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:

1. One HIV-1 RNA < 50 copies/mL immediately preceding the 24 weeks period prior toscreening.

2. Within 24 weeks prior to screening, if HIV-1 RNA results are available, alllevels must be < 50 copies/mL.

3. During the 6 to 12 months period prior to screening, transient detectableviremia ≥ 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 InternationalAntiviral Society (IAS), Department of Health and Human Services (DHHS), EuropeanAIDS Clinical Society (EACS) consisting of 2 or 3 ARVs for ≥ 6 months prior toscreening and willing to continue until Day 1. Individuals in Treatment Group 2 mustalso be willing to continue their standard of care through at least Week 96.

• Individuals assigned female at birth and of childbearing potential who engage inheterosexual intercourse must agree to use protocol-specified methods ofcontraception.

Key Exclusion Criteria:

• Prior virologic failure.

• Prior use of, or exposure to, ISL or LEN.

• Active, serious infections requiring parenteral therapy within 30 days beforerandomization.

• Active tuberculosis infection.

• Acute hepatitis within 30 days before randomization.

• Hepatitis B virus (HBV) infection, as determined below at the screening visit:

1. positive HBV surface antigen OR

2. positive HBV core antibody and negative HBV surface antibody. Note: individualsfound to be susceptible to HBV infection (eg negative hepatitis B surfaceantibody 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) maybe enrolled.

• Any of the following laboratory values at screening:

1. Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gaultformula

2. Alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)

3. Direct bilirubin > 1.5 x ULN

4. Platelets < 50,000/μL

5. Hemoglobin < 8.0 g/dL

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