Screening

This study has a screening period, a Randomized Period, an Extension Period, and a Follow‑up Period. The screening period will happen within 30 days before the first dose of study drugs. In the screening period some tests will be done to find out who can take part in this study. About 100 people with HIV-1 (PWH) who are new to treatment will take part in this study for at least 52 weeks during the Randomized Period.

Randomized Period

In the Randomized Period, 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 LEN versus 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.

• Group 1: Participants will be randomized to receive oral loading doses of GS-3242 in combination with LEN oral tablets, followed by intramuscular (IM) injections of GS-3242 and LEN for at least 52 weeks.
• Group 2: Participants will be randomized oral loading doses of GS-3242 in combination with LEN oral tablets, followed by IM injections of GS-3242 (at a different dose than Group 1) and LEN for at least 52 weeks.
• Group 3:Participants will be randomized to receive 50/200/25 mg of B/F/TAF daily for at least 52 weeks

Part B will start only if the results from ongoing studies are supportive. Part B consists of Group 4: GS-3242 plus LEN. If the sponsor decides to start Part B, Group 4: Participants will be enrolled (non-randomized) to receive oral loading doses of GS-3242 in combination with LEN oral tablets, followed IM injections of GS-3242 and LEN (at different doses than Group 1 and 2) for at least 52 weeks. 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.

Extension Period

After the Randomized Period, they will be offered the opportunity to enter an Extension Period for up to 2 years after GS‑3242 plus LEN become available in any country where the study is conducted or until the sponsor elects to discontinue the study, whichever occurs first.

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. During the optional Extension Period, all groups will get IM injections of GS‑3242 and LEN. The dose and dosing frequency will be determined after all participants complete 52 weeks of study treatment in the Randomized Period.

Those sassigned to Group 3 (B/F/TAF) in the Randomized Period who decide to take part in the optional Extension Period, will get GS‑3242 plus LEN for the first time at the End of Randomized Study Treatment visit.

Follow‑Up Period

After stopping GS‑3242 plus LEN or B/F/TAF for any reason, there will be an Early Study Drug Discontinuation visit within 3 days after the last dose of GS‑3242 plus LEN or B/F/TAF. Participants will be in the Follow‑up Period  during which the site will continue to health checks.

Those who recieved GS-3242 plus LEN, will have 4 follow-up visits until about 370 days after the last dose of study drugs. Two of these 4 follow-up visits will be a phone call to ask about health conditions and any other treatments or medications being taken.

Those who received B/F/TAF only will have 1 follow-up visit about 30 days after the last dose of study drug.

Completion

The information collected from  at each visit, including the visits during the Follow-up Period, helps us learn more about the study drug, HIV or the development of new medicines to help people with HIV in the future. Participants will be informed in a timely manner of any significant new information that may affect their willingness to continue to take part in the current study.