Study of Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults With HIV-1 on Stable Oral Treatment Regimens

Key Inclusion Criteria:

• Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria:

• Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening.
• Plasma HIV-1 RNA levels < 50 copies/mL at screening.
• At least 1 documented HIV-1 RNA level measured between 6 months and 12 months (+2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be < 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). A single virologic elevation of ≥ 50 copies/mL and < 400 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable if the subsequent plasma HIV-1 RNA level is < 50 copies/mL.
• A plasma HIV-1 RNA test < 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) within the last 6 months prior.
• If > 1 plasma HIV-1 RNA measurements in the last 6 months prior to screening are available, all must be < 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
• On a stable oral antiretroviral (ARV) therapy (ART) for ≥ 6 months prior to screening.
• A change in ART regimen ≥ 3 months prior to the screening visit for reasons other than virologic failure (eg, tolerability, simplification, drug-drug interaction profile) is allowed; individuals with a change in ART regimen ≥ 3 months prior to screening must have been on the regimen for ≥ 3 months prior to screening, and all HIV-1 RNA measurements in that period must be < 50 copies/mL. There are no permitted changes to ART regimens between screening and Day 1.

Key Exclusion Criteria:

• History of an opportunistic infection or illness indicative of Stage 3 HIV disease.
• Known hypersensitivity to the study intervention, its metabolites, or formulation excipients.
• Active, serious infections (other than HIV-1) requiring therapy < 30 days prior to randomization.
• Active tuberculosis infection.
• Acute hepatitis of any cause < 30 days before randomization.
• History of, or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or severe hepatic impairment (Child-Pugh Class C).
• Active malignancy requiring acute systemic therapy.
• Have poor venous access that would limit phlebotomy or intravenous (IV) infusion of study drugs.
• Prior use of, or exposure to, LEN or a broadly neutralizing antibody (bNAb) for HIV-1.
• Prior use of, or exposure to, long-acting (LA) injectable cabotegravir (CAB) or LA injectable rilpivirine (RPV).
• Prior use of, or exposure to, ibalizumab, fostemsavir, or maraviroc.
• Current use of, or exposure to, nevirapine or zidovudine.
• Baseline regimen consisting of monotherapy with any single ARV.
• Treatment with immunosuppressant therapies (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) within 4 weeks of screening (with the exception of a single short course of corticosteroids lasting ≤ 7 days) or have a comorbid condition with an anticipated need ongoing immunosuppressive treatment during the study.
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.
• Chronic hepatitis B virus (HBV) infection, as determined by either:

• Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
• Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.

Note: Individuals found to be susceptible to HBV infection (eg, negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive an HBV vaccination. Those who remain non-immune will receive regular testing for HBV.

• Severe renal impairment-estimated glomerular filtration rate < 30 mL/min according to the Cockcroft-Gault formula.
• Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant, as determined by the investigator.
• Any of the following laboratory values at screening:

• Alanine aminotransferase > 5 × upper limit of normal (ULN).
• Direct bilirubin > 1.5 × ULN
• Platelets < 50,000/mm^3.
• Hemoglobin < 8.0 g/dL.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.