A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a New Formulation of Cabotegravir Long-Acting Administered Intramuscularly in a 4-month Dosing Interval (Q4M)

Inclusion Criteria:

1. At the time of obtaining informed consent, adolescent and adult participantsweighing at least 35 kg.

2. Participants must have a nonreactive HIV test at Screening (rapid test, nonrapid HIVimmunoassay, and HIV RNA) and enrollment (a rapid test, nonrapid HIV immunoassay,and HIV RNA).

3. Participants who are at risk of acquiring HIV, defined as having had anal or vaginalsex in the past 6 months.

4. Participants who are overtly healthy as determined by medical evaluation by aresponsible and experienced physician, including medical history, physicalexamination, laboratory tests and cardiac monitoring at the time of screening.

5. No alcohol or substance use that, in the opinion of the study investigator andmedical monitor, would interfere with the conduct of the study (e.g., provided byself-report, or found upon medical history and examination or in available medicalrecords).

6. Participants who have received oral PrEP are eligible, but they must discontinueoral PrEP within 10 days of Day 1 visit.

7. Male or female at birth, (transgender individuals are not excluded). Contraceptiveuse should align with local regulations. Participants assigned female at birth mustnot be pregnant or breastfeeding and must either not be of childbearing potential (POCBP) or use highly effective contraception. A POCBP must have a negativepregnancy test within 30 days before dosing.

8. Participants must be >=16 years old, of legal age to consent to sexual intercourse,and capable of giving written informed consent. Adolescents must provide writteninformed assent/consent and/or obtain parental/guardian consent if not of legal age,as per site SOPs and IRB/EC policies.

Exclusion Criteria:

1. One or more reactive or positive HIV test results at Screening or Enrollment, evenif HIV infection was not confirmed.

2. Participants who are breastfeeding or plan to become pregnant or breastfeed duringthe study.

3. Alanine aminotransferase (ALT) >=3 times the upper limit of normal (ULN).

4. Evidence of active Hepatitis B virus (HBV) infection.

• Participants positive for HBsAg or HBV DNA are excluded.

• Participants negative for anti-HBs but positive for anti-HBc (negative HBsAgstatus) and positive for HBV DNA are excluded.

5. Unstable liver disease, known biliary abnormalities (with the exception of Gilbert'ssyndrome or asymptomatic gallstones).

6. History of clinically relevant hepatitis within last 6 months.

7. Known history of liver cirrhosis with or without viral hepatitis co-infection.

8. Participants with Hepatitis C virus (HCV) co-infection will be allowed entry intothis study if:

• Liver enzymes meet entry criteria.

• HCV Disease has undergone appropriate work-up, and is not advanced, and willnot require treatment prior to the primary endpoint (e.g., Month 13).

• In the event that recent biopsy or imaging data is not available orinconclusive, the Fibrosis 4 (Fib-4) score will be used to verify eligibility: i. Fib-4 score greater than (>) 3.25 is exclusionary. ii. Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation. Fibrosis 4 score Formula: (Age xAST) / (Platelets x (sqr [ ALT]) It is approved by the Medical Monitor.

9. Creatinine clearance of <30 mL/min/1.73 m2 via CKD-EPIcr_R (2021) method.

10. Any acute laboratory abnormality at Screening, which, in the opinion of theinvestigator, would preclude the participant's participation in the study of aninvestigational compound.

11. Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 [triglycerides or lipid abnormalities].

12. Participants determined by the Investigator to have a high risk of seizures, Aparticipant with a prior history of seizure may be considered for enrolment if theInvestigator believes the risk of seizure recurrence is low. All cases of priorseizure history should be discussed with the Medical Monitor prior to enrolment.

13. Participant is currently participating in or has participated in a study with acompound or device that is not commercially available within 30 days of signinginformed consent, unless permission from the Medical Monitor is granted.

14. Presence of any history of allergy/sensitivity to any of the study drug.

15. Inflammatory skin conditions that compromise the safety of IM injections, per thediscretion of the investigator.

16. Participant has an implant/enhancement (including fillers) at the area of proposedinjection (e.g., gluteus medius); or tattoo or other dermatological conditionoverlying the area for IM (e.g., gluteus medius) or any other area which maysignificantly interfere with interpretation of injection site reactions.

17. Current or anticipated need for chronic anti-coagulants or active coagulopathy (primary or iatrogenic) which would contraindicate IM injection.

18. Ongoing or clinically relevant pancreatitis.

19. Clinically significant cardiovascular disease or history of clinically significantcardiovascular disease.

20. All participants will be screened for STIs (e.g., chlamydia, gonorrhea,trichomoniasis, syphilis). Participants with untreated infections are excluded.Participants may be rescreened at least 24 hours after completion of STI treatment.

21. History or presence of sensitivity to any of the study medications or theircomponents or drugs of their class, or a history of drug or other allergy that, inthe opinion of the investigator or Medical Monitor, contraindicates theirparticipation. In addition, if heparin is used during PK sampling, subjects with ahistory of sensitivity to heparin or heparin-induced thrombocytopenia should not beenrolled.

22. Ongoing uncontrolled malignancy is excluded, whereas participants who havecontrolled localized malignancies may be included on agreement between theinvestigator and the Medical Monitor.

23. Participants who in the investigator's judgment, poses a significant suicidality risk.

24. Any pre-existing physical or mental condition (including substance abuse disorder)which, in the opinion of the Investigator or the medical monitor, may interfere withthe participant's ability to comply with the dosing schedule and/or protocolevaluations or which may compromise the safety of the participant.

25. Any condition which, in the opinion of the Investigator or the medical monitor, mayinterfere with the absorption, distribution, metabolism or excretion of the studydrugs or render the participant unable to receive IM medication.

26. Co-enrollment in any other interventional research study or other concurrent studieswhich may have interfered with this study (as provided by self-report or otheravailable documentation). Exceptions for non-interventional studies may be made ifappropriate after consultation with the Medical Monitor.

27. Participants receiving any protocol-prohibited medication and who are unwilling orunable to switch to an alternate medication.

28. Use of antiretroviral therapy (ART) for Postexposure Prophylaxis within the 90 daysprior to Day 1.

29. Use of CAB LA for PrEP at any time prior to Screening.

30. Exposure to an experimental drug or experimental vaccine within either 28 days, 5half-lives of the test agent, or twice the duration of the biological effect of thetest agent, whichever is longer, prior to the first dose of IP.

31. Anticipated need for HCV therapy with interferon or any drugs that have potentialfor adverse drug:drug interactions with study treatment throughout the entire studyperiod.

32. Treatment with an HIV-1 preventive vaccine within 90 days of Screening.

33. Participant is unlikely to adhere to the study procedures, keep appointments, isplanning to relocate during the study, or remain on study through to its conclusion.

34. Participants who are considered high-risk, meeting at least one of the followingcriteria:

• Participant who has exchanged condomless sex for goods or money within the past 12 months prior to Screening.

• Participant who has used recreational intravenous drugs within the past 12months prior to Screening.

• Participant who has participated in Chemsex practice (such as the use ofcocaine, crack cocaine, methamphetamine, ketamine, 3,4-methlenedioxy-methamphetamine, GHB, mephedrone or prescription drugs apartfrom those prescribed by a licensed provider) within the past 6 months prior toScreening.

• Participant with any STI in the last 6 months also reporting any partners forcondomless sex.

• Participant who has condomless sex with a serodiscordant partner who has adetectable viral load or is not on ART.

• Participant with any other behavior assessed by the investigator as high-risksexual behavior.

35. Participant has in the last 14 days prior to Screening presented with signs andsymptoms, which, in the opinion of the investigator, are suggestive of acute HIVinfection. Participants may only be enrolled if clinical suspicion of HIV is ruledout with non-reactive results.

36. Participant becomes a ward of state (e.g., child in care).