A Study to Investigate the Virologic Efficacy and Safety of VH3810109 + Cabotegravir Compared to Standard of Care (SOC) in Male and Female Adults Living With Human Immunodeficiency Virus (HIV)

Inclusion criteria

Age

1. Participant must be 18 to 70 years of age inclusive, at the time of signing theinformed consent. Type of Participant and Disease Characteristics

2. Must be on uninterrupted current regimen for at least 6 months prior to Screening.Any prior switch, defined as a change of a single drug or multiple drugssimultaneously, must have occurred due to tolerability/safety, access tomedications, or convenience/simplification, and must NOT have been done fortreatment failure (HIV-1 RNA ≥200 c/mL). Acceptable stable - ARV regimens prior to Screening include at least one NRTI plus:

• INI

• NNRTI

• Boosted PI (or atazanavir [ATV] unboosted)

• Excludes current use of cabotegravir or fostemsavir The addition, removal, or switch of a drug(s) that has been used to treat HIV basedon antiretroviral properties of the drug constitutes a change in ART with thefollowing limited exceptions:

• Historical changes in formulations of ART drugs or booster drugs will notconstitute a change in ART regimen if the data support similar exposures andefficacy, and the change must have been at least 3 months prior to Screening.

• Historical maternal perinatal use of an NRTI when given in addition to anongoing HAART will not be considered a change in ART regimen.

• A change in dosing scheme of the same drug from twice daily to once daily willnot be considered a change in ART regimen if data support similar exposures andefficacy.

3. Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12months prior to Screening: one within the 6 to 12-month window, and one within 6months prior to Screening;

4. Plasma HIV-1 RNA <50 c/mL at Screening;

5. Screening CD4+ T-cell count ≥350 cells/mm3: Weight

6. Body weight >=50 kg to <=115 kg. Sex

7. Male and/or female Contraceptive use by men or women should be consistent with localregulations regarding the methods of contraception for those participating inclinical studies, assuring minimal contraception requirements noted below.

All participants participating in the study 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 HIV transmission to an uninfected partner.

1. Participants who are female at birth are eligible to participate if at least one ofthe following conditions applies:

• Not pregnant or breastfeeding and at least one of the following conditionsapplies:

• Is not a participant of childbearing potential (POCBP). OR

• Is a POCBP and using an acceptable contraceptive method during theintervention period (at a minimum until after the last dose of studyintervention). The investigator should evaluate the effectiveness of thecontraceptive method in relationship to the first dose of studyintervention.

• A POCBP must have a negative highly sensitive pregnancy test (urine or serum asrequired by local regulations) on Day 1, prior to the first dose of studyintervention.

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

• The investigator is responsible for review of medical history, menstrualhistory, and recent sexual activity to decrease the risk for inclusion of aPOCBP with an early undetected pregnancy. QTc 8. QTc Interval <450 msec. Phenotypic Sensitivity 9. Viral phenotypic sensitivity to VH3810109 based on IC90 of <=2 ug/mL and a Maximum Percent Inhibition >98% using the Monogram PhenoSense mAbAssay on sample obtained at a screening visit. Informed Consent 10. Capable of giving signed informed consent which includescompliance with the requirements and restrictions listed in the informed consentform (ICF) and in this protocol.

Exclusion Criteria: Medical conditions:

• Participants who are pregnant, breastfeeding, plan to become pregnant orbreastfeed during the study

• Participants having skin disease or disorder (i.e. infection, inflammation,dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy,urticaria) or tattoo overlying potential injection sites which may interferewith interpretation of injection site reactions or administration of VH3810109or CAB

• Participant has a gluteal implant/enhancement (including fillers) overlying thegluteus area or any other area which may significantly interfere withinterpretation of injection site reactions

• Participants with known history of cirrhosis with or without viral hepatitisco-infection

• Participants with ongoing or clinically relevant pancreatitis

• Untreated syphilis infection (positive rapid plasma reagin (RPR) at screening)without documentation of treatment. Participants who are at least 7 days postcompleted treatment are eligible if recruitment is open

• Prior receipt of licensed or investigational HIV monoclonal antibody

• Any evidence of an active Centers for Disease Control and Prevention (CDC)Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemictherapy. Historical or current CD4 cell counts less than 200 cells/mm^3 are notexclusionary

• History of sensitivity to any of the study medications or their components ordrugs of their class, or a history of drug or other allergy that, in theopinion of the investigator or Medical Monitor, contraindicates theirparticipation

• Any condition which, in the opinion of the investigator, may interfere with theabsorption, distribution, metabolism or excretion of the study drugs, cART orrender the participant unable to take oral medication

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

• Previous exposure to cabotegravir

• Participant enrolled in a prior or concurrent clinical study that includes adrug intervention within the last 30 days

• Participants with ongoing chronic hepatitis B virus infection

• Participants with hepatitis C co-infection

• Participants who in the investigator's judgment, pose a significant suicidalityrisk

• Contraindications, as per the current Prescribing Information for cabotegravir.

• Previous hypersensitivity reaction to cabotegravir or

• Contraindicated co-administered drugs:

• Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin

• Antimycobacterials: Rifabutin, rifampin, rifapentine

• Glucocorticoid (systemic): Dexamethasone (more than a single-dosetreatment)

• Herbal product: St John's wort (Hypericum perforatum) Prior/Concomitant Therapy:

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

• Previous exposure to cabotegravir.

• Treatment with any of the following agents within 60 days of screening: -radiation therapy; -cytotoxic chemotherapeutic agents; -any systemic immune suppressant.

• Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half lives of the test agent, or twice the duration of the biological effectof the test agent, whichever is longer, prior to the first dose of studymedication.

• Current or anticipated need for chronic anti-coagulants.

• Participants receiving any prohibited medication and who are unwilling orunable to switch to an alternate medication. Prior/Concurrent Clinical Study Experience • Participant enrolled in a prior orconcurrent clinical study that includes a drug intervention within the last 30 days. Diagnostic Assessments

• Any acute laboratory abnormality at Screening, which, in the opinion of theinvestigator, would preclude the participants inclusion in the study of aninvestigational compound.

• Any evidence of viral resistance based on the presence of any major cabotegravirresistance-associated mutation [IAS-USA, 2022] in any historic resistance testresult.

• Any verified Grade 4 laboratory abnormality with the exception of Grade 4triglycerides or lipid abnormalities. A single repeat test is allowed during theScreening period to verify a result.

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

• Creatinine clearance of <50 mL/min/1.73 m^2 via using the refitted,race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R)method.

• PT >=Grade 2 (>=1.25 ULN). A single repeat test is allowed during the Screeningperiod to verify a result. Other Exclusion Criteria

• To assess any potential impact on participant eligibility with regard to safety,the investigator must refer to the IB and supplements, approved product labels,and/or local prescribing information for detailed information regarding warnings,precautions, contraindications, AEs, drug interactions, and other significant datapertaining to the study drugs.