A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study)

Inclusion Criteria:

1. Participant must be at least 18 years of age (or older, if required for adults bylocal regulations) at the time of signing the informed consent.

2. Screening CD4+ T-cell count >200 cells/microlitre (µL).

3. Documented HIV-1 infection and Screening plasma HIV-1 RNA of ≥1000 copies/millilitre (mL). A single repeat of this test is allowed within a single Screening period todetermine eligibility.

4. Treatment-naive: Defined as no ARVs (in combination or monotherapy) received afterthe diagnosis of HIV-1 infection.

5. Body weight >=50.0 kilogram (kg) [(110 pounds (lbs)] for participants assigned maleat birth and >=45.0 kg (99 lbs) for participants assigned female at birth. BMIwithin the range 18.5-35.5 kg/m^2 (inclusive - applies to males and females).

6. There are no contraceptive requirements for participants assigned male at birth.

7. Participants assigned female at birth are eligible to participate if they are notpregnant or breastfeeding and one of the following conditions applies:

• Is a Participant of non-childbearing potential (PONCBP);OR Is a Participant ofchildbearing potential (POCBP) and using a contraceptive method with a failurerate of less than (<) 1% prior to and during the study intervention period, andfor at least 1 week after the last dose of VH4524184 plus FTC/TAF FDC, orthrough the end of study (if in the control arm and never received VH4524184).

• A POCBP must have a negative pregnancy test at Screening (serum) and on Day 1 (urine) before the first dose of study intervention.

• If a urine test cannot be confirmed as negative (e.g., an ambiguous result), aserum pregnancy test is required. Participant with a positive serum test mustbe excluded.

8. Capable of giving signed informed consent.

Exclusion Criteria:

1. Participants who are breastfeeding or plan to breastfeed during the study.

2. Participants with acute HIV infection, evidenced by acute retroviral syndrome (e.g.,fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months)documented viremia without antibody production and/or evidence of recent (within 3months) documented seroconversion.

3. Any evidence of an active Centres for Disease Control and Prevention (CDC) Stage 3disease [CDC 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapyduring the study. Historical CD4+ cell counts less than 200 cells/µL are notexclusionary.

4. Unstable liver disease known biliary abnormalities (with the exception of Gilbert'ssyndrome or asymptomatic gallstones or otherwise stable chronic liver disease perinvestigator assessment).

5. History of cirrhosis with or without viral hepatitis co-infection.

6. Participants with HCV co-infection will be excluded from the study.

7. Individuals who are co-infected with HIV and HBV will be excluded Participantsdiagnosed with syphilis at Screening (i.e., positive syphilis testing) should betreated as per local guidelines and will be eligible to enroll at any timeregardless of the stage of disease.

8. Uncontrolled malignancy is excluded, whereas participants who have controlledmalignancies may be included in agreement between the investigator and the ViiVHealthcare medical monitor.

9. Any pre-existing physical, or mental condition (including alcohol or drug abuse)which, in the opinion of the investigator (with or without psychiatric evaluation)or the ViiV Healthcare medical monitor, may interfere with the participant's abilityto comply with the dosing schedule and/or protocol evaluations or which maycompromise the safety of the participant.

10. Any condition which, in the opinion of the investigator or the ViiV Healthcaremedical monitor, that may interfere with the absorption, distribution, metabolism orexcretion of the study interventions or render the participant unable to take oralmedication and normal gastrointestinal anatomy or motility or hepatic and/or renalfunction

11. Clinically significant CV disease, as defined by history/evidence of congestiveheart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypassgrafting surgery or percutaneous transluminal coronary angioplasty or any clinicallysignificant cardiac disease.

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

13. History of sensitivity to any of the study medications, or their components or drugsof their class, or a history of drug or other allergy that, in the opinion of theinvestigator or ViiV Healthcare medical monitor, contraindicates theirparticipation.

14. Current or anticipated need for chronic anti-coagulation with the exception of theuse of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation andplatelet disorders such as hemophilia or Von Willebrand Disease.

15. Treatment with any of the following agents within 60 days of Screening: radiationtherapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.

16. Treatment with immunomodulating agents (such as systemic corticosteroids,interleukins, interferons) or any agent with known anti-HIV activity (such ashydroxyurea or foscarnet) within 30 days of Day 1.

17. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

18. Exposure to an approved vaccine within 14 days prior to Day 1.

19. Current enrollment or past participation within the last 30 days before signing ofconsent in any other clinical study involving an investigational study interventionor any other type of medical research

20. Participants with known or suspected presence of virologic resistance mutations asdefined by the Stanford HIV Drug Resistance Database to INSTIs or NRTIs. Thisdetermination will be based on local virologic resistance testing, either atScreening or within the 3 months prior to Screening. ViiV Healthcare clinicalvirologist and/or ViiV Healthcare medical monitor will verify eligibility to thiscriterion prior to Day 1.

21. Creatinine clearance (eGFR) of <60 mL/min/1.73 m2 via CKD-EPI race neutral method [Delgado, 2021].

22. ALT >3 times the upper limit of normal (ULN). A single repeat of ALT is allowedwithin a single screening period to determine eligibility.

23. Any Grade 4 laboratory abnormality at screening, except for a Grade 4 CPK and lipidabnormalities (e.g., total cholesterol, triglycerides, etc.) will exclude aparticipant from the study unless the investigator can provide a compellingexplanation for the laboratory result(s) and has the assent of the ViiV Healthcaremedical monitor. A single repeat of any lab abnormality is allowed within a singlescreening period to determine eligibility.

24. Any acute laboratory abnormality at screening which, in the opinion of theinvestigator, should preclude participation in the study of an investigationalcompound.

25. Exclusion criteria for screening ECG (a single repeat is allowed for eligibilitydetermination and will be the screening ECG entered into the eCRF): QT intervalcorrected for heart rate according to Fridericia's formula (QTcF) >450 msec (males)or >470 msec (females); >480 msec for participants with bundle branch block.