The study will be conducted in 2 parts: a cross-sectional study (Incidence Phase) and a double-blind, randomized study (Randomized Phase). The Incidence Phase will include initial assessments that will provide an estimate of the concurrent background HIV-1 incidence rate. The Randomized Phase of the study will have a Blinded Phase, a LEN Open-label Extension (OLE) Phase, and a pharmacokinetic (PK) Tail Phase.
The primary objective for the Incidence Phase of this study is to estimate the HIV-1 background incidence rate. The primary objective of the Randomized Blinded Phase of this study is to evaluate the efficacy of lenacapavir for HIV-1 pre-exposure prophylaxis (PrEP) in cisgender men (CGM), transgender women (TGW), transgender men (TGM), and gender non-binary people (GNB) ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV-1 infection.
CGM, TGW, TGM, and GNB who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV infection.
HIV-1 status unknown at screening and no prior HIV-1 testing within the last 3 months
Sexually active with ≥ 1 partner assigned male at birth (condomless receptive anal sex) in the last 12 months and 1 of the following:
Condomless receptive anal sex with ≥ 2 partners in the last 12 weeks
History of syphilis, rectal gonorrhea, or rectal chlamydia in the last 24 weeks
Self-reported use of stimulants with sex in the last 12 weeks
Negative local rapid fourth generation HIV-1/2 Ab/Ag, central fourth generation HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT)
Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr)
Key Exclusion Criteria:
Prior use of oral PrEP (including F/TDF or F/TAF) in the past 12 weeks or any prior use of long-acting systemic PrEP (including cabotegravir or islatravir)
Prior recipient of an HIV vaccine or HIV broadly neutralizing antibody formulation
Acute viral hepatitis A, B or C or evidence of chronic hepatitis B or C infection
Severe hepatic impairment or a history of or current clinical decompensated liver cirrhosis
Note: Other protocol defined Inclusion/Exclusion criteria may apply.