Study of an Injectable Regimen of GS-3242 With Lenacapavir Compared to Biktarvy in People New to HIV-1 Treatment

An Operationally Seamless Phase 2/3 Randomized, Open-label, Active-Controlled Study Evaluating the Safety and Efficacy of an Injectable Regimen of GS-3242 in Combination With Lenacapavir Versus Biktarvy (Bictegravir/Emtricitabine/Tenofovir Alafenamide) in Treatment-Naive People With HIV-1

The study will have two portions: Phase 2 and Phase 3. Phase 2 will further have 2 parts: Part A and Part B.

The goal of Phase 2, Part A is to assess the effectiveness of study drugs GS-3242 plus Lenacapavir (LEN) versus Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)), in people with HIV-1 (PWH) who are new to treatment. This will be done in Treatment Groups 1, 2 and 3 at Week 35.

The goal of Phase 2, Part B is to compare the effectiveness of study drugs, GS-3242 and LEN versus B/F/TAF in Groups 4 and 3 at Week 26.

The goal of Phase 3 is to assess the long-term effectiveness of study drug GS-3242 and LEN versus B/F/TAF, at Week 52.

The primary objectives of this study are:

Phase 2, Part A: To evaluate the efficacy of intramuscular (IM) GS-3242 plus IM LEN versus B/F/TAF in treatment-naive people with HIV-1 (PWH) in Treatment Groups 1, 2, and 3 at Week 35. Phase 2, Part B: To evaluate the efficacy of IM GS-3242 plus IM LEN versus B/F/TAF in treatment-naive PWH in Treatment Groups 4 and 3 at Week 26.

Phase 3: To evaluate the efficacy of IM GS-3242 plus IM LEN versus B/F/TAF in treatment-naive PWH at Week 52.

Key Inclusion Criteria:

• HIV-1 ribonucleic acid (RNA) ≥ 500 copies/mL at screening.
• Antiretroviral (ARV) treatment-naive, except for prior use of oral daily pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) up to 1 month prior to screening.

Key Exclusion Criteria:

• Prior usage of, or exposure to LEN or GS-3242
• Prior use of any long-acting parenteral ARV therapy (ART) medications such as monoclonal antibodies or broadly neutralizing antibodies targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine.

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