamers are represented by Formula II. Poloxamers are also known by the trade names Synperonics, Pluronics, and Kolliphor. Poloxamers are commonly named with the letter "P" followed by three digits, the first two digits x 100 give the approximate molecular mass of the polyoxypropylene core, and the last digit x 10 gives the percentage polyoxyethylene content (e.g., P407 = Poloxamer with a polyoxypropylene molecular mass of 4,000 g / mol and a 70% polyoxyethylene content). In an embodiment of the present invention, the poloxamer may be P188, P338 orP407. P188, P338 and P407 are commercially available. In an embodiment of the invention,the poloxamer is P338. Without wishing to be bound by theory, it is thought that poloxamer may play a role in limiting form conversion in the pharmaceutical composition. Further, the present inventors have found that using a poloxamer in the pharmaceutical composition of thepresent invention lowers viscosity of the pharmaceutical composition compared to othersurfactants or wetting agents. In an embodiment, the pharmaceutical composition contains from about 5 mg / mL toabout 15 mg / mL of the poloxamer. In a further embodiment, the pharmaceutical compositioncontains from about 10mg / mL to about 15 mg / mL of the poloxamer.In an embodiment the pharmaceutical composition contains from about 1 to 5 % w / vof the poloxamer. In an embodiment, the pharmaceutical composition contains about 1 to2% w / v of the poloxamer. In an embodiment, a weight ratio of the poloxamer to Compound A is in a range of from 1:10 to 1:50. In another embodiment, the weight ratio of the poloxamer to Compound A is in a range of from 1:10 to 1:40. In another embodiment, the weight ratio of the poloxamer to Compound A is in a range of from 1:25 to 1:35. In another embodiment, the weight ratio of the poloxamer to Compound A is about 1:30. In an embodiment, the pharmaceutical composition further comprises a stabilizer and a tonicity adjuster. Stabilizers are components added to help preserve critical product attributes throughout shelf life. In the case of suspensions, stabilizers can be used to induce charge effects, add steric stabilization, increase viscosity of the vehicle, etc. These factors can preserve particle size, product resuspendability, and / or improve manufacturability. Examples of stabilizers include, but are not limited to, sodium carboxymethylcellulose (CMC), polyethylene glycol 3350, polyethylene glycol 4000, and polyvinylpyrrolidone (PVP) (e.g., povidone K12 (PVP K12) and povidone K17 (PVP K17)). In an embodiment, the pharmaceutical composition of the invention comprisessodium CMC (NaCMC) or polyvinylpyrrolidone (PVP) as the stabilizer. In an embodiment,the pharmaceutical composition of the invention comprises sodium CMC as the stabilizer. In another embodiment, the pharmaceutical composition of the invention comprises polyvinylpyrrolidone (PVP) as the stabiliser. In an embodiment the PVP is PVP K12. The present inventors have found that PVP and NaCMC, in comparison to other stabilisers (forexample polyethylene glycol (PEG)), lower viscosity of the composition allowing for effectivereconstitution / resuspension. The present inventors have also found that PVP, incomparison to NaCMC, lowers viscosity of the composition allowing for effectivereconstitution / resuspension. In an embodiment, the pharmaceutical composition contains about 1 mg / mL to about30 mg / mL of the stabilizer. In a further embodiment, the pharmaceutical compositioncontains about 1 mg / mL to about 25 mg / mL, from about 2 mg / mL to about 15 mg / mL, or from about 5 mg / mL to about 15 mg / mL of the stabilizer. In an embodiment, thepharmaceutical composition contains about 5 mg / mL of the stabilizer. In an embodiment,the pharmaceutical composition contains about 10 mg / mL of the stabilizer. In anembodiment, the pharmaceutical composition contains about 15 mg / mL of the stabilizer. Inan embodiment, the pharmaceutical composition contains about 20 mg / mL of the stabilizer.In an embodiment the pharmaceutical composition contains from about 0.1 to 5 %w / v of the stabilizer. In an embodiment, the pharmaceutical composition contains about 0.1to 2% w / v of the stabilizer. In an embodiment, the stabilizer is NaCMC and the pharmaceutical composition comprises about 0.5 % w / v of NaCMC. In another embodiment, the stabilizer is PVP and the pharmaceutical composition comprises about 1.5 % w / v of PVP. In another embodiment, the stabilizer is PVP K12 and the pharmaceutical composition comprises about 1.5 % w / v of PVP K12. In an embodiment, a weight ratio of the stabilizer to Compound A is in a range of from 1:5 to 1:100. In another embodiment, the weight ratio of the stabilizer to Compound A is in a range of from 1:10 to 1:80. In an embodiment, the stabiliser is PVP and the weight ratio of the stabilizer to Compound A is in a range of 1:5 to 1:40. In another embodiment, the stabiliser is PVP and the weight ratio of the stabilizer to Compound A is in a range of 1:10 to 1:30. In an embodiment, the stabiliser is PVP and the weight ratio of the stabilizer to Compound A isabout 1:15 to 1:25. In an embodiment, the stabiliser is PVP and the weight ratio of thestabilizer to Compound A is about 1:20. In an embodiment, the stabiliser is PVP K12 and the weight ratio of the stabilizer to Compound A is in a range of 1:5 to 1:40. In another embodiment, the stabiliser is PVP K12 and the weight ratio of the stabilizer to Compound A is in a range of 1:10 to 1:30. In another embodiment, the stabiliser is PVP K12 and the weight ratio of the stabilizer to Compound Ais in a range of 1:15 to 1:25. In an embodiment, the stabiliser is PVP K12 and the weightratio of the stabilizer to Compound A is about 1:20. In an embodiment, the stabiliser is NaCMC and the weight ratio of the stabilizer toCompound A is in a range of 1:40 to 1:80. In another embodiment, the stabiliser is NaCMCand the weight ratio of the stabilizer to Compound A is in a range of 1:50 to 1:70. In anembodiment, the stabiliser is NaCMC and the weight ratio of the stabilizer to Compound Ais about 1:60. Tonicity adjusters act to provide and maintain a stable tonicity for the pharmaceuticalcomposition disclosed herein. In some embodiments, tonicity adjusters also function as a non-aqueous solvent, a solubilizer, and / or a stabilizer. In such instances, tonicity adjusters may be used at concentrations higher than needed for tonicity if their primary purpose is stabilization or may be used at concentrations higher than needed for stabilization if their primary purpose is tonicity adjustment. In some embodiments, the tonicity adjuster is a pharmaceutically acceptableinorganic chloride, e.g., potassium chloride, sodium chloride, magnesium chloride orcalcium chloride. In yet other embodiments, the tonicity adjuster is a saccharide such asmannitol, sorbitol, lactose, trehalose, raffinose, dextrose, maltose, galactose, sucrose, orpolysucrose. In still further aspects, the tonicity adjuster is mannitol. In other aspects, thetonicity adjuster is a non-aqueous polar aprotic or protic materials such as polyethyleneglycol, N,N-dimethylacetamide, N-methyl pyrrolidone, glycerol, propylene glycol, ethanol, t- butyl alcohol, benzyl alcohol, benzyl benzoate, dimethyl sulfoxide, or glycerol. In furtheraspects, the tonicity adjuster is a polymer such as polyethylene glycol (PEG) (for example,PEG 300, PEG 400, PEG 3350, PEG 6000, or PEG 8000), polygalacturonic acid,galacturonic acid, or polyvinylpyrrolidine (PVP). In still other aspects, the tonicity adjuster isan amino acid such as lysine, arginine, glycine, methionine, or other amino acids. In yetfurther aspects, the tonicity adjuster is a cyclodextrin such as dextran, Ficoll, orpolyvinylpyrrolidone, or other similar excipients and combinations of these agents. In an embodiment, the pharmaceutical composition of the invention comprises mannitol as the tonicity adjuster. In an embodiment, the pharmaceutical composition contains about 0.1 mg / mL toabout 250 mg / mL of the tonicity adjuster. In a further embodiment, the pharmaceuticalcomposition contains about 10 mg / mL to about 50 mg / mL, from about 25 mg / mL to about50 mg / mL, from about 30 mg / mL to about 45 mg / mL of the tonicity adjuster. In anembodiment, the pharmaceutical composition contains about 35 mg / mL of the tonicity adjuster. In an embodiment the pharmaceutical composition contains from about 0.1 to 5 %w / v of the tonicity adjuster. In an embodiment, the pharmaceutical composition containsabout 2 to 4 % w / v of the tonicity adjuster. In an embodiment, the pharmaceutical composition contains about 3.5 % w / v of the tonicity adjuster. In an embodiment, a weight ratio of the tonicity adjuster to cabotegravir is in a range of from 1:5 to 1:50. In another embodiment, the weight ratio of the tonicity adjuster toCompound A is in a range of from 1:5 to 1:35. In another embodiment, the weight ratio ofthe tonicity adjuster to cabotegravir is in a range of from 1:5 to 1:25. In another embodiment, the weight ratio of the tonicity adjuster to cabotegravir is in a range of from 1:5 to 1:10. In another embodiment, the weight ratio of the tonicity adjuster to cabotegravir is in a range of from 1:5 to 1:12. In another embodiment, the weight ratio of the tonicity adjuster to cabotegravir is about 1:9. In another embodiment, the weight ratio of the tonicity adjuster to cabotegravir is about 1:8.5. Dissolution properties of the pharmaceutical composition are affected, inter alia, by particle size and particle size distribution of the active pharmaceutical ingredient (i.e., Compound A). In an embodiment, the pharmaceutical composition has a particle size distributionby volume such that 50% of the Compound A particles have a particle size less than orequal to 10 μm (i.e. mass median size, or X50, is 10 μm). In an embodiment, Compound Aparticles have an X50 value greater than or equal to 3 μm and less than or equal to 8.5 μm (i.e., 3 μm ≤ X50 ≤ 8.5 μm). In an embodiment, Compound A particles have a mass mediansize (X50) of between (and including) 3 μm and 6 μm. In an embodiment, Compound Aparticles have a mass median size (X50) of between (and including) 3 μm and 5 μm.In an embodiment, the pharmaceutical composition has a mass median size (X50)of 3.0 μm, 3.1 μm, 3.2 μm, 3.3 μm, 3.4 μm, 3.5 μm, 3.6 μm, 3.7 μm, 3.8 μm, 3.9 μm, 4.0μm, 4.1 μm, 4.2 μm, 4.3 μm, 4.4 μm, 4.5 μm, 4.6 μm, 4.7 μm, 4.8 μm, 4.9 μm or 5.0 μm. Inan embodiment, the pharmaceutical composition has a mass median size (X50) of about 3μm. In an embodiment, the pharmaceutical composition has a mass median size (X50) ofabout 4 μm. In an embodiment, the pharmaceutical composition has a mass median size (X50) of about 5 μm. In an embodiment, the pharmaceutical composition has a particle size distributionby volume such that 90% of the Compound A particles have a particle size less than orequal to 25 μm (i.e., X90 is 25 μm). In an embodiment, Compound A particles of the pharmaceutical composition have an X90 value greater than or equal to 5 μm and less than or equal to 25 μm (i.e., 5 μm ≤ X90 ≤ 25 μm), provided that X90 is larger than X50. In an embodiment, the pharmaceutical composition has a particle size distribution by volume suchthat 90% of the Compound A particles have a particle size less than or equal to 20 μm (i.e.,X90 is 20 μm). In an embodiment, Compound A particles of the pharmaceutical compositionhave an X90 value greater than or equal to 8 μm and less than or equal to 13 μm (i.e., 8 μm≤ X90 ≤ 13 μm).In an embodiment, the pharmaceutical composition has a particle size distributionby volume such that 90% of the Compound A particles (X90) have a particle size smallerthan or equal to 7.0 μm, 7.1 μm, 7.2 μm, 7.3 μm, 7.4 μm, 7.5 μm, 7.6 μm, 7.7 μm, 7.8 μm, 7.9 μm, 8.0 μm, 8.1 μm, 8.2 μm, 8.3 μm, 8.4 μm, 8.5 μm, 8.6 μm, 8.7 μm, 8.8 μm, 8.9 μm,9.0 μm, 9.1 μm, 9.2 μm, 9.3 μm, 9.4 μm, 9.5 μm, 9.6 μm, 9.7 μm, 9.8 μm, 9.9 μm, 10.0 μm,10.1 μm, 10.2 μm, 10.3 μm, 10.4 μm, 10.5 μm, 10.6 μm, 10.7 μm, 10.8 μm, 10.9 μm, 11.0 μm, 11.1 μm, 11.2 μm, 11.3 μm, 11.4 μm, 11.5 μm, 11.6 μm, 11.7 μm, 11.8 μm, 11.9 μm, 12.0 μm, 12.1 μm, 12.2 μm, 12.3 μm, 12.4 μm, 12.5 μm, 12.6 μm, 12.7 μm, 12.8 μm, 12.9 μm, 13.0 μm, 13.1 μm, 13.2 μm, 13.3 μm, 13.4 μm, 13.5 μm, 13.6 μm, 13.7 μm, 13.8 μm,13.9 μm or 14.0 μm. In another embodiment, the pharmaceutical composition has a particlesize distribution by volume such that 90% of the Compound A particles (X90) have a particlesize smaller than or equal to 9 μm (i.e., X90 is 9 μm). In another embodiment, thepharmaceutical composition has a particle size distribution by volume such that 90% of theCompound A particles (X90) have a particle size smaller than or equal to 9.5 μm (i.e., X90is 9.5 μm). In another embodiment, the pharmaceutical composition has a particle sizedistribution by volume such that 90% of the Compound A particles (X90) have a particlesize smaller than or equal to 11 μm (i.e., X90 is 11 μm).In an embodiment, the pharmaceutical composition has a particle size distributionby volume such that 10% of the Compound A particles have a particle size smaller than orequal to 4 μm (i.e., X10 is 4 μm). In an embodiment, Compound A particles of thepharmaceutical composition have an X10 value greater than or equal to 0.5 μm and less than or equal to 4 μm (i.e., 0.5 μm ≤ X10 ≤ 4 μm). In an embodiment, the pharmaceutical composition has a particle size distribution by volume such that 10% of the Compound Aparticles have a particle size less than or equal to 3.5 μm. In an embodiment, CompoundA particles of the pharmaceutical composition have an X10 value greater than or equal to 1μm and less than or equal to 3.5 μm (i.e., 1 μm ≤ X10 ≤ 3.5 μm). In an embodiment, the pharmaceutical composition has a particle size distribution by volume such that 10% of theCompound A particles have a particle size less than or equal to 3 μm. In an embodiment,Compound A particles of the pharmaceutical composition have an X10 value greater thanor equal to 1.5 μm and less than or equal to 3 μm (i.e., 1.5 μm ≤ X10 ≤ 3 μm). In an embodiment, the pharmaceutical composition has a particle size distributionby volume such that 10% of the Compound A particles (X10) have a particle size smallerthan or equal to 1.0 μm, 1.1 μm, 1.2 μm, 1.3 μm, 1.4 μm, 1.5 μm, 1.6 μm, 1.7 μm, 1.8 μm, 1.9 μm, 2.0 μm, 2.1 μm, 2.2 μm, 2.3 μm, 2.4 μm, 2.5 μm, 2.6 μm, 2.7 μm, 2.8 μm, 2.9 μm, 3.0 μm, 3.1 μm, 3.2 μm, 3.3 μm, 3.4 μm, 3.5 μm, 3.6 μm, 3.7 μm, 3.8 μm, 3.9 μm, or 4.0 μm. In another embodiment, the pharmaceutical composition has a particle size distributionby volume such that 10% of the Compound A particles (X10) have a particle size smallerthan or equal to 1.7 μm (i.e., X10 is 1.7 μm). In another embodiment, the pharmaceutical composition has a particle size distribution by volume such that 10% of the Compound Aparticles (X10) have a particle size smaller than or equal to 2.2 μm (i.e., X10 is 2.2 μm).The value X90 refers to the 90% value of the volume distribution measured using a laser diffractometer. For purposes of the present disclosure, the X90 value denotes the particle size below which 90% of the quantity of particles is found based on the volume distribution. Analogously, the value X50 refers to the 50% value (median) of the volume distribution measured using a laser diffractometer. For purposes of the present disclosure, the X50 value denotes the particle size below which 50% of the quantity of particles is found based on the volume distribution. Analogously, the value X10 refers to the 10% value of the volume distribution measured using a laser diffractometer. For purposes of the present disclosure, the X10 value denotes the particle size below which 10% of the quantity of particles is found based on the volume distribution. In an embodiment, all X90, X50, and X10 values described herein are by volume and determined by laser diffraction method. The laser diffraction method is sensitive to the volume of a particle and provides a volume-average particle size, which is equivalent to the weight-average particle size if the density is constant. It will be apparent to those skilled in the art that the results of the particle size distribution determination by one technique can be correlated with that from another technique, for example on an empirical basis by routine experimentation. Alternatively, particle size distribution can be determined by microscopy, in particular electron microscopy or scanning electron microscopy. The inventors have found that lyophilized pharmaceutical compositions ofCompound A with particle size sizes in the microns achieve an extended long-acting profile compared to other formulations, for example compositions of smaller particle sizes and which are not lyophilized. Lyophilized compositions of the invention have been shown tohave lower Cmax and longer half-life as shown, for example, in Example 5 herein. Further,the inventors have found that lyophilized compositions, compared to, for example, compositions that have been wet bead milled, limit form conversion from Form 1 of Compound A. Lyophilization comprises at least a freezing step and a sublimation step. Lyophilization may be used in the manufacturing of pharmaceutical products and intermediates thereof. During freezing, the material is cooled to a temperature wherein thesolid, liquid, and gas phases of the material may exist. Active pharmaceutical productingredients (APIs) may be lyophilized to achieve chemical and physical stability allowingroom temperature storage. This is different from a conventional method that evaporateswater using heat. Advantages of lyophilization may include, but are not limited to, enhancedstability of a dry powder, the removal of water without excessive heating of the product, and enhanced product stability in a dry state. In an exemplary method of preparing a lyophilized formulation of the invention,micronized Compound A is packaged in antistatic linear low-density polyethylene bags. Thepackaged Compound A is enclosed in a corrugated plastic box and gamma irradiated as a bioburden reduction step and referred to as gamma irradiated Compound A. Gamma irradiated Compound A is dispersed in a filtered aqueous vehicle comprising a stabilizer (e.g., PVP or sodium CMC), a tonicity agent (e.g., mannitol), and a wetting agent (e.g.,Poloxamer e.g. Poloxamer 338). The resulting suspension is homogenized, filled intowashed, sterilized / depyrogenated 10 mL Type I clear glass vials. Container materials are then processed: vials are depyrogenated by dry heat, and stoppers and overseals are sterilized by steam. Product vials are lyophilized, backflushed with nitrogen, sealed with halobutyl rubber stoppers and secured by an aluminum overseal. The sealed vials are terminally sterilized by gamma irradiation. As evidenced in the examples, which illustrate certain representative embodiments of the invention, the inventors have developed lyophilized pharmaceutical compositions and methods to obtain said compositions that allow for larger-size particles of Compound A. Data provided herein indicate that such lyophilized pharmaceutical compositions contribute to improved pharmacokinetic properties, thus addressing one or more above-mentioned problems in the art. In an embodiment, the lyophilized pharmaceutical composition is a suspension. The lyophilized pharmaceutical composition advantageously suspends when reconstituted in an aqueous or non-aqueous solution, that is, all or substantially all, such as at least 90 percent, at least 95 percent, at least 96 percent, at least 97 percent, at least 98 percent, at least 99 percent, at least 99.5 percent or 100 percent of the lyophilized pharmaceuticalcomposition is suspended when reconstituted.Reconstitution can be assessed visually with the naked eye. The lyophilized matteris deemed reconstituted when a homogeneous suspension is observed. In particular, asuspension with a cloudy appearance is considered suitably reconstituted. It will be apparent to those skilled in the art that pharmaceutical compositions of the invention may be reconstituted in an aqueous or non-aqueous solution to a desired concentration. For example, the pharmaceutical composition described below in Example3 may be reconstituted in 1.1 mL water for injection (WFI) to achieve a Compound Aconcentration of 400 mg / mL. Similarly, the same pharmaceutical composition describedbelow in Example 2 may be reconstituted in 1.7 mL WFI to achieve a Compound Aconcentration of 300 mg / mL.In an embodiment, the present disclosure provides a lyophilized pharmaceuticalcomposition comprising Compound A, wherein Compound A is present in the form ofparticles having a mass median size (X50) of between (and including) 1.5 μm and 15 μm;a poloxamer; a stabilizer; and a tonicity adjuster; wherein the formulation, when reconstituted in an aqueous solution, has a reconstitution time of 15 minutes or less, 10 minutes or less, or 5 minutes or less. In another embodiment, the present disclosure provides a lyophilizedpharmaceutical composition comprising Compound A, wherein Compound A is present inthe form of particles having a mass median size (X50) of between (and including) 1.5 μmand 15 μm; poloxamer; sodium CMC; and mannitol; wherein the formulation, whenreconstituted in an aqueous or non-aqueous solution, has a reconstitution time of 15 minutes or less, 10 minutes or less, or 5 minutes or less. In another embodiment, the present disclosure provides a lyophilized pharmaceutical composition comprising Compound A, wherein Compound A is present inthe form of particles having a mass median size (X50) of between (and including) 1.5 μmand 15 μm; poloxamer; PVP; and mannitol; wherein the formulation, when reconstituted in an aqueous or non-aqueous solution, has a reconstitution time of 15 minutes or less, 10 minutes or less, or 5 minutes or less. In an embodiment, Compound A is present in the pharmaceutical composition as crystalline Form 1 of Compound A. Pharmaceutical compositions of the present invention surprisingly prevent form conversion of Form 1 to other forms. Form landscape studies for Compound A identified Form 1 as the most thermodynamically stable single component polymorphic form in the solid state. The drugsubstance has been shown to convert to Group B (shown in Fig. 5), and multicomponentGroup E (shown in Fig. 6) of Compound A which can form through multiple avenuesincluding in the presence of formulation excipients (for example, if polysorbates are usedinstead of poloxamers) as well as aliphatic impurities. Development work conducted using wet bead milling process resulted in in-situ formconversion of drug substance from stable single component Form 1 to a Group B, withestimated form conversion of approximately 90% conversion if uncontrolled. Selection of: (i) poloxamers in comparison to other wetting agents, for examplepolysorbates; (ii) drug substance particle size; and (iii) lyophilization, which due to resultantsolid cake prevents further form change risk during shelf life of the product in comparison to a nano-suspension dosage form wherein significantly higher form conversion happensduring manufacturing and on shelf life, have all been found to be important in arresting formconversion of Compound A. The pharmaceutical compositions disclosed herein limit polymorphic formconversion of the drug substance in the formulation and therefore offer enhanced control over solid state form in the drug product, with form conversion estimated to be less than 10%.   Polymorphic form In an embodiment, Compound A is present in the pharmaceutical composition as Form 1 of Compound A. Form 1 is a crystalline form of Compound A. Specifically, Form 1 is the mostthermodynamic single component form of Compound A.In an embodiment, crystalline Form 1 of Compound A is characterised by an X-ray powder diffraction (XRPD) pattern substantially in accordance with Figure 1. An XRPD pattern will be understood to comprise a diffraction angle (expressed indegrees 2 ) of “about” a value specified herein when the XRPD pattern comprises adiffraction angle within 0.3 degrees 2 of the specified value. Further, it is well known andunderstood to those skilled in the art that the apparatus employed, humidity, temperature, orientation of the powder crystals, and other parameters involved in obtaining an XRPDpattern may cause some variability in the appearance, intensities, and positions of the linesin the diffraction pattern. An XRPD pattern that is “substantially in accordance” with that ofFigure 1 provided herein is an XRPD pattern that would be considered by one skilled in the art to represent a compound possessing the same crystal form as the compound that provided the XRPD pattern of Figure 1. That is, the XRPD pattern may be identical to that of Figure 1 or more likely it may be somewhat different. Such an XRPD pattern may not necessarily show each of the lines of the diffraction pattern presented herein, and / or may show a slight change in appearance, intensity, or a shift in position of said lines resulting from differences in the conditions involved in obtaining the data. A person skilled in the art is capable of determining if a sample of a crystalline compound has the same form as, or adifferent form from, the form disclosed herein by comparison of their XRPD patterns. Forexample, one skilled in the art can overlay an XRPD pattern of a sample of a different form or group of Compound A, with Figure 1 and, using expertise and knowledge in the art, readily determine whether the XRPD pattern of the sample is substantially in accordance with the XRPD pattern of Form 1 of Compound A. If the XRPD pattern is substantially in accordance with Figure 1, the sample form can be readily and accurately identified as being Form 1 of Compound A. In an embodiment Form 1 is characterised by an XRPD pattern exhibiting at leastX-ray peaks (2-theta values) in a powder diffractogram when measured using Cu Kα1radiation at 1.54 Angstroms. In an embodiment, Form 1 is characterised by an XRPD pattern exhibiting reflections at 2θ angles when measured using Cu Kα radiation at 1.54 Angstroms. As discussed above, a XRPD pattern of Form 1 is shown in Fig.1. The corresponding reflections and heights are provided in Table 1 below. Table 1 Pos. [°2θ] Height [counts]3.4 121053.26.8 4443.27.4 5438.511.2 1148.615.5 2035.316.7 6175.816.9 5587.917.5 7519.117.9 5006.618.2 6936.618.7 7237.519.2 2033.420.2 1847.620.7 2638.821.1 2489.521.4 3073.721.9 3286.522.2 6338.123.5 3730.324.0 1806.325.7 2332.127.2 1541.131.8 570.934.2 442.3In an embodiment, Form 1 is characterised by an XRPD pattern exhibiting reflections at 2θ angles when measured using Cu Kα radiation at 1.54 Angstroms. An XRPD pattern of Form 1 is shown in Fig.13. The corresponding reflections and relative intensity heights are provided in Table 1a below. In an embodiment, crystalline Form 1 of Compound A is characterised by an X-ray powder diffraction (XRPD) pattern substantially in accordancewith Fig. 13.Table 1a Pos.[°2θ] Rel. Int. [%]3.3698 1006.7315 2.737.4005 6.4710.1169 0.4711.1797 0.8714.4579 0.1114.822 0.4214.8982 0.3915.4631 0.3516.6326 2.2116.8147 2.4217.4803 5.4717.8264 6.4818.1517 4.118.6537 5.118.8051 1.4319.1282 1.0920.1335 1.120.3043 0.8320.6023 1.6620.9643 1.8121.2623 1.8221.861 1.6522.1256 2.7922.3169 0.422.4952 1.5322.7597 0.2523.2415 2.423.4309 2.7123.6784 0.74 24.0015 1.624.4777 0.8124.7979 1.1625.1382 0.0725.5726 1.6626.0349 0.126.6782 0.1626.9399 0.3827.0625 1.2127.6868 0.1428.0767 0.2428.4944 -0.0628.8843 0.1429.263 0.1129.3605 0.3329.5415 0.0629.7838 0.2530.1221 0.2530.292 -0.0230.8211 0.1630.9659 0.2731.6704 0.1332.1522 0.0332.5263 0.1132.6656 0.0933.5456 0.1434.8225 0.0435.2597 035.6607 0.0936.5713 0.1137.6017 0.0537.7743 0.0538.0055 0.0538.3199 0.0339.1469 0.0939.47 0.0739.729 0.1139.9768 0.0140.5883 0.03 In an embodiment, Form 1 is characterised by an XRPD pattern exhibiting reflections at2θ angles of about 6.8, 7.4, 16.7, 16.9, 17.5, 17.9, 18.2, 18.7, 21.9, and 22.2o, whenmeasured using Cu Kα radiation at 1.54 Angstroms. In one embodiment, Form 1 ischaracterised by an XRPD pattern exhibiting reflections at 2θ angles of about 6.8, 7.4, 16.7,16.9, 17.5, 17.9, 18.2, and 18.7 o, when measured using Cu Kα radiation at 1.54 Angstroms.In one embodiment, Form 1 is characterised by an XRPD pattern exhibiting reflections at a 2θ angle at about 7.4oand at least 2, at least 3, or at least 4 of the 2θ angles selected fromabout 6.8, 16.7, 16.9, 17.5, 17.9, 18.2, 18.7, 21.9, and 22.2 o, when measured using Cu Kαradiation at 1.54 Angstroms. The absence of peaks between about 6.75 and 7.25 °2θ and at about 21.6 °2θ mayindicate that undetectable amounts of Group B of Compound A, discussed herein are present. In an embodiment Form 1 is characterised by a19F solid-state NMR (SSNMR) spectrum substantially in accordance with Fig.11. It is well known and understood to those skilled in the art that the apparatus employed, humidity, temperature, orientation of the powder crystals, and other parameters involved in obtaining an NMR spectrum may cause some variability in the appearance, intensities, and positions of the peaks in the spectrum. An NMR spectrum that is“substantially in accordance” with that of Fig. 11 provided herein is an NMR spectrum thatwould be considered by one skilled in the art to represent Form 1 of Compound A. That is,the NMR spectrum may be identical to that of Fig. 11 or more likely it may be somewhatdifferent. Such an NMR spectrum may not necessarily show each of the peaks of any one of the spectra presented herein, and / or may show a slight change in appearance, intensity, or a shift in position of said peaks resulting from differences in the conditions involved in obtaining the data. A person skilled in the art is capable of determining if a sample of a crystalline compound has the same form as, or a different form from, the form disclosed herein by comparison of their NMR spectra. For example, one skilled in the art can overlaya Raman spectrum of a different form or group of Compound A with Fig. 11 and, usingexpertise and knowledge in the art, readily determine whether the NMR spectrum of the sample is substantially in accordance with the NMR spectrum of Form 1 of Compound A. If the NMR spectrum is substantially in accordance with Fig. 11, the sample form can be readily and accurately identified as having Form 1 of Compound A. In an embodiment, Form 1 is characterised by a differential scanning calorimetry (DSC)spectrum substantially in accordance with Figure 2. In an embodiment, the DSC thermogram of Form 1 of Compound A exhibits a single endotherm with an onset temperature of about 121 °C. In an embodiment, Form 1 of Compound A is characterized by a DSC spectrum with a single endotherm with an onset temperature of about 121oC. Ina further embodiment, Form 1 of Compound A is characterized by a DSC trace substantiallyin accordance with Figure 2 and / or a thermogravimetric analysis trace substantially inaccordance with Figure 3. In an embodiment, the DSC thermogram of Form 1 of CompoundA exhibits a single endotherm, with an onset temperature of about 121 °C. In an embodiment, the DSC thermogram of Form 1 of Compound A exhibits a single endotherm, with an onset temperature of 121 °C. In an embodiment, the DSC thermogram of Form 1 of Compound A does not exhibit a broad peak at about 40 to about 80 °C. In an embodiment, the DSC thermogram of Form 1 of Compound A does not exhibit a broad peak at 40 to 80 °C. In an embodiment, Form 1 is characterized by a Raman spectrum substantially in accordance with Fig 4. Raman spectra was collected using a Kaiser Optical Systems Raman RXN2-785 controlled by iCRaman software v4.4.21. Resampling Intervals were: 1 cm-1; Channel 2. A RXN Probe + Hastelloy C276 Immersion Optic Laser with a Wavelength of 785nm (short focus, 6mm dia, 203mm long) was used. Parameters are as follows: Laser Power set at 400mW, detector Temperature -40°C, cosmic Ray Removal ON, Peak Intensity Correction ON, 1s Acquisition Time. A Raman spectrum will be understood to comprise a peak (expressed in cm-1) of “about” a value specified herein when the Raman spectrum comprises a peak within 5.0 cm-1of the specified value. Further, it is also well known and understood to those skilled in the art that the apparatus employed, humidity, temperature, orientation of the powder crystals, and other parameters involved in obtaining a Raman spectrum may cause some variability in the appearance, intensities, and positions of the peaks in the spectrum. ARaman spectrum that is “substantially in accordance” with that of Fig. 4 provided herein isa Raman spectrum that would be considered by one skilled in the art to represent a compound possessing the same crystal form as the compound that provided the Ramanspectrum of Fig. 4 i.e. Form 1 of Compound A. That is, the Raman spectrum may beidentical to that of Fig. 4 or more likely it may be somewhat different. Such a Ramanspectrum may not necessarily show each of the peaks of any one of the spectra presented herein, and / or may show a slight change in appearance, intensity, or a shift in position of said peaks resulting from differences in the conditions involved in obtaining the data. A person skilled in the art is capable of determining if a sample of a crystalline compound has the same form as, or a different form from, a form disclosed herein by comparison of their Raman spectra. In an embodiment, Compound A is characterized by a Raman spectrum comprising at least 3 peaks at positions selected from a group consisting of peaks at 1820 to 1720 cm-1, 670 to 570cm cm-1, and 270 to 200 cm-1. In still further embodiments, as a person having ordinary skill in the art will understand, Form 1 of Compound A is characterized by any combination of the analytical data characterizing the aforementioned embodiments. For example, in one embodiment, Form 1 of Compound A is characterized by an XRPD pattern substantially in accordancewith Fig. 1 and a DSC trace substantially in accordance with Fig.2 and a thermogravimetricanalysis trace substantially in accordance with Fig.3 and a Raman trace substantially inaccordance with Fig.4 and an 19F SSNMR substantially in accordance with Fig. 11. In oneembodiment, Form 1 of Compound A is characterized by an XRPD pattern substantially inaccordance with Fig. 13 and a DSC spectrum substantially in accordance with Fig 2.In another embodiment, Form 1 of Compound A is characterized by an X-raypowder diffraction (XRPD) pattern substantially in accordance with Fig. 1 and a DSC tracesubstantially in accordance with Fig.2. In another embodiment, Form 1 of Compound A is characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with Fig.1 and a thermogravimetric analysis trace substantially in accordance with Fig.3. In an embodiment, Form 1 of Compound A is characterized by an XRPD pattern exhibiting reflections at 2θ angles of about 7.4owhen measured using Cu Kα radiation at 1.54 Angstroms and a DSC spectrum with a single endotherm with an onset temperature of about 121oC. Solid forms of Compound A disclosed in the art are believed to be mixtures of multicomponent forms. Specifically, the XRPD pattern of such solid forms show high amounts of multicomponent Group B (shown in Fig.5 and described in Example 1). Having mixtures of groups or forms could impact pharmacokinetics and / or bioavailability of suspensions, due to potential solubility difference of different solid-state forms. In an embodiment, the pharmaceutical composition comprises Form 1 in at least 90% polymorphic purity. In an embodiment, Form 1 of Compound A is in at least 90% polymorphic purity. In an embodiment, Form 1 of Compound A is in at least 95% polymorphic purity. In an embodiment, Form 1 of Compound A is in at least 99% polymorphic purity . Exemplary embodiments In an embodiment, the pharmaceutical composition comprises Compound A,poloxamer P338 and NaCMC. In another embodiment, the pharmaceutical composition comprises Compound A, poloxamer P338 and PVP. In another embodiment, the pharmaceutical composition comprises Compound A, poloxamer P338 and PVP K12. In an embodiment, the pharmaceutical composition comprises Compound A,poloxamer P338, NaCMC, and mannitol; and Compound A is present in the form of particleshaving a mass median size (X50) of between (and including) 1.5 μm and 15 μm. In thisembodiment the pharmaceutical composition may comprise Compound A in an amount of30 % w / v, mannitol in an amount of 3.5 % w / v, poloxamer P338 in an amount of 1 % w / v,and NaCMC in an amount of 0.5 % w / v. In another embodiment, the pharmaceutical composition comprises Compound A,poloxamer P338, PVP, and mannitol; and Compound A is present in the form of particleshaving a mass median size (X50) of between (and including) 1.5 μm and 15 μm. In thisembodiment the pharmaceutical formulation may comprise Compound A in an amount of30 % w / v, mannitol in an amount of 3.5% w / v, poloxamer P338 in an amount of 1% w / v, and PVP in an amount of 1.5 % w / v. In another embodiment, the pharmaceutical composition comprises Compound A,poloxamer P338, PVP K12, and mannitol; and Compound A is present in the form ofparticles having a mass median size (X50) of between (and including) 1.5 μm and 15 μm.In this embodiment the pharmaceutical formulation may comprise Compound A in an amount of 30 % w / v, mannitol in an amount of 3.5% w / v, P338 in an amount of 1% w / v, and PVP K12 in an amount of 1.5 % w / v. In an embodiment, the pharmaceutical composition comprises Compound A,poloxamer P338, NaCMC, and mannitol; and Compound A is present in the form of particleshaving a mass median size (X50) of between (and including) 1.5 μm and 15 μm. In thisembodiment mannitol is present at a weight ratio of mannitol to Compound A of about 1:8.5; P338 is present at a weight ratio of P338 to Compound A of about 1:30; and NaCMC is present at a weight ratio of NaCMC to Compound A of about 1:60. In another embodiment, the pharmaceutical composition comprises Compound A,poloxamer P338, PVP, and mannitol; and Compound A is present in the form of particleshaving a mass median size (X50) of between (and including) 1.5 μm and 15 μm. In thisembodiment mannitol is present at a weight ratio of mannitol to Compound A of about 1:8.5; poloxamer P338 is present at a weight ratio of P338 to Compound A of about 1:30; and PVP is present at a weight ratio of PVP to Compound A of about 1:20. In another embodiment, the pharmaceutical composition comprises Compound A, poloxamer P338, PVP K12, and mannitol; and Compound A is present in the form ofparticles having a mass median size (X50) of between (and including) 1.5 μm and 15 μm.In this embodiment mannitol is present at a weight ratio of mannitol to Compound A of about 1:8.5; P338 is present at a weight ratio of P338 to Compound A of about 1:30; and PVP K12 is present at a weight ratio of PVP to Compound A of about 1:20. In another embodiment, the pharmaceutical composition comprises Compound A, poloxamer P338, PVP, and mannitol; and Compound A is present in the form of particleshaving a mass median size (X50) of between (and including) 2 μm and 5 μm. In anotherembodiment, the pharmaceutical composition comprises Compound A, poloxamer P338, PVP, and mannitol; and Compound A is present in the form of particles having a massmedian size (X50) of between (and including) 3 μm and 5 μm.In another embodiment, the pharmaceutical composition comprises Compound A,poloxamer P338, PVP, and mannitol and has the weight ratios (either pre-or post-reconstitution) as shown in table 1aa and 1ab. In an embodiment, the pharmaceuticalcomposition may further comprise a buffer solution In an embodiment the buffer solutionhas the ratios shown in table 1ac:Table 1aa Ingredient Ratio to compound ACompound A Poloxamer 338 1:25 to 1:35PVP K12 1:15 to 1:25Mannitol 1:5 to 1:12Table 1ab Ingredient Ratio to compound A Ratio to compound ACompound A Poloxamer 338 1:30 1:30PVP K12 1:20 1:20Mannitol 1:8.5 1:11.5Table 1ac

[0002] Ingredient Ratio to compound A Ratio to Compound ACompound A Citric acid1:400 1:350-450monohydrate Sodium citrate1:171.4 1:100-200dihydrate In another embodiment, the pharmaceutical composition, before lyophilisation andreconstitution, is as described in Tables 1a to 1e. In this embodiment, weights of eachcomponent are measured as mg / mL in a pre-lyophilised slurry:Table 1a Ingredient Concentration (mg / mL)Compound A 100 to 600 (X50 = 3 to 6 μm and X90 = 7 to 14 μm)Poloxamer 338 5 to 15PVP K12 5 to 20Mannitol 30 to 45Table 1b Ingredient Concentration (mg / mL)Compound A 100 to 600 (X50 = 3 to 6 μm and X90 = 7 to 14 μm)Poloxamer 338 5 to 15NaCMC 2 to 10Mannitol 30 to 45Table 1c Ingredient Concentration (mg / mL)Compound A 300 (X50 = 3 to 6 μm and X90 = 7 to 14 μm)Poloxamer 338 10PVP K12 15Mannitol 35 Table 1d Ingredient Concentration (mg / mL)Compound A 300 (X50 = 3 to 6 μm and X90 = 7 to 14 μm)Poloxamer 338 10NaCMC 5Mannitol 35Table 1eIngredient Concentration (mg / mL)Compound A, 400.0PVPK12 20.0Poloxamer 338 13.3Mannitol 35.0In an embodiment, the pharmaceutical composition, after reconstitution, is asdescribed in Tables 1f, 1g, 1h and 1i: Table 1fIngredient Concentration (mg / ml)Compound A, micronized 300.0 (X50 = 3 to 6 μm and X90 =7 to 14 μm)PVP K12 15.0Poloxamer 338 10.0Mannitol 35.0Table 1gIngredient Concentration (mg / mL)Compound A, micronized 350.0 (X50 = 3 to 6 μm and X90 =7 to 14 μm)PVP K12 17.5Poloxamer 338 11.7Mannitol 40.8Table 1hIngredient Concentration (mg / mL)Compound A, micronized 400.0 (X50 = 3 to 6 μm and X90 =7 to 14 μm)PVP K12 20Poloxamer 338 13.3Mannitol 46.7Table 1iIngredient Concentration (mg / mL)Compound A, micronized 450.0 (X50 = 3 to 6 μm and X90 =7 to 14 μm)PVP K12 22.5Poloxamer 338 15.0Mannitol 52.5In an embodiment the pharmaceutical composition of the invention has a pH of about 4 or greater. A pH of about 4 or more reduces pain to the patient if the composition is administered via injection. In an embodiment, the pharmaceutical composition of theinvention has a pH of between 4 and 5. In an embodiment, the pharmaceutical compositionof the invention comprises a buffer. As used herein, the term "buffer" means a bufferedsolution that resists changes in pH by the action of its acid- base conjugate components.The buffer may be any suitable buffer. In an embodiment, the buffer is an acetate buffer. Inan embodiment the acetate buffer is an acetate buffer solution comprising sodium acetatetrihydrate and acetic acid or glacial acetic acid. In another embodiment the buffer is a citrate buffer. In an embodiment the citrate buffer is a citrate buffer solution comprising citric acidmonohydrate and sodium citrate or trisodium citrate dihydrate. In an embodiment thepharmaceutical composition comprises a buffer solution comprising citric acid monohydrateand sodium citrate dihydrate. In an embodiment, the pharmaceutical composition comprisesabout 5 to about 10 mM of the buffer. In an embodiment the pharmaceutical composition comprises less than 3 mg / mL of the total buffer. In an embodiment the pharmaceutical composition comprises less than 2 mg / mL of the total buffer solution. In an embodiment thepharmaceutical composition comprises about 2.5 mg / mL of the total buffer solution. In anembodiment the ratio of buffer solution to Compound A is 1:100 to 1:200. In an embodimentthe ratio of buffer solution to Compound A is 1:110 to 1:170. In an embodiment the ratio ofbuffer solution to Compound A is about 1:120. In an embodiment the ratio of buffer solutionto Compound A is about 1:160. The amount of buffer solution is the combined amount of allbuffer components. Any of the exemplary embodiments in Tables 1a to 1i may comprise a buffersolution. In an embodiment, the embodiments in Tables 1a to 1h comprise a buffer solutioncomprising citric acid monohydrate and sodium citrate dihydrate. In these embodiments,the ratio of buffer solution to Compound A may be 1:100 to 1:200. In these embodimentsthe ratio of buffer solution to Compound A may be 1:110 to 1:170. In these embodimentsthe ratio of buffer solution to Compound A may be about 1:120. In these embodiments theratio of buffer solution to Compound A may be about 1:160. Methods of treatment In a second aspect, the present invention provides methods for (a) treatment of HIV infection in a human in need thereof comprising administering to said human a therapeutically effective amount of a pharmaceutical composition as defined herein; and (b) prevention of HIV infection in a human comprising administering to said human an effective amount of a pharmaceutical composition as defined herein. In one embodiment, the method comprises administering the pharmaceutical composition parenterally. In an embodiment, the pharmaceutical composition is administered intramuscularly. In an embodiment, the pharmaceutical composition is administered subcutaneously. In an embodiment the method comprises administering around 2mL to around 8 mLof the pharmaceutical composition to a patient. In an embodiment, the method comprises administering about 300 mg to about 3000 mg of Compound A to the human. In an embodiment the pharmaceutical composition is administered to a patient once every 4 to 18 months. In an embodiment, the pharmaceutical composition is administeredto the human once every 6 months to once every 12 months. In an embodiment, thepharmaceutical composition is administered once every 6 months. In an embodiment, thepharmaceutical composition is administered once every 7 months. In an embodiment, the pharmaceutical composition is administered once every 8 months. In an embodiment, the pharmaceutical composition is administered once every 9 months. In an embodiment, the pharmaceutical composition is administered once every 10 months. In an embodiment, the pharmaceutical composition is administered once every 11 months. In an embodiment, the pharmaceutical composition is administered once every 12 months. In an embodiment, the pharmaceutical composition may be administered by any suitable means. In one embodiment, the pharmaceutical composition may be administered subcutaneously. In this embodiment, the pharmaceutical composition may be administered subcutaneously by another (e.g., by a healthcare professional) or may be self-administered by a patient. In this embodiment the pharmaceutical composition may be administered subcutaneously via injection. In an embodiment the pharmaceutical composition isadministered subcutaneously via injection. In an embodiment the pharmaceutical composition is administered or self-administered once monthly by subcutaneous injection. In another embodiment, the pharmaceutical composition is administered or self- administered once every two months by subcutaneous injection. In another embodiment the pharmaceutical composition is administered intramuscularly via injection. In this embodiment, the pharmaceutical composition may be administered intramuscularly by another (e.g., by a healthcare professional) or may be self- administered by a patient. In an embodiment, the pharmaceutical composition is administered intramuscularly via injection once every 6 to 18 months. In another embodiment, the pharmaceutical composition is administered or self-administeredintramuscularly via injection once every 8 to 14 months. In another embodiment, thepharmaceutical composition is administered or self-administered intramuscularly viainjection once every 12 months. In an embodiment, the pharmaceutical composition isintramuscularly administered in one injection during a visit with a healthcare professional. In an embodiment the pharmaceutical compositions of the present invention are administered in combination with other pharmaceutical compositions as a component of a multi drug treatment regimen. In an embodiment, the other pharmaceutical compositionsare drugs which treat or prevent HIV infection. Marketed medicines are currently availableto treat HIV infection.Medical Use In a third aspect, the present invention provides a pharmaceutical compositiondefined herein for use in the treatment or prevention of HIV infection.In one embodiment the use comprises administering the pharmaceutical composition parenterally. In one embodiment, the pharmaceutical composition is suitable for use as an injectable composition. In an embodiment the use comprises administering the pharmaceutical composition intramuscularly. In another embodiment the use comprises administering the pharmaceutical composition subcutaneously. In one embodiment, the use comprises administering the pharmaceutical composition parenterally. In an embodiment, the pharmaceutical composition is administered intramuscularly. In an embodiment, the pharmaceutical composition is administered subcutaneously. In an embodiment the use comprises administering around 2 mL to around 10 mLof the pharmaceutical composition to a patient. In an embodiment, the use comprises administering about 300 mg to about 3000 mg of Compound A to the human. In an embodiment the pharmaceutical composition is administered to a patient once every 4 to 18 months. In an embodiment, the pharmaceutical composition is administered to the human once every 6 months to once every 12 months. In an embodiment, the pharmaceutical composition is administered once every 6 months. In an embodiment, the pharmaceutical composition is administered once every 7 months. In an embodiment, the pharmaceutical composition is administered once every 8 months. In an embodiment, the pharmaceutical composition is administered once every 9 months. In an embodiment, the pharmaceutical composition is administered once every 10 months. In an embodiment, the pharmaceutical composition is administered once every 11 months. In an embodiment, the pharmaceutical composition is administered once every 12 months. In an embodiment, the pharmaceutical composition may be administered by any suitable means. In one embodiment, the pharmaceutical composition may be administered subcutaneously. In this embodiment, the pharmaceutical composition may be administered subcutaneously by another (e.g., by a healthcare professional) or may be self-administeredby a patient. In this embodiment, the pharmaceutical composition may be administeredsubcutaneously via injection. In an embodiment the pharmaceutical composition isadministered subcutaneously via injection. In an embodiment, the pharmaceuticalcomposition is administered or self-administered once monthly by subcutaneous injection. In another embodiment, the pharmaceutical composition is administered or self- administered once every two months by subcutaneous injection. In another embodiment the pharmaceutical composition is administered intramuscularly via injection. In this embodiment, the pharmaceutical composition may be administered intramuscularly by another (e.g., by a healthcare professional) or may be self- administered by a patient. In an embodiment of the invention, the pharmaceutical composition is administered intramuscularly via injection once every 6 to 18 months. In another embodiment, the pharmaceutical composition is administered or self-administered intramuscularly via injection once every 8 to 14 months. In another embodiment, the pharmaceutical composition is administered or self-administered intramuscularly via injection once every 12 months. In an embodiment, the pharmaceutical composition is intramuscularly administered in one injection during a visit with a healthcare professional. In an embodiment the pharmaceutical compositions of the present invention are administered in combination with other pharmaceutical compositions as a component of a multi drug treatment regimen. In an embodiment, the other pharmaceutical compositionsare drugs which treat or prevent HIV infection. Marketed medicines are currently availableto treat HIV infection.Manufacture of a Medicament In a fourth aspect the present invention provides a pharmaceutical composition as described herein, in the manufacture of a medicament for treatment or prevention of HIVinfection. The medicament for treatment or prevention of HIV infection can be as describedherein above. Kits In a fifth aspect the present invention provides a kit comprising Compound A as alyophilised powder. In an embodiment the kit comprises a syringe or vial comprising a composition of the invention as well as a leaflet comprising use instructions. In an embodiment the present invention provides a method of preparing areconstituted suspension, the method comprising providing the kit as described herein andcontacting the lyophilized composition with a suitable liquid to produce a reconstituted solution. In an embodiment the suitable liquid is an aqueous solvent. In an embodiment the suitable liquid is water. In another embodiment the suitable liquid is a non-aqueous solvent. The following non-limiting embodiments illustrate the present invention: EMBODIMENTS Embodiment 1 (E1). A pharmaceutical composition comprising Compound A, , E2. The pharmaceutical composition according to embodiment 1, wherein Compound A is present at a concentration of 100 to 600 mg / mL. E3. The pharmaceutical composition according to embodiment 1 or embodiment 2, wherein the poloxamer is P188, P338 or P407.E4. The pharmaceutical composition according to embodiment 3, wherein the poloxamer isP338. E5. The pharmaceutical composition according to any preceding embodiment, wherein the poloxamer is present at a concentration of 5 to 15 mg / mL. E6. The pharmaceutical composition according to any preceding embodiment, wherein the weight ratio of the poloxamer to Compound A is about 1:30. E7. The pharmaceutical composition according to any preceding embodiment, wherein the composition further comprises: a stabilizer; and a tonicity adjuster.E8. The pharmaceutical composition according to embodiment 7, wherein the stabiliser ispresent at a concentration of 5 to 15 mg / mL.E9. The pharmaceutical composition according to embodiment 7 or 8, wherein the tonicityadjuster is present in a concentration of 30 to 35 mg / mL.E10. The pharmaceutical composition according to any one of embodiment 7 to 9, whereinthe weight ratio of tonicity adjuster to Compound A is about 1:8.5.E11. The pharmaceutical composition according to any one of embodiment 7 to 10, whereinthe tonicity adjuster is selected from the group consisting of mannitol, sorbitol, lactose, trehalose, raffinose, dextrose, maltose, galactose, sucrose, and polysucrose.E12. The pharmaceutical composition according to embodiment 11, wherein the tonicityadjuster is mannitol.E13. The pharmaceutical composition according to any one of embodiment 7 to 12, whereinthe stabilizer is selected from the group consisting of sodium carboxymethylcellulose (NaCMC), polyvinylpyrrolidone (PVP), polyethylene glycol 3350 and polyethylene glycol 4000.E14. The pharmaceutical composition according to embodiment 13, wherein the stabilizeris sodium carboxymethylcellulose (NaCMC).E15. The pharmaceutical composition according to embodiment 14, wherein the weight ratioof NaCMC to Compound A is about 1:60.E16. The pharmaceutical composition according to embodiment 14 or 15, wherein thepoloxamer is P338, the stabiliser is NaCMC and the tonicity adjuster is mannitol; and Compound A is present in the form of particles having a mass median size (X50) of between(and including) 1 μm and 15 μm.E17. The pharmaceutical composition according to embodiment 16, wherein thepharmaceutical composition comprises Compound A in an amount of 30 %w / v, mannitol in an amount of 3.5 % w / v, P338 in an amount of 1 % w / v, and NaCMC in an amount of 0.5 % w / v.E18. The pharmaceutical composition according to embodiment 16 wherein mannitol ispresent at a weight ratio of mannitol to Compound A of about 1:8.5; poloxamer is present at a weight ratio of poloxamer to Compound A of about 1:30; and NaCMC is present at a weight ratio of NaCMC to Compound A of about 1:60.E19. The pharmaceutical composition according to embodiment 13, wherein the stabilizeris polyvinylpyrrolidone (PVP).E20. The pharmaceutical composition according to embodiment 19, wherein the PVP isPVP K12.E21. The pharmaceutical composition according to embodiment 19 or 20, wherein theweight ratio of PVP to Compound A is about 1:20.E22. The pharmaceutical composition according to any one of embodiment 19 to 21,wherein the poloxamer is P338, the stabiliser is PVP, the tonicity adjuster is mannitol and Compound A is present in the form of particles having a mass median size (X50) of between(and including) 1 μm and 15 μm.E23. The pharmaceutical composition according to embodiment 22, wherein thepharmaceutical composition comprises Compound A in an amount of 30 % w / v, mannitol in an amount of 3.5% w / v, P338 in an amount of 1% w / v, and PVP in an amount of 1.5 % w / v.E24. The pharmaceutical composition according to embodiment 22 wherein mannitol ispresent at a weight ratio of mannitol to Compound A of about 1:8.5; poloxamer is present at a weight ratio of poloxamer to Compound A of about 1:30; and PVP is present at a weight ratio of PVP to Compound A of about 1:20.E25. The pharmaceutical composition according to any preceding embodiment, whereinCompound A is present in the form of particles having a mass median size (X50) of between(and including) 1 μm and 15 μm.E26. The pharmaceutical composition according to embodiment 25, wherein the particleshave a mass median size (X50) of between (and including) 1 μm and 15 μm.E27. The pharmaceutical composition according to embodiment 26, wherein the particleshave a mass median size (X50) of between (and including) 3 μm and 6 μm.E28. The pharmaceutical composition according to any one of embodiment 25 to 27 whereinthe particles have an X90 value of between (and including) 7 μm and 14 μm provided that X90 is greater than X50.E29. The pharmaceutical composition according to any one of embodiment 25 to 28,wherein the particles have an X10 value of between (and including) 1.5 μm and 3 μm provided that X10 is lower than X50. E30. The pharmaceutical composition according to any preceding embodiment, wherein the composition is in the form of a lyophilised powder.E31. The pharmaceutical composition according to any of embodiment 1 to 29 wherein thecomposition is: (a) reconstituted from a lyophilized powder with a suitable liquid; or (b) provided as a liquid formulation.E32. The pharmaceutical composition according to embodiment 31, wherein the suitableliquid is an aqueous solvent.E33. The pharmaceutical composition according to embodiment 32, wherein the aqueoussolvent is water.E34. The pharmaceutical composition according to embodiment 32, wherein the suitableliquid is a non-aqueous solvent.E35. The pharmaceutical composition according to any one of embodiment 1 to 34, whereinthe pharmaceutical composition is formulated as a parenteral pharmaceutical composition.E36. The pharmaceutical composition according to embodiment 35, wherein thepharmaceutical composition is suitable for injection.E37. The pharmaceutical composition according to embodiment 36, wherein thepharmaceutical composition is suitable for subcutaneous or intramuscular injection. E38. A method of treating human immunodeficiency virus (HIV) infection in a human in need thereof comprising administering to said human a therapeutically effective amount of thepharmaceutical composition according to any one of embodiment 1 to 37.E39. A method of preventing human immunodeficiency virus (HIV) infection in a human in need thereof comprising administering to said human an effective amount of thepharmaceutical composition according to any one of embodiment 1 to 37.E40. The method according to embodiment 38 or 39, wherein the pharmaceuticalcomposition is administered to the human via an injection.E41. The method according to embodiment 40, wherein the injection is administeredintramuscularly (IM).E42. The method according to embodiment 40, wherein the injection is administeredsubcutaneously (SC).E43. The method according to any one of embodiment 38 to 42, wherein about 300 mg toabout 3000 mg of Compound A is administered to the human.E44. The method according to any one of embodiment 38 to 43, wherein the methodcomprises administering the pharmaceutical composition to the human once every 4 to 18 months.E45. The method according to embodiment 44, wherein the method comprisesadministering the pharmaceutical composition to the human once every 6 to 12 months.E46. The pharmaceutical composition according to any one of embodiment 1 to 37, for usein therapy.E47. The pharmaceutical composition according to any one of embodiment 1 to 37 for usein treatment or prevention of human immunodeficiency virus (HIV) infection.E48. The pharmaceutical composition for use according to embodiment 47, whereinadministration of the pharmaceutical formulation is via an injection.E49. The pharmaceutical composition for use according to embodiment 47, wherein theinjection is administered intramuscularly (IM).E50. The pharmaceutical composition for use according to embodiment 47, wherein theinjection is administered subcutaneously (SC).E51. The pharmaceutical composition for use according to any one of embodiment 46 to50, wherein 2 mL to 10 mL of the composition or the pharmaceutical composition is administered to a human.E52. The pharmaceutical composition for use according to any one of embodiment 46 to51, wherein about 300 mg to about 3000 mg of Compound A is administered to a human.E53. The pharmaceutical composition for use according to any one of embodiment 56 to52, wherein the use comprises administering the pharmaceutical composition to the human once every 4 to 18 months.E54. The pharmaceutical composition for use according to embodiment 53, wherein the usecomprises administering the pharmaceutical composition to the human once every 6 to 12 months.E55. Use of the pharmaceutical composition according to any one of embodiment 1 to 37,in the manufacture of a medicament for treatment of human immunodeficiency virus (HIV) infection. E56. A kit comprising a container comprising the pharmaceutical composition according toany one of embodiment 1 to 37 as a lyophilised powder.E57. A method of preparing a reconstituted solution, the method comprising providing thekit according to embodiment 56; and contacting the lyophilised powder with a suitable liquidto produce the reconstituted suspension.E58. The method according to embodiment 57, wherein the suitable liquid is an aqueoussolvent.E59. The method according to embodiment 57 or embodiment 58, wherein the suitableliquid is water.E60. The method according to embodiment 59, wherein the suitable liquid is a non-aqueous solvent. The following non-limiting examples illustrate the present invention. EXAMPLES Example 1: Preparation of Form 1 of Compound A without seeding Aslurry of (3S,11AR)-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7- dioxo-2,3,5,7,11,11a-hexahydrooxazolo [3,2-a] pyrido[1,2-d]pyrazine-8-carboxamide (1 g, 2.467mmol) and stearoyl chloride (0.897 g, 2.96 mmol) in N,N-Dimethylacetamide (DMA) (10 mL) at room temperature in a 20 mL scintillation vial fitted with thermocouple and magnetic bar. Hunig's base (0.517 mL, 2.96 mmol) was then added, over approximately 15 seconds at room temperature over stirring. Upon adding the base (at 22.5 C), an exotherm wasobserved where the temperature increased to 30.5 C, within 3 minutes, then stabilized anddecreased back to room temperature (22.5 C) within 5 minutes, all during which time thereaction mixture thickened up but remained a stirrable slurry. The suspension was thenheated to 55 °C where all almost all solids dissolved, at 60°C a solution (light orange incolor) formed. After cooling to room temperature (+21°C), 5 vol% of water (0.5 mL) wasslowly added, at room temperature stirring was continued to induce crystallisation (for 15 minutes). This material was stirred for an additional hour. The solids were subsequently filtered off and rinsed with excess amounts of acetonitrile.The solid (48.5 mg) was then added to cyclopentyl methyl ether (1.5 ml). A pourablesuspension was made, then filtered producing a clear filtrate. The filter funnels with products were placed into vacuum oven at ambient temperature, loosely covered, under vacuum with slight air purge. Solid was placed in the oven overnight (25 hrs). After drying, the material was characterized using DSC (Fig. 9) and XRPD (Fig. 8). The DSC showed an onsettemperate of 118.0oC and a peak temperature of 120.4oC characteristic of Form 1. Fig.9 shows an XRPD of the material produced from the above method (top line), an XRPD ofGroup B of Compound A (middle line) and an XRPD of Form 1 of Compound A (bottom line), showing that the XRPD of the material produced from the above method is characteristic of Form 1. Example 2: (3R,6S)-12-{[(2,4-difluorophenyl)methyl]carbamoyl}-6-methyl-8,11-dioxo-4- oxa-1,7-diazatricyclo[7.4.0.0³,⁷]trideca-9,12-dien-10- octadecenoate In a reactor, stearic acid (1.6 equiv) was slurried in dicholoromethane (3.8 vol) at 22- 28 °C at a 200 gallon scale, with input material amounting to 13.1 kg of cabotegravir. Oxalylchloride (1.76 equiv) was added slowly over no less than 3 h at 22-28 °C. The reaction mixture was then stirred at 22-28 °C for no less than 6 h, and concentrated to 3.5 vol under slight vacuum with solution temperature controlled below 50 °C. The solvent was swapped to toluene (5.5 vol) via vacuum distillation with solution temperature controlled below 50 °C and again concentrated to 3.5 vol. N-Methylpyrrolidone (10 vol) and cabotegravir (1.00 equiv) were charged to the above stearoyl chloride solution, and the mixture was heated to 62-68 °C. N,N- Diisopropylethylamine (2.01 equiv) was added over no less than 1 h. The mixture was stirred for no less than 30 min. Water (2.5 vol) was charged over no less than 10 min while maintaining reaction temperature at 62-68 °C, and then methanol (10 vol) was charged over no less than 30 min at the same temperature. Compound A seed was slurried in methanol, and then this methanol seed slurry was charged to the reaction mixture at 47-49 °C. Theaddition of this Compound A seed was to control nucleation and crystal growth to ensuregood manufacturability and uniformity, but the addition of seed was not required to synthesize Compound A. The mixture was held at this temperature for no less than 4 h to allow crystals to grow slowly. The reaction mixture was cooled to 17-23 °C at 0.1 °C / min, and then held at 17-23 °C for no less than 2 h. The slurry was then filtered in a filter dryer, washed with the crystallization composition solvents (2.04 vol N-Methylpyrrolidone, 2.04 vol methanol, 0.51 vol toluene, and 0.41 vol water) and then filtered. The wet cake was reslurried in methanol (12 vol) for at least 1 h and then filtered. Next, the wet cake was reslurried in 14 vol cyclohexane twice at 17-23 °C for at least 1 h each time and then filtered. The slurry wassampled and nuclear magnetic resonance (NMR) analysis was used to confirm the stearicanhydride is ≤ 6.0 wt%. The wet cake was then washed with 7 vol cyclohexane and then filtered. Nitrogen was passed through the wet cake for not less than 1 h. The product was then dried at 45-50 °C under vacuum. The product (intermediate grade Compound A) wasoffloaded from a filter dryer once the loss on drying of a sample showed ≤ 3.0% weightchange after 10 minutes at 110 °C. Material that was synthesised was predominantly form1 once dried. Yielding 19.9 kg of Compound A.Example 2b In a crystallizer at a 200 gallon scale, with input material amounting to 19.9 kg ofintermediate grade compound A, intermediate grade Compound A obtained from Stage 1 was dissolved in cyclopentyl methyl ether at 57-63 °C. The solution was clarified by filtration to remove any potential particulates. Solution temperature was then decreased to 38-42 °C. The solution was seeded with 1.0% w / w Compound A of the primarily Form 1 crystal form. Before adding the seed to the crystallizer, the seed was slurried in isopropyl alcohol. The mixture was held for 30 minutes at the seeding temperature. The slurry was then cooled to 12-18 °C at 0.1 °C / min. The slurry was held at 12-18 °C for no less than 4 h. The slurry was then transferred to a filter dryer at 12-18 °C. Cyclopentyl methyl ether (4 vol, filtered) was used to rinse the cold crystallizer, and the rinse was transferred to the filter dryer to wash the wet cake. The cake wash was filtered. Cyclohexane (10 vol, filtered) was charged to the filter dryer and then agitated to suspend. Cyclopentyl methyl ether (4 vol, filtered) was transferred to thefilter dryer to wash the wet cake once more. A sample of the wet cake in the filter dryer wastaken and dried in a lab vacuum oven. XRPD, NMR, and DSC analysis were performed onthe dried sample. XRPD, NMR, and DSC analyses were performed on the dried sample. Ifthe DSC and XRPD analyses were not consistent with Group D, Group E, or a mixture ofthe two forms, and / or NMR analysis showed stearic anhydride levels < 0.5 wt%, anadditional cyclohexane reslurry wash (10 vol, filtered) and CPME wash (4 vol filtered) wasperformed. The cake was dried in the filter dryer at 40 °C under vacuum until a well-blended sample showed ≤ 3.0% weight change after 10 minutes at 120 °C, and XRPD and DSC indicated that the product was Form 1. The DSC thermogram of Form 1 of Compound A was recorded on a TA Instruments Q100 Differential Scanning Calorimeter equipped with an autosampler is shown in Fig.2.The experiments were conducted using a heating rate of 10 °C / min in a crimped aluminumpan. The DSC thermogram of Form 1 of Compound A exhibits a single endotherm with an onset temperature of about 120 °C. The thermogravimetric analysis (TGA) thermogram of Form 1 of Compound A was recorded on a TA Instruments Q500 Thermogravimetric Analyzer and is shown in Fig.3. The XRPD of Form 1 of Compound A obtained after Example 2b is shown in Fig.10. Example 2c At room temperature, 10 vols of acetone were added to Compound A.The mixture was stirred and heated to 50°C until full dissolution occurred. Themixture was polish filtered while warm and transferred to a clean vessel. The mixture wascooled from 50°C to 20°C at a rate of 0.1°C / min. At 20°C, the mixture was seeded with~2 mg of Form 1 of Compound A. The mixture was allowed to stir for 30 mins at 20°C. Themixture was continued to cool to 10°C at a rate of 0.1°C / min and held at that temperatureovernight (~16 hrs). The mixture was then filtered. The cake was analysed by PXRD (Fig.21) and DSC (Fig. 20) and found to be consistent with Form 1. The cake was then dried ina vacuum oven overnight at 40°C. The process in example 3c may be beneficial in manufacturing as it reduces the number of steps required to get to Form 1.Example 2d – Preparation of Group B of Compound A from the impurities of a drugsubstance process and form 1 Compound A, as prepared in example 2b, was slurried in 20 volumes of ethanol and 8 wt% weight of stearic anhydride was added to the vessel and was slurried until solid formation occurred. The slurry was vacuum filtered until the solid was solvent free. No wash was performed. The solid was placed in a vacuum oven at 40°C under vacuum and nitrogen purge to dry material further. The differential scanning calorimetry (DSC) thermogram of Group B of Compound A as prepared in this example was recorded on a TA Instruments Q100 Differential Scanning Calorimeter equipped with an autosampler and a refrigerated cooling system under N2 purge and is shown in Fig.14. The experiments were conducted using a heating rate of 10 °C / min in a crimped aluminum pan. The DSC thermogram of Group B of Compound A exhibits two endotherms; the first endotherm has an onset temperature at 87°C and the second endotherm has an onset temperature at 121 °C.Example 2e – Mixtures of Group B and Form 1A mixture of Form 1 and Group B of a ratio of 50:50 was formed by physically mixing Form 1 (made using the methods stated in Example 2a and 2b) and Group B (made by the methods stated in Example 6). A mixture of Form 1 and Group B of a ratio of 70:30 was formed by physically mixing Form 1 (made using the methods stated in Example 3a and 3b) and Group B (made by the methods stated in Example 2d). A mixture of Form 1 and Group B of a ratio of 90:10 was formed by physically mixing Form 1 (made using the methods stated in Example 3a and 3b) and Group B (made by the methods stated in Example 2d). Pure group B was formed by the method stated in Example 2d. Pure Form 1 was formed by the method stated in Example 2b, it was then purified to remove all chemical impurities using preparative chromatography. XRPDs were taken of the mixtures and pure group B and Form 1. These XRPDs areoverlayed and shown in Fig. 15 where top to bottom is (50:50, 70:30, 90:10, 95:5 Form 1:Grp B), second from the bottom pure Grp B, bottom pure Form 1. The portions of the XRPD indicating the presence of group B in the mixtures are in therange 6.0 to 7.0 °2θ and in the range of 21.0 to 22.0 °2θ. Separate overlayed XRPDs areshown in higher resolution in the ranges of 4.5 to 9.5 °2θ (Fig. 16) and 19.0 to 24.5 °2θ(Fig. 17). The presence of additional peaks at about 6.75, 7.25, and 21.6 °2θ in pure GroupB leads to shouldering and less defined peaks in the range of 6.0 to 7.0 °2θ and in the range of 21.0 to 22.0 °2θ. spectra in mixtures of Group B and Form 1. Example 3: Pharmaceutical CompositionsIngredient Concentration measuredpre lyophilization and pre- reconstitution (mg / mL)Compound A, micronized 300.0Polyvinyl pyrrolidone K12 15.0Poloxamer 338 10.0Mannitol 35.0Table 1 Table 1 shows an exemplary pharmaceutical composition of the invention (pharmaceutical compositions are also described in these examples as “suspensions”), which was made using the following method: A formulation vehicle was prepared by dissolving / diluting 15 g Poloxamer 338(P338) (BASF, Kolliphor P338) in about 1050 g water. After P338 is fully dissolved in waterfor injection (WFI), 22.5 g Polyvinyl pyrrolidone K12 (PVP K12) (Ashland, Plasdone C-12) was added until fully dissolved. Lastly, 52.5 g mannitol (Roquette Freres) was dissolved in the solution. The bulk vehicle was then filtered through a 0.22 μm filter.300 g Compound A micronized API (target X50 = 3-5μm particle size) was divided equally and added to 710 g filtered vehicle one aliquot at a time. For each aliquot of API added, suspension was vacuum de-aerated for approximately 10 minutes and then stirred until API completely submerged into the vehicle. Once the full amount of API was added, 50 g of vehicle was used to rinse off the residual API left in the vessels. The suspension then continued to stir and vacuum de-aerate overnight. If there was any volume loss during overnight vacuum de-aeration, the amount lost was made up for with the appropriate amount of WFI added back into suspension. After stirring for approximately 30 minutes, the suspension was measured fordensity. Once target density (1.06 g / mL) was reached, the suspension proceeded to behomogenized (may be filtered) and was then filled into vials.The product was lyophilized by freezing at -45°C for 185 minutes, annealing at - 18°C for 207 minutes, refreezing at -45°C for 207 minutes (each transition at a ramp rate of+ / - 1°C / min), primary drying at -10°C (ramp rate: 0.175°C / min) for approximately 24 hoursat approximately 150 mTorr, and secondary drying at 25°C (ramp rate: 0.145°C / min) for at least 10 hours at approximately 150 mTorr. The lyophilized vials were backflushed with nitrogen to about 650 Torr, sealed, and sterilized by gamma irradiation at a minimum doseof 25kGy. The formulation is reconstituted with WFI and briefly shaken to resuspend priorto administration. The lyophilized cake was reconstituted by injecting 1.7 mL of WFI into the vial. Thevial was then reconstituted with a 10-second interval quick wrist movement. This action was repeated until the bottom of the vial was clear, and the cake was fully dissolved into a suspension. Table 2 Ingredient Concentration (mg / mL)Compound A, micronized 350.0Polyvinyl pyrrolidone K12 17.5Poloxamer 338 11.7Mannitol 40.8Table 2 shows a lyophilized suspension reconstituted at drug concentration of 350mg / mL. The lyophilized cake (manufactured at 300 mg / mL above) can be reconstituted tohigher drug concentrations by reconstituting with a smaller quantity of WFI. To get a 350mg / mL drug load, 1.3 mL of WFI was injected into the vial. The vial was then reconstitutedwith a 10-second interval quick wrist movement. The action is repeated until the bottom ofthe vial was clear, and the cake fully dissolved into a suspension.Table 3 Ingredient Concentration (mg / mL)Compound A, micronized 400.0Polyvinyl pyrrolidone K12 20Poloxamer 338 13.3Mannitol 46.7Table 3 shows a lyophilized suspension reconstituted at drug concentration of 350mg / mL. To get a 400 mg / mL drug load, the powder was reconstituted in the vial with 1.1 mLof WFI. The vial was then reconstituted with a 10-second interval quick wrist movement.The action was repeated until the bottom of the vial was clear, and the cake fully dissolvedinto a suspension. Table 4 Ingredient Concentration (mg / mL)Compound A, micronized 300.0Sodium Carboxymethylcellulose 5.0Poloxamer 338 10.0Mannitol 35.0Table 4 shows an exemplary pharmaceutical composition of the invention whichwas made using the following method: A formulation vehicle was prepared by dissolving / diluting 7.2 g Poloxamer 338(BASF, Kolliphor P338) in about 518.4 g water for injection (WFI). After P338 was fullydissolved in WFI, 3.6 g of Sodiumcarboxymethylcellulose (NaCMC) (Ashland, AqualonCMC 7L2P) was added until fully dissolved. Lastly, 25.2 g mannitol (Roquette Freres) wasdissolved in the solution. The bulk vehicle was then filtered through a 0.22 μm filter. 180 gCompound A Micronized API (target X50 = 3-5μm particle size) was slowly added to 462 gof vehicle while stirring with vortex. The suspension then continued to stir overnight. Afterstirring overnight, the suspension was homogenized for 10 minutes at 10,000 rpm and then stirred at light speeds for 30 min for the suspension to de-aerate. Once the suspensionreached target volume (600 mL), the suspension (may be filtered) was then filled into vials.The product was lyophilized by freezing at -45°C for 185 minutes, annealing at - 18°C for 207 minutes, refreezing at -45°C for 207 minutes (each transition at a ramp rate of+ / - 1°C / min), primary drying at -10°C (ramp rate: 0.175°C / min) for approximately 24 hoursat approximately 150 mTorr, and secondary drying at 25°C (ramp rate: 0.145°C / min) for at least 10 hours at approximately 150 mTorr. The lyophilized vials were backflushed with nitrogen to about 650 Torr, sealed, and sterilized by gamma irradiation at a minimum doseof 25kGy. The formulation was reconstituted with WFI and briefly shaken to resuspend priorto administration. The lyophilized cake was reconstituted by injecting 1.7 mL of WFI into the vial. The vial was then reconstituted with a 10-second interval quick wrist movement. This action was repeated until the bottom of the vial was clear, and the cake was fully dissolved into a suspension. Example 4 Table 5 shows two exemplary compositions of the invention. Table 6 shows the stability of the composition in Batch 1 in Table 5. Table 7 shows stability of the composition shown asBatch 2 in Table 5. Methods for measuring stability of the composition are detailed below.Reconstitution time (Recon. Time) (sec): This was determined by adding the water for injection needed through the septum into the sample vial. The sample vial was then manually shaken with quick wrist motions in 10- second intervals until the lyophile cake was fully reconstituted. Resuspendability time (Resusp. Time) (sec) After reconstitution, the sample vial sat for approximately 2 hours, then was manually shaken for 10 seconds with quick wrist motions. The sample vial was inverted and checked to ensure the resuspension was uniform without any caking at the bottom of the vial. Shaking continued at 10-second intervals until fully resuspended. Content (% Label Claim) Content (% label claim) was calculated to confirm that the amount of Compound Ain the final composition compared to the amount expected to achieve – 90-110% isconsidered an acceptable amount. Standard solution of Compound A at a nominal concentration of 0.25 mg / mL was prepared for determining system suitability for content.For example, 25 mg of Compound A drug substance standard was accurately weighed intoa 100 mL volumetric flask and dissolved with 100% acetonitrile to volume with the aid of sonication. Compound A lyophile samples for content determination were prepared at a nominal concentration of 0.25 mg / mL in 100% acetonitrile solvent. Content was typically prepared in duplicate. The lyophile was reconstituted as detailed above (Reconstitution time (Recon. Time) (sec)). After reconstitution, the vial was decrimped and 0.167 mL of sample transferred directly into a tared 200 mL volumetric flask on an analytical balance and the accurate weight determined. Using 100% acetonitrile, the sample was dissolved to volume with the aid of sonication to ensure complete dissolution. Solutions were then filtered and transferred to HPLC vials for analysis per the instrument parameters below. Impurity (% Area) Sensitivity solution at 0.05% w / w of the nominal Compound A standard (0.25 mg / mL prepared in the Content section above) was prepared and analysed as part of the system suitability. For example, 50 L of 0.25 mg / mL Compound A reference standard solution was transferred into a 100 mL volumetric flask and diluted to volume with 100% acetonitrile. Samples for HPLC analysis were filtered and transferred into HPLC vials foranalysis per instrument parameters below.Column details Poroshell 120, SB-C8, 2.7 m, 4.6 x 150 mmPN 683975-906Column temperature 40°CMobile phase A 0.1% v / v TFA in waterMobile phase B 100% AcetonitrileFlow rate 1.0 mL / minGradient profile Time (minutes)% A % B 0 70 30 6.0 70 30 15.0 40 60 25.0 2 98 30.0 2 98 30.1 70 30 35 70 30Run time 35 minDetector wavelength 257 nmInjection volume 10 μLAutosampler wash solvent 100% AcetonitrilepH Determination pH is determined per USP<791> (official version as of 01-Nov-2020). Injection Force Testing Samples were analyzed to determine the extrusion force required to expel drug product through the selected administration components. Testing was performed via a Texture Analyzer TA-XT (Stable Micro Systems) utilizing a 3mL polypropylene syringe and 25G x 5 / 8” thin walled (TW) needle at a speed of 1.66mm / sec. XRPD (% Form 1) Group B was the only Group seen in any of the XRPD patterns therefore % Form 1 wascalculated by deducting the % amount of Group B from 100 %.The data was analyzed using HighScore Plus 4.8 (4.8.0.25518). The process used for data analysis is as follows: The XRPD pattern was opened in HighScore Plus software and a peak search conducted. Default parameters are used: Minimum Significance: 5.00; Minimum Tip Width Gonio: 0.05; Maximum Tip Width Gonio: 1.00; Peak base with Gonio: 2.00; Minimum 2nd Derivative. If the number of highlighted peaks and baseline fit appeared adequate, results were accepted. All reflections were then selected. A Profile Fit (Caglioti) was then conducted. An inspection that fitted profile matches of the raw data was conducted. The areas of select Group Bpeaks (6.9deg, 7.2deg, and 21.6deg 2theta) were normalised by the Group D peak (7.4deg2theta). The plot at 50% was then truncated for analysis of low Group B level quantities. The expressions obtained from the linear fit of wt% Group B vs peak area ratio were used to determine level of Group B in unknown sample. A linear fit to the origin (0,0) was extrapolated as there would be no Group B peaks in a pure Group D sample. Table 5Batch # Formulation1 Compound A 300 mg / mL; 1.0 w / v% P338; 1.5 w / v% PVPK12; 3.5 w / v%Mannitol; formulation reconstituted to 300 mg / mL Compound A2 Compound A 300 mg / mL; 1.0 w / v% P338; 0.5 w / v% NaCMC; 3.5 w / v%Mannitol. Formulation reconstituted to 300 mg / mL Compound ATable 6 Batch 1 Conten Storage Recon. Resusp. XRPD IF Impurity Time t (% Conditi time Time (% form PSD (μm) (25G) (% pH (months) Label on (sec) (sec) 1) (N) Area)1Claim) Initial postX10 – 2.2;gamma0 10; 10 N / A  100 X50 – 5.1; N / A 101.6 0.81 4.27irradiatX90 – 11.0ion X10– 2.2;1 10; 10 10; 10 > 95 X50 – 5.2; 8.44 103.5 0.96 4.03X90– 11.5X10 – 2.2;X50 – 5.2;3 10; 10 N / A > 95 N / A 104.2 0.72 4.04X90 –25 °C 11.1 X10 – 2.2;6 10; 10 10; 10 > 95 X50- 5.2; 7.11 102.3 0.82 4.20X90- 11.6X10 – 2.3;9 10; 10 10; 10 > 95 X50 – 5.3; 5.25 99.5 0.78 3.56X90 – 11.7X10 – 2.2;X50 –1 10; 10 10; 10 > 95 8.36 103.8 0.97 4.065.2; X90 –11.5 40 °C X10 – 2.3;X50 – 5.3;3 10; 10 10; 10 > 95 18.79 103.8 0.72 4.18X90 –11.7X10 – 2.2;6 10; 10 10; 10 > 95 X50 – 5.2; 21.63 102.6 0.73 4.21X90- 11.4X10– 2.3;1 10; 20 10; 10 > 95 X50 – 5.2; 20.05 103.6 0.89 4.29X90– 11.050 °C X10 – 2.3;3 10; 10 10; 10 > 95 X50– 5.4; 16.76 103.7 0.71 4.23X90 – 11.51Cabotegravir is less than 1% at all temperature conditions and timepoints. Table 7 Batch 2 XRPD Recon. IF Content Impurity Storage Time (% PSD Time (25G) (% Label (% pH Condition (months) form (μm) (sec) (N) Claim)Area) 11) Initial postX10 - 2.0;130; 10;gamma 0 90X50 - 4.1; 17.0 102.8 1.5 6.2410; 10; 10 irradiationX90 - 9.5X10 - 1.9;1 40; 140 92.5 X50 - 4.1; N / A 108.9 1.3 6.19X90 - 9.4X10 – 2.0;25 °C6 30; 30; 30 93.2 X50 – 4.1; N / A 108.2 1.3 6.04X90 – 9.6X10 – 2.0;12 10; 20; 20 90 X50 – 4.1; 29.6 102.8 1.4 6.05X90 – 10X10 – 2.0;1 30; 70 91.7 X50 – 4.1; N / A 107.4 1.3 5.98X90 - 1040 °C X10 – 2.0;3 60; 90 88 X50 – 4.1; N / A 102.9 1.2 6.00X90 – 9.5X10 – 2.0;6 30; 30; 30 90.6 X50 – 4.2; N / A 105.4 1.3 5.90X90 – 9.9X10 – 2.0;1 40; 60 89.2 X50 - 4.1; N / A 108.7 1.4 6.09X90 - 9.550 °C X10 – 2.0;3 60; 60 87 X50 – 4.1; N / A 102.4 1.3 6.14X90 – 9.51Cabotegravir is less than 1% at all temperature conditions and timepoints.Note: Resuspension Time was not tested for Batch 2.Example 5 – Preclinical assessment of compositions. Comparison of formulations ofCompound A and Cabotegravir In this preclinical assessment, compositions of Compound A were compared to acomposition of cabotegravir (compositions shown in Table 8). Formulations were dosed in5 Sprague Dawley male rats per group at 75mg / Kg of Compound A in the intramuscularspace of the thigh (hindlimb). One nanosuspension formulation of Cabotegravir at200mg / mL (group 1) and two formulations of Compound A at 300mg / mL, one at micronparticle size (group 2, Lyophile), and the other at nano particle size (group 3, wet-beadmilled suspension), also differing in excipient composition, were administered intramuscularly through a single injection at target dose of 45mg / kg of Cabotegravirequivalents (corresponding to 75mg / Kg effective Compound A dose), in each rat. Details ofthe formulations are described in table 8.Micron size formulation dosed in group 2 was manufactured following procedure described in Example 2 and composition listed in Table 4. Nano size formulation dosed in group 3 was prepared dissolving 11.4 g of P338 in204.0 g of WFI. Once the P338 was fully dispersed, 9.7 g of PS20, 8.9 g of PEG 3350, and 9.7 g of Mannitol was added to the solution and stirred until fully dissolved. The bulk vehiclewas then filtered through a 0.22 μm filter. 75.0 g Compound A was then added to 187.5 gof filtered vehicle. The suspension was stirred for approximately three days before milling. The suspension was then milled for 45 minutes, reaching 200 nm at x50. Table 8 API Particle sizeGroup APIConcentration distribution Formulation composition (mg / mL) (μm)x10 x50 x902% Polysorbate 20, 2% 1Cabotegravir 200.6 0.10 0.23 0.60Polyethylene Glycol 3350, 3.5% Mannitol 1% Poloxamer 338, 0.5% 2Compound A 300 2.0 4.1 9.5Carboxymethycellulose sodium; 3.5% Mannitol 3.0 % Polysorbate-20, 3.5% 3Compound A 300 0.17 0.46 3.9Poloxamer 338, 2.73% Polyethylene Glycol 3350; 3% Mannitol Table 9 shows Cabotegravir plasma pharmacokinetics for the preclinical study and statistical analysis through t-test for several pharmacoKinetics (PK) parameters. Comparing Cabotegravir and Compound A nanoformulations (groups 1 and 3, respectively), Compound A produces a significantly reduced Cmax(3.7 folds) and extended t1 / 2(5.3 folds). Importantly, lyophile formulation from Group 2 highlights a reduced Cmax(13 folds) and extended t1 / 2(25 folds) compared to Cabotegravir formulation from Group 1. In addition, Lyophile formulation from Group 2 demonstrates reduced Cmax(3.7 folds) and extended t1 / 2(4.7 folds) comparedto nano formulation from Group 3. These results indicate that lyophile formulation ofCompound A (Group 2) may achieve an extended long-acting profile compared to otherformulations. Group 2 lyophile formulation may therefore be able to be dosed at less-frequent intervals. A comparison on both formulations using XRPD showed the difference between the two processes undertaken to produce the drug product. Both formulations were analysed following gamma irradiation. The presence of Group B is far more pronounced when compared to the lyophile formulation. A comparison of the two formulations was conducted at an initial timepoint, as soon as the material was irradiated. Fig. 7 shows an XRPD comparing Group 3 (bottom line on the figure) and Group 2(top line on the figure). Both XRPDs were run straight after gamma irradiation of thecompositions. The presence of Group B is far more pronounced in the wet bead milledcomposition compared to the lyophilized composition meaning that more Group B ofCompound A is present. Lyophilized Group 2 is > 95% Form 1 of Compound A.Table 9 CmaxTmaxt1 / 2AUClastAUCinf(ng / mL) (h) (h) (h) (h*μg / mL)Mean 76.2 268.8 243.6 43620.0 43820.0Group 1 – Cabotegravirnano (45mg / Kg IM) SD2 15.3 92.0 41.7 8995.1 9175.9Group 2 – Compound A Mean 5.7 739.2 6114.0 10266.0 49000.0Lyo (75mg / Kg IM)1SD2 1.0 552.1 2219.0 1146.0 12431.2Group 3 – Compound Mean 20.9 336.0 1300.0 27600.0 42060.01Anano (75mg / Kg IM)SD2 4.2 0.0 180.6 5244.5 9873.3G1 vs G2 **** * *** **** 0.237p value3G1 vs G3 **** 0.071 **** **** 0.389G2 vs G3 **** 0.071 *** **** 0.1781Corresponding to 45mg / Kg CAB-equivalents2SD: Standard Deviation3p value calculated from one-tailed unpaired t-test for significance: * = 0.01<p<0.05; ** = 0.001<p<0.01; *** = 0.0001<p<0.001; **** = p<0.0001 Legend: Cmax: Maximum plasma concentration; Tmax: time to reach maximum concentration; T1 / 2: half-life; AUClast: area under the plasma concentration-time curve to the last measurable plasma concentration; AUClast: area under the plasma concentration-time curve extrapolated to infinity; h: hours; ng: nanograms; μg: microgramsExample 6 - Comparison of Compound A composition PKComposition preparation of Compound A is described above. In this preclinicalassessment, two formulations of Compound A (Table 10) were dosed subcutaneously (SC)in three Sprague Dawley male rats per group at 75mg / Kg of Compound A with a singlebolus injection into the right interscapular region. Both lyophilized products were reconstituted with water for injection at 300mg / mLCompound A and were administered SC through a single injection at target dose of 45mg / kgof Cabotegravir equivalents (corresponding to 75mg / Kg effective Compound A dose), ineach rat. Details of the formulations are described in Table 10. Table 10 Particle Viscosity API size (cP)Group APIConcentration distribution Formulation composition (mg / mL) (μm) X10X50X90 1% Poloxamer 338, 0.5% 28.0 1CompoundA 300 2.0 4.1 9.5Carboxymethycellulose sodium; 3.5% MannitolComp1% Poloxamer 338, 1.5% 7.5 2oundA 300 2.1 4.511.8Polyvinylpyrrolidone; 3.5% MannitolTable 11 shows Cabotegravir plasma concentrations at different time points post-administration, and statistical analysis through t-test for plasma concentrations at each time point. The analysis indicates that for formulations dosed in groups 1 and 2, there is no significant difference in plasma concentrations over time for all time points (up to 2016hours), indicating that the PK profile is not affected in the two compositions for CompoundA. Table 11 Animal Group 1 Group (75mg / Kg SC)1Group 2 (75mg / Kg SC)1pvalu322 eTime (h) Mean SD Mean SDh ng / mL ng / mL ng / mL ng / mL G1 vs G21 18.8 5.1 BLQ N / A N / A3 34.2 16.2 23.3 13.3 0.2107 86.0 44.8 58.0 16.5 0.18312 188.0 108.6 183.3 26.7 0.47324 437.3 240.5 525.7 60.2 0.28548 1025.7 410.8 998.7 255.9 0.46472 1790.0 548.4 1703.3 65.1 0.40096 2213.3 696.4 2123.3 143.6 0.419336 5013.3 1577.0 5356.7 1197.1 0.389672 5973.3 1692.1 6010.0 1807.7 0.4901104 5460.0 1338.4 5176.7 1701.0 0.4161344 5100.0 1415.2 4783.3 1636.5 0.4062016 4393.3 880.4 4166.7 1131.4 0.3991Corresponding to 45mg / Kg CAB-equivalents.2SD: Standard Deviation.3p value calculated from one-tailed unpaired t-test for significance: * = 0.01<p<0.05; ** = 0.001<p<0.01; *** = 0.0001<p<0.001; **** = p<0.0001. Legend: ng: nanograms; BLQ: Below limit of quantitation; N / A: Not applicable.Example 7 – Comparison of intramuscular (IM) and subcutaneous (SC) administrationThis example examines outcomes from selected groups to understand impact of route of administration (Intramuscular and Subcutaneous) on PK performance ofCompound A Lyophile formulation. Lyophile formulation of Compound A was dosedsubcutaneously (SC) and intramuscularly (IM) in Sprague Dawley male rats at 75mg / Kg ofCompound A with a single bolus injection in the thigh (hindlimb) and into the rightinterscapular region, respectively. The lyophilized product was reconstituted with water for injection at 300mg / mLCompound A and administered IM or SC through a single injection at target dose of 45mg / kgof Cabotegravir equivalents (corresponding to 75mg / Kg effective Compound A dose), ineach rat. Details of the formulation are described in Table 12. Table 12 Particle size API distribution Formulation compositionGroup APIConcentration (μm) and route of (mg / mL)x10 x50 x90 administration1% Poloxamer 338, 0.5% 1Compound A 300 2.0 4.1 9.5Carboxymethycellulose sodium; 3.5% Mannitol – IM1% Poloxamer 338, 0.5% 2Compound A 300 2.0 4.1 9.5Carboxymethycellulose sodium; 3.5% Mannitol – SC Table 13 shows Cabotegravir plasma concentrations at different time points post- administration and statistical analysis through t-test for plasma concentrations at each time point. The analysis indicates that for formulations dosed in groups 1 and 2, there is no significant difference in plasma concentrations over time for all time points (up to 2016hours), indicating that the PK profile for Compound A is not impacted by the route ofadministration. Table 13 Group 1 Group 2 (75mg / Kg)#(75mg / Kg)#Time (h) Mean SD Mean SD p value48 1025.7 410.8 1317.1 120.3 0.08696 2213.3 696.4 2386.3 119.5 0.294336 5013.3 1577.0 5408.2 649.2 0.313672 5973.3 1692.1 5608.2 1085.7 0.3591104 5460.0 1338.4 4978.1 823.8 0.2721344 5100.0 1415.2 4903.8 499.6 0.3892016 4393.3 880.4 4474.2 489.8 0.4351Corresponding to 45mg / Kg CAB-equivalents2SD: Standard Deviation3p value calculated from one-tailed unpaired t-test for significance: * = 0.01<p<0.05; ** = 0.001<p<0.01; *** = 0.0001<p<0.001; **** = p<0.0001 It will be understood that the present invention has been described purely by way of example, and modification of detail can be made within the scope of the invention. Each feature disclosed in the description, and where appropriate the claims and drawings, may be provided independently or in any appropriate combination.Example 8 - Compound A Pharmacokinetics in Non-Human Primates (NHP)In this preclinical assessment, two formulations of Compound A (Table 14) weredosed subcutaneously (SC) in three Cynomolgus male NHPs per group at 40mg / Kg or at75mg / Kg of Compound A with a single bolus injection into the right dorsal lumbar region. Both lyophilized products were reconstituted with water for injection at 300mg / mL Compound A and were administered SC through a single injection at target dose of 24mg / Kg or 45mg / Kg of Cabotegravir equivalents (corresponding to 40mg / Kg or 75mg / Kgeffective Compound A dose), in each rat. Details of the formulation compositions,Compound A particle size, and in vivo study groups and doses are described in Table 14.Table 14 Compound A Particle size Dose Group Concentrationdistribution (μm) Formulation composition(mg / Kg) (mg / mL)x10 x50 x901.0% Poloxamer-338, 0.5% Sodium 1300 2.0 4.1 9.5Carboxymethylcellulose; 3.5% 40 Mannitol 1.0% Poloxamer-338, 0.5% Sodium 2300 2.0 4.1 9.5Carboxymethylcellulose; 3.5% 75 Mannitol 1.0% Poloxamer-338, 1.5% 3300 2.1 4.5 11.8Polyvinylpyrrolidone K12; 3.5% 40 Mannitol 1.0% Poloxamer-338, 1.5% 4300 2.1 4.5 11.8Polyvinylpyrrolidone K12; 3.5% 75 MannitolFigure 12 shows the pharmacokinetics time course for Cabotegravir plasmaconcentrations post-administration. Figure 4A and 4B highlight the dose-response for the Sodium Carboxymethylcellulose and for the Polyvinylpyrrolidone K12 formulations,respectively. Importantly, the PK profiles reported in figure 4 indicate a steady release ofcompound A and sustained plasma concentrations for 6 months post-injections for bothformulations and both doses, indicating potential for a twice-yearly dosing regimen.Example 9 - Pharmaceutical CompositionsTable 15 Ingredient Concentration measuredpre-lyophilization and pre- reconstitution (mg / mL) Compound A, micronized 300.0PVP K12 15.0Poloxamer 338 10.0Mannitol 35.0Citric acid monohydrate 0.75Sodium citrate dihydrate 1.75Table 15 shows an exemplary pharmaceutical composition of the invention which wasmade using the following method: Aformulation vehicle was prepared by dissolving 33.3 g Poloxamer 338 (BASF,Kolliphor P338) in about 2323 g water for injection (WFI). After P338 was fully dissolved inWFI, 49.95 g of PVP K12 (Ashland, Plasdone C-12), 116.55 g mannitol (Roquette Freres),2.50 g citric acid monohydrate (Merck Millipore) and 5.83 g sodium citrate dihydrate(Avantor or Jungbunzlauer) were added one at a time and dissolved in the solution. Thebulk vehicle was then filtered through a 0.22 μm filter. 680.7 g Compound A gammairradiated, micronized API (target X50 = 3-5μm particle size) was slowly added to 1692 g ofvehicle while stirring with vortex and may be deaerated. The suspension then continued tostir overnight. After stirring overnight, the suspension was homogenized for up to 11minutes at 15 Hz rpm and up to 109 minutes at 40 Hz. The suspension was filtered,deaerated (if needed) and filled into vials. The product was lyophilized by freezing at -45°C for 185 minutes, annealing at - 18°C for 207 minutes, refreezing at -45°C for 207 minutes (each transition at a ramp rate of+ / - 1°C / min), primary drying at -10°C (ramp rate: 0.175°C / min) for approximately 28 hoursat approximately 150 mTorr, and secondary drying at 25°C (ramp rate: 0.145°C / min) forapproximately 34 hours at approximately 150 mTorr. The lyophilized vials were backflushedwith nitrogen to about 650 Torr, sealed, and sterilized by gamma irradiation at a minimumdose of 25kGy. The formulation was reconstituted with WFI and briefly shaken to resuspendprior to administration. Table 16 Ingredient Concentration postreconstitution (mg / mL) Compound A, micronized 300Povidone 15Poloxamer 338 10Mannitol 35Citric acid monohydrate 0.75Sodium citrate dihydrate 1.75Table 16 shows a lyophilized suspension reconstituted at drug concentration of 300 mg / mL.The lyophilized cake (manufactured at 300 mg / mL above in Table 15) was reconstituted to300 mg / mL by adding 1.7 mL WFI into the vial. The vial was then reconstituted with a 10-second interval quick wrist movement. The action was repeated until the bottom of the vialwas clear, and the cake fully dispersed into a suspension. Table 17 summarizes the stabilityof composition shown in Table 15 and Table 16.Table 17 Batch 3 Conten Storage Recon. Resusp. IF Time t (% Impurity Conditi time Time XRPD PSD (μm) (25G) pH (months) Label (% Area) on (sec) (sec) (N) Claim) Initial X10: 1.9, Form 1post0 10 10X50: 4.0,4.7 95.6 1.4 5.0gamma X90: 8.2 irradiat ion X10: 1.9, 1M 10 10 Form 1X50: 4.1,4.3 98.9 1.3 5.05°C / Am X90: 8.2 bH X10: 1.9, 3M 10 10 Form 1X50: 4.1,4.3 101.1 1.5 5.0X90: 8.2 X10: 1.9, 1M 10 10 Form 1X50: 4.2,4.4 98.4 1.4 5.025 X90: 8.6 °C / 60% X10: 1.9, RH 3M 10 10 Form 1X50: 4.2,4.7 102.2 1.3 5.0X90: 8.5 Form 1, X10: 2.0, 1M 10 10<5% X50: 4.4,4.6 98.4 1.4 5.040 Group B X90: 9.3 °C / 75% Form 1, X10: 2.1, RH 3M 10 10<5% X50: 4.8,5.0 101.6 1.9 4.7Group B X90: 11.7 Table 18 Ingredient Concentration postreconstitution (mg / mL) Compound A, micronized 395Povidone 19.75Poloxamer 338 13.17Mannitol 46.07Citric acid monohydrate 0.99Sodium citrate dihydrate 2.30Table 18 shows a lyophilized suspension reconstituted at drug concentration of 395 mg / mL.The lyophilized cake (manufactured at 300 mg / mL above in Table 15) can be reconstitutedto 395 mg / mL by adding 1.2 mL WFI into the vial. The vial is then reconstituted with a 10-second interval quick wrist movement. The action is repeated until the bottom of the vial isclear, and the cake fully dispersed into a suspension. Table 19 Ingredient Concentration postreconstitution (mg / mL) Compound A, micronized 450.0Povidone 22.5Poloxamer 338 15.0Mannitol 52.5Citric acid monohydrate 1.13Sodium citrate dihydrate 2.63Table 19 shows a lyophilized suspension reconstituted at drug concentration of 450 mg / mL.The lyophilized cake (manufactured at 300 mg / mL above in Table 15) can be reconstitutedto 450 mg / mL by adding 0.9 mL WFI into the vial. The vial is then reconstituted with a 10-second interval quick wrist movement. The action is repeated until the bottom of the vial isclear, and the cake fully dispersed into a suspension.Example 10 Pharmaceutical CompositionsTable 20 Ingredient Concentration measuredpre-lyophilization and pre- reconstitution (mg / mL) Compound A, micronized 400.0Povidone 20.0Poloxamer 338 13.3Mannitol 35.0Citric acid monohydrate 0.75Sodium citrate dihydrate 1.75Table 20 shows an exemplary pharmaceutical composition of the invention which wasmade using the following method: Aformulation vehicle was prepared by dissolving 7.98 g Poloxamer 338 (BASF,Kolliphor P338) in about 364.9 g water for injection (WFI). After P338 was fully dissolvedin WFI, 12 g of Povidone (Ashland, Plasdone C-12), 21 g mannitol (Roquette Freres), 0.45g citric acid monohydrate (Merck Millipore) and 1.05 g sodium citrate dihydrate (Avantor orJungbunzlauer) were added one at a time and dissolved in the solution. The bulk vehiclewas then filtered through a 0.22 μm filter.240 g Compound A gamma irradiated, micronizedAPI (target X50 = 3-5μm particle size) was slowly added to 407.4 g of vehicle while stirringwith vortex and may be deaerated. The suspension then continued to stir overnight. Afterstirring overnight, the suspension was homogenized for up to 10 minutes at 5000 rpm andup to 80 minutes at 10000 rpm. The suspension was filtered, deaerated (if needed) andfilled into vials. The product was lyophilized by freezing at -45°C for 185 minutes, annealing at - 18°C for 207 minutes, refreezing at -45°C for 207 minutes (each transition at a ramp rate of+ / - 1°C / min), primary drying at -10°C (ramp rate: 0.175°C / min) for approximately 24 hoursat approximately 150 mTorr, and secondary drying at 25°C (ramp rate: 0.145°C / min) forapproximately 20 hours at approximately 150 mTorr. The lyophilized vials were backflushedwith nitrogen to about 650 Torr, sealed, and sterilized by gamma irradiation at a minimumdose of 25kGy. The formulation was reconstituted with WFI and briefly shaken to resuspendprior to administration. Table 21 Ingredient Concentration postreconstitution (mg / mL) Compound A, micronized 450.0Povidone 22.5Poloxamer 338 14.99Mannitol 39.4Citric acid monohydrate 0.84Sodium citrate dihydrate 1.97Table 21 shows a lyophilized suspension reconstituted at drug concentration of450 mg / mL. The lyophilized cake (manufactured at 400 mg / mL above in Table 20) can bereconstituted to higher drug concentrations by reconstituting with a smaller quantity ofWFI. To get a 450 mg / mL drug load, 1.2 mL of WFI was injected into the vial. The vial wasthen reconstituted with a 10-second interval quick wrist movement. The action wasrepeated until the bottom of the vial was clear, and the cake fully dispersed into asuspension. Table 22 Batch 4 Conten Storage Recon. Resusp. XRPD IF Impurity Time t (% Conditi time Time (% form PSD (μm) (25G) (% pH (months) Label on (sec) (sec) 1) (N) Area)1Claim) Initial post Form 1, X10: 1.9, gamma0 20 NA <5 wt%X50: 4.0,14.8 100.6 1.46 5.1irradiat Group B X90: 8.9 ionTable 22 shows stability data of the composition discussed in Table 20 and reconstitutedto 450 mg / mL (composition in Table 21).

Claims

CLAIMS pharmaceutical composition comprising Compound A, ,2. The pharmaceutical composition according to Claim 1, wherein the poloxamer is P338.

3. The pharmaceutical composition according to Claim 1 or Claim 2, wherein the weight ratio of the poloxamer to Compound A is about 1:25 to about 1:

35.

4. The pharmaceutical composition according to any preceding claim, wherein the composition further comprises mannitol.

5. The pharmaceutical composition according to Claim 4, wherein the weight ratio of mannitol to Compound A is about 1:5 to about 1:

12.

6. The pharmaceutical composition according to any previous claim, wherein the pharmaceutical composition comprises a stabilizer selected from the group consisting of sodium carboxymethylcellulose (NaCMC), polyvinylpyrrolidone (PVP), polyethylene glycol 3350 and polyethylene glycol 4000.

7. The pharmaceutical composition according to Claim 6, wherein the stabilizer is sodium carboxymethylcellulose (NaCMC).

8. The pharmaceutical composition according to Claim 7, wherein the weight ratio of NaCMC to Compound A is about 1:50 to about 1:

70.

9. The pharmaceutical composition according to Claim 6, wherein the stabilizer is polyvinylpyrrolidone (PVP).

10. The pharmaceutical composition according to Claim 9, wherein the PVP is PVP K12.

11. The pharmaceutical composition according to Claim 9 or 10, wherein the weight ratio of PVP to Compound A is about 1:15 to about 1:

25.

12. The pharmaceutical composition according to any preceding claim, wherein Compound A is present in the form of particles having a mass median size (X50) of between (and including) 1 μm and 15 μm.

13. The pharmaceutical composition according to Claim 12, wherein the particles have a mass median size (X50) of between (and including) 3 μm and 6 μm.

14. The pharmaceutical composition according to any preceding claim, wherein the pharmaceutical composition comprises a buffer comprising citric acid monohydrate and sodium citrate dihydrate.

15. The pharmaceutical composition according to any preceding claim, wherein the composition is in the form of a lyophilised powder.

16. The pharmaceutical composition according to any of Claims 1 to 15 wherein the composition is: (a) reconstituted from a lyophilized powder with water; or (b) provided as a liquid formulation.

17. The pharmaceutical composition according to any one of claims 1 to 16, wherein the pharmaceutical composition is formulated as a parenteral pharmaceutical composition.

18. A method of treating human immunodeficiency virus (HIV) infection in a human in need thereof comprising administering to said human a therapeutically effective amount of the pharmaceutical composition according to any one of Claims 1 to 17.

19. A method of preventing human immunodeficiency virus (HIV) infection in a human in need thereof comprising administering to said human an effective amount of the pharmaceutical composition according to any one of Claims 1 to 17.

20. The method according to Claim 18 or 19, wherein the pharmaceutical composition is administered to the human via an injection.

21. The method according to Claim 20, wherein the injection is administered intramuscularly (IM) or subcutaneously (SC).

22. The method according to any one of Claims 18 to 21, wherein about 300 mg to about 3000 mg of Compound A is administered to the human.

23. The method according to any one of Claims 18 to 22, wherein the method comprises administering the pharmaceutical composition to the human once every 4 to 18 months.

24. The method according to Claim 23, wherein the method comprises administering the pharmaceutical composition to the human once every 6 to 12 months.

25. The pharmaceutical composition according to any one of Claims 1 to 17, for use in therapy.

26. The pharmaceutical composition according to any one of Claims 1 to 17 for use in treatment or prevention of human immunodeficiency virus (HIV) infection.

27. The pharmaceutical composition for use according to Claim 25 or Claim 26, wherein administration of the pharmaceutical formulation is via an injection.

28. The pharmaceutical composition for use according to Claim 27, wherein the injection is administered intramuscularly (IM) or subcutaneously (SC).

29. The pharmaceutical composition for use according to any one of Claims 26 to 28, wherein 2 mL to 10 mL of the composition or the pharmaceutical composition is administered to a human.

30. The pharmaceutical composition for use according to any one of Claims 26 to 29, wherein about 300 mg to about 3000 mg of Compound A is administered to a human.

31. The pharmaceutical composition for use according to any one of Claims 26 to 30, wherein the use comprises administering the pharmaceutical composition to the human once every 4 to 18 months.

32. The pharmaceutical composition for use according to Claim 31, wherein the use comprises administering the pharmaceutical composition to the human once every 6 to 12 months.

33. Use of the pharmaceutical composition according to any one of Claims 1 to 17, in the manufacture of a medicament for treatment of human immunodeficiency virus (HIV) infection.

34. A kit comprising a container comprising the pharmaceutical composition according to any one of Claims 1 to 17 as a lyophilised powder.

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