This is a randomized, double-blinded, placebo-controlled phase 2b clinical trial to characterize, examine and compare the effects of GLP-1 receptor agonist (semaglutide) in HIV-infected adult individuals with lipohypertrophy versus healthy controls with obesity but without HIV.

The two populations will be studied in separate but similarly-designed studies running in parallel.

Subjects in both populations will be assigned by chance (1:1) to semaglutide or placebo.

Both withdrawal symptoms and external stressors can contribute to relapse in people that are trying to quit using marijuana. These negative feelings may be more severe in people that also have Major Depressive Disorder, making it especially hard for them to quit. The purpose of this study is to examine differences in withdrawal symptoms and stress response in people with Cannabis Use Disorder that do or do not also have major depression. Study participation will involve 3 on-site laboratory visits over 6 days. Participants will be asked to not use marijuana for 3 of those days. Participants will complete mobile phone surveys multiple times each day, wear a watch to assess sleep quality, and provide blood samples for testing at each laboratory visit. At the final laboratory visit, participants will complete a stress task.

This study is for Cisgender Men (CGM), Transgender Women (TGW), Transgender Men (TGM) & Gender Non-binary people (GNB) who have sex with male partners and who are at risk for HIV infection.

The study will test the experimental drug Lenacapavir (LEN) for the prevention of HIV infection, also known as Pre-Exposure Prophylaxis (PrEP). This study will also compare the effectiveness of LEN to Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF; Truvada®), which has already been approved in several countries for use as PrEP.