Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy

History of an opportunistic infection or illness indicative of Stage 3 HIV disease.

History of treatment failure.

Known or suspected resistance to either CAB or RPV.

1. Resistance to CAB defined as the following mutations: G118R, Q148K, Q148R, T66K+L74M, E92Q+N155H, E138A+Q148R, E138K+Q148K/R, G140C+Q148R, G140S+Q148H/K/R, Y143H+N155H, and Q148R+N155H.

2. Resistance to RPV defined as the following mutations: K101E and P; E138A, G, K, R, and Q; V179L; Y181C, I, and V; Y188L; H221Y; F227C; M230I and L, and the combination of L100I/K103N.

Individuals with a dermatologic condition or implanted prothesis overlying the gluteal injection site for CAB + RPV.

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 CAB or LA injectable RPV.

Prior use of, or exposure to, ibalizumab, fostemsavir, or maraviroc.

Baseline regimen consisting of monotherapy with any single antiretroviral (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:

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

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

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:

1. Alanine aminotransferase \> 5 x upper limit of normal (ULN).

2. Direct bilirubin \> 1.5 x ULN.

3. Platelets \< 50,000/mm\^3.

4. Hemoglobin \< 8.0 g/dL.

What this study is about