Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1

Key Inclusion Criteria:

• HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by:

• One HIV-1 RNA < 50 copies/mL immediately preceding the 24 weeks period prior to screening.
• Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL.
• During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable ("blip") as long as it is not confirmed on 2 consecutive visits.
• Plasma HIV-1 RNA levels < 50 copies/mL at screening.
• Are receiving guideline-recommended standard of care treatment such as International Antiviral Society (IAS), Department of Health and Human Services (DHHS), European AIDS Clinical Society (EACS) consisting of 2 or 3 ARVs for ≥ 6 months prior to screening and willing to continue until Day 1. Individuals in Treatment Group 2 must also be willing to continue their standard of care through at least Week 96.
• Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.

Key Exclusion Criteria:

• Prior virologic failure.
• Prior use of, or exposure to, ISL or LEN.
• Active, serious infections requiring parenteral therapy within 30 days before randomization.
• Active tuberculosis infection.
• Acute hepatitis within 30 days before randomization.
• Hepatitis B virus (HBV) infection, as determined below at the screening visit:

• positive HBV surface antigen OR
• positive HBV core antibody and negative HBV surface antibody. 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 HBV vaccination.
• Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: individuals with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.
• Any of the following laboratory values at screening:

• Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
• Alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)
• Direct bilirubin > 1.5 x ULN
• Platelets < 50,000/μL
• Hemoglobin < 8.0 g/dL

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