VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1

Inclusion Criteria:

• Participant must be 18 to 65 years of age inclusive at the time of signing theinformed consent.

• Participants who are overtly healthy (other than HIV infection) as determined by theInvestigator or medically qualified designee based on a medical evaluation includingmedical history, physical examination, laboratory tests, and cardiac monitoring.

• Positive HIV antibody test

• Documented HIV infection and Screening plasma HIV-1 RNA ≥ 3,000 copies/mL. A singlerepeat of this test is allowed within a single Screening period to determineeligibility.

• Screening CD4+ T-cell count ≥200 cells/mm3

• Treatment-naïve: No antiretrovirals (ARVs, in combination or monotherapy) receivedafter the diagnosis of HIV-1 infection.

• HIV Pre-exposure or post-exposure prophylaxis: No prior use of any INSTI (includingcabotegravir) for HIV pre-exposure or post-exposure prophylaxis.

• Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and BMIwithin the range 18.5-31.0 kg/m2 (inclusive - applies to males and females).

• A participant of childbearing potential must have a negative serum hCG test atscreening, and negative urine hCG test at Day 1, before the first dose of studyintervention.

• If a urine test cannot be confirmed as negative (e.g. ambiguous result), a serumpregnancy test is required. In such cases, the participant must be excluded fromparticipation if the serum pregnancy result is positive.

• The Investigator is responsible for review of medical history, menstrual history,and recent sexual activity to decrease risk for inclusion of a female with an earlyundetected pregnancy.

• Capable of giving signed informed consent

• Participant must be willing and able to start standard-of-care ART as selected withthe investigator on Study Day 10.

Exclusion Criteria:

• Participants with primary HIV infection. Any evidence of an active CDC Stage 3disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during thestudy. Untreated syphilis infection [positive RPR at screen] without documentationof treatment. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cellcarcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical,anal or penile intraepithelial neoplasia; or other localized malignancies

• Any pre-existing physical or mental condition which, in the opinion of theInvestigator, may interfere with the participant's ability to comply with the dosingschedule and/or protocol evaluations or which may compromise the safety of theparticipant.

• Any history of significant underlying psychiatric disorder, or a clinical assessmentof suicidality based on the responses on the eCSSRS.

• Any history of major depressive disorder with or without suicidal features, oranxiety disorders, that required medical intervention (pharmacologic or not) such ashospitalization or other inpatient treatment and/or chronic (>6 months) outpatienttreatment.

• Current or chronic history of liver disease or known hepatic or biliaryabnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Medical history of cardiac arrhythmias or cardiac disease or a family or personalhistory of long QT syndrome or sudden cardiac death. Treatment with immunomodulatingagents (such as systemic corticosteroids, interleukins, interferons) or any agentwith known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days ofstudy drug administration.

• Past or intended use of over-the-counter or prescription medication including herbalmedications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing. Specific medications listed inSection 6.9.1 may be allowed.

• Participants who require concomitant medications known to be associated with aprolonged QTc.

• Participants receiving any protocol-prohibited medication(s) and who are unwillingor unable to switch to an alternate medication).

• The participant has ever received an investigational HIV vaccine (immunotherapeuticor immunomodulatory).

• Exposure to an experimental drug or experimental vaccine within either 30 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 study intervention.

• Participation in the study would result in donation of blood in excess of 500 mLwithin 56 days.

• Exposure to more than four new investigational drugs or vaccines within 12 monthsprior to the first dosing day.

• Current enrollment or past participation within the last 30 days, 5 half-lives ortwice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent in any other clinical studyinvolving an investigational study intervention or any other type of medicalresearch.

Diagnostic Assessments

• Presence of HBsAg or HBcAb at screening

• Positive Hepatitis C antibody test result at Screening

• Positive Hepatitis C RNA test result at Screening.

• Creatinine clearance (eGFR) of < 60 mL/min/1.73 m2 using CKD-EPI equation (2021).