A Study to Investigate the Use of VH3810109 With or Without Fostemsavir (FTR) to Reduce the Size and Activity of the Viral Reservoir in People Living With HIV

This study investigates the use of VH3810109 with or without FTR to reduce the size and activity of the HIV viral reservoir in two sub-populations of people living with HIV: treatment-naïve adults (Population 1) and treatment-experienced adults currently taking a standard of care (SOC) integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen (Population 2). The study is designed to include the following phases: Randomized Intervention Phase (Step 1), Analytical Treatment Interruption (ATI) Phase (Step 2), and Follow-up Phase (Step 3).

Inclusion Criteria: AGE • Age between 18 years and 70 years old at the time of obtaining informed consent. SEX AND GENDER • Persons of any sex or gender are eligible. Note: Participants of childbearing potential (POCBP) are eligible to participate if not pregnant, not lactating, and agreeing to adhere to study requirements for use of contraception and pregnancy avoidance. PARTICIPANT KEY CHARACTERISTICS • Participant has a documented diagnosis of HIV-1 infection. Note: Participants in Population 1 must have a documented positive HIV antibody result available for Screening. Population 1 only: * Plasma HIV-1 RNA \>=2000 copies/milliliter (c/mL) at Screening. * CD4+ T cell count \>=300 cells/microliter (μL) at Screening. * Antiretroviral treatment naïve, defined as no exposure to ART after a diagnosis of HIV-1 infection, prior to enrollment. Population 2 only: * Participant is stably virologically suppressed (plasma HIV-1 RNA \=450 cells/μL at Screening. WEIGHT • Body weight \>=50 kg to \=50 c/mL in the 18 months prior to Screening. INFECTIOUS DISEASES * Active hepatitis B virus (HBV) co-infection. * Active hepatitis C virus (HCV) co-infection. * Participant has untreated syphilis before enrolment. * Known history of active Mycobacterium TB disease (regardless of treatment status). ANTIRETROVIRAL RESISTANCE • Known major resistance-associated mutations to second-generation INSTIs or to antiretroviral (ARV) agents from 2 or more drug classes. PRIOR AND CONCOMITANT MEDICATIONS * Prior use of any of the following agents: \- long-acting ARVs (any dose in the past 24 months or within 5 half-lives \[whichever is longer\]) \- FTR (any lifetime use) \- HIV-1 immunotherapeutic vaccines or prophylactic vaccines (any lifetime use) \- HIV-1 monoclonal antibody therapy (any lifetime use). * Prior receipt of any approved or experimental non-HIV vaccination within 2 weeks prior to study enrolment. * History of systemic corticosteroids, immunosuppressive anti-cancer, interleukins, systemic interferons, or systemic chemotherapy, within 6 months prior to Screening. * Participant has received an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent (whichever is longer), prior to enrolment. * Treatment with any of the following agents within 30 days of enrolment: \- radiation therapy * cytotoxic chemotherapeutic agents * anti-tuberculosis therapy * immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons. * Participant is receiving any protocol-defined prohibited medication and is unwilling or unable to switch to an alternate medication. Prohibited medications must be stopped within 7 days (or 14 days if the drug is a potential CYP3A4 enzyme inducer) or 5 half-lives (whichever is longer), prior to enrolment. Population 1 only: • Known use of PrEP or PEP within \=52 weeks after the last dose of LA PrEP) are not excluded. Population 2 only: • Current use of NNRTI-containing ART. OTHER EXCLUSIONS * History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that contraindicates study participation. * Any condition which may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study drugs. * Any pre-existing physical or mental condition (including substance use disorder) which, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant. * Participant is currently participating in, or anticipates being selected for, any other interventional study. * Participant is known or suspected to be an HIV long-term non-progressor or elite controller, based on historical off-treatment plasma HIV-1 RNA results.