Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)

Inclusion criteria:

Type of participant

1. Participants must have recently completed or be currently enrolled and ongoing inone of the following studies on the CAB LA arm:

• HPTN 083 open label extension

• HPTN 084 open label extension (including pregnancy sub-study) Participants that completed study participation ≥3 months ago must be discussed withthe Medical Monitor prior to enrolment. Participants who have prematurely withdrawn from prior CAB PrEP studies cannotenroll into this study.

2. Evidence of continued benefit (HIV negative and at risk) from CAB LA duringparticipation in the parent study/sub-study.

3. Participants must have nonreactive HIV tests at Screening (rapid test, immunoassay [antigen/antibody] test and HIV-1 RNA results must all be available and nonreactive)and Day 1 (at least one of rapid test and immunoassay [antigen/antibody test]results must be available and nonreactive). Participants who have one or morereactive or positive HIV test result(s) will not be enrolled, even if subsequentconfirmatory testing indicates they are not HIV-infected. Sex

4. Males and Females: All participants who are engaging in sexual activity should be counselled on safersexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of acquiring HIV and other STIs. Females: Cisgender female participants who are of childbearing potential and who are engagingin sexual activity that could lead to pregnancy, must talk to the investigator aboutrecommended contraception options. Contraception will be optional in this study.Condoms are recommended in addition, because their appropriate use is the onlycontraception method effective for preventing HIV-1 transmission. Pregnant participants from the HPTN 084 study are eligible to enroll into this studyif they meet all eligibility criteria. Informed consent

5. Participant or caregiver/legal guardian is able and willing to provide signedinformed consent as described in Protocol Section 11.1.5, which includes compliancewith the requirements and restrictions listed in the consent form and in thisprotocol. Where applicable, participants must provide written assent.

Exclusion Criteria:

Concurrent conditions/medical history (includes liver function)

1. Participants who are currently enrolled in the eligible studies on the TDF/FTC armare not eligible to enroll into this study. Participants receiving short-term oralTDF/FTC bridging may be enrolled following consultation with the Medical Monitor.

2. Previous premature discontinuation from IP in the parent study/sub-study.

3. ALT >5 × ULN; or ALT>3 × ULN and bilirubin >1.5 × ULN (with >35% direct bilirubin)in the screening liver chemistry test result.

4. Participants with known active hepatitis B infection (as indicated by a positiveHBsAg and/or quantifiable HBV DNA). Participants negative for HBsAg but positive foranti-HBc and positive for anti-HBs (past and/or current evidence) are immune to HBVand are not excluded.

5. Unstable liver disease (as defined by any of the following: presence of ascites,encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, orpersistent jaundice or cirrhosis), known biliary abnormalities (with the exceptionof hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomaticgallstones or otherwise stable chronic liver disease per investigator).

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

7. Participant is currently participating in or has participated in a study (other thanthe studies listed in Inclusion Criteria 1) with a compound or device that is notcommercially available within 30 days prior to signing informed consent, unlesspermission from the Medical Monitor is granted.

8. Presence of or any history of allergy/sensitivity to the study drug or itscomponents.

9. Inflammatory skin conditions that compromise the safety of IM injections, per thediscretion of the investigator. Mild skin conditions may not be exclusionary at thediscretion of the investigator or designee.

10. Participant has a gluteal implant, tattoo or other dermatological conditionoverlying the buttock region which in the opinion of the investigator or designeemay interfere with the injection or interpretation of ISRs.results must be available and nonreactive). Participants who have one or more
reactive or positive HIV test result(s) will not be enrolled, even if subsequent
confirmatory testing indicates they are not HIV-infected.
 
Sex
 

11. Males and Females:
 
All participants who are engaging in sexual activity should be counselled on safer
sexual practices including the use and benefit/risk of effective barrier methods
 (e.g., male condom) and on the risk of acquiring HIV and other STIs.
 
Females:
 
Cisgender female participants who are of childbearing potential and who are engaging
in sexual activity that could lead to pregnancy, must talk to the investigator about
recommended contraception options. Contraception will be optional in this study.
Condoms are recommended in addition, because their appropriate use is the only
contraception method effective for preventing HIV-1 transmission.
 
Pregnant participants from the HPTN 084 study are eligible to enroll into this study
if they meet all eligibility criteria.
 
Informed consent
 

12. Participant or caregiver/legal guardian is able and willing to provide signed
informed consent as described in Protocol Section 11.1.5, which includes compliance
with the requirements and restrictions listed in the consent form and in this
protocol. Where applicable, participants must provide written assent.
 
 Exclusion Criteria:
 
 Concurrent conditions/medical history (includes liver function)
 

13. Participants who are currently enrolled in the eligible studies on the TDF/FTC arm
are not eligible to enroll into this study. Participants receiving short-term oral
TDF/FTC bridging may be enrolled following consultation with the Medical Monitor.
 

14. Previous premature discontinuation from IP in the parent study/sub-study.
 

15. ALT >5 × ULN; or ALT>3 × ULN and bilirubin >1.5 × ULN (with >35% direct bilirubin)
in the screening liver chemistry test result.
 

16. Participants with known active hepatitis B infection (as indicated by a positive
HBsAg and/or quantifiable HBV DNA). Participants negative for HBsAg but positive for
anti-HBc and positive for anti-HBs (past and/or current evidence) are immune to HBV
and are not excluded.
 

17. Unstable liver disease (as defined by any of the following: presence of ascites,
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or
persistent jaundice or cirrhosis), known biliary abnormalities (with the exception
of hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic
gallstones or otherwise stable chronic liver disease per investigator).
 

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

19. Participant is currently participating in or has participated in a study (other than
the studies listed in Inclusion Criteria 1) with a compound or device that is not
commercially available within 30 days prior to signing informed consent, unless
permission from the Medical Monitor is granted.
 

20. Presence of or any history of allergy/sensitivity to the study drug or its
components.
 

21. Inflammatory skin conditions that compromise the safety of IM injections, per the
discretion of the investigator. Mild skin conditions may not be exclusionary at the
discretion of the investigator or designee.
 

22. Participant has a gluteal implant, tattoo or other dermatological condition
overlying the buttock region which in the opinion of the investigator or designee
may interfere with the injection or interpretation of ISRs.

23. Coagulopathy (primary or iatrogenic) which would contraindicate IM injection.Concomitant medications

24. Participant is receiving any protocol-defined prohibited medication and is unwillingor unable to switch to an alternate medication.

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

26. Participant is unlikely to adhere to the study procedures, keep appointments, or isplanning to relocate during the study.

27. Any condition (i(including but not limited to substance use disorder) that would, inthe opinion of the site investigator, place the participant at an unacceptable riskof injury or render the participant unable to meet the requirements of the protocol. Other

28. 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 using appropriate HIV tests as per Inclusion Criterion

#3.

17. Participant is a ward of the state (e.g. child in care).