Study of Lenacapavir Taken Twice a Year for HIV Pre-Exposure Prophylaxis (PrEP)

The goals of this clinical study are to learn more about the study drug lenacapavir (LEN), by comparing the consistent and continuous use of LEN and emtricitabine/tenofovir disoproxil fumarate (coformulated; Truvada®) (F/TDF), then by observing the safety of LEN and F/TDF, evaluating the acceptability of LEN injections and oral F/TDF, and observe how LEN moves throughout the body in people who would benefit from pre-exposure prophylaxis (PrEP).

The primary objective of this study is to compare LEN and F/TDF consistent and continuous use among people who would benefit from PrEP.


Eligibility Criteria:
Key Inclusion Criteria:

* Able to comprehend and provide a signed written informed consent, which must be obtained prior to initiation of study procedures.
* Cisgender men who have sex with men, transgender women, transgender men, cisgender women, and nonbinary people.
* Increased likelihood of HIV acquisition as indicated by at least one of the following:

  1. Condomless sex with ≥ 2 partners in the past 6 months
  2. Diagnosis of a bacterial sexually transmitted infection (STI) in the past 12 months
  3. Engagement in sex work or transactional sex in the past 12 months
  4. Use of ≥ 2 courses of nonoccupational HIV post-exposure prophylaxis (nPEP) in the past 12 months
  5. Condomless sex with a partner living with HIV who has unknown or unsuppressed viral load (≥ 200 copies/mL) in the past 12 months
* Negative local rapid HIV-1/2 antibody (Ab)/antigen (Ag) test, central HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT) at screening.

  1) If rapid HIV-1/2 Ab/Ag tests are unavailable due to extenuating circumstances, sites may run a laboratory-instrumented HIV-1/2 Ab/Ag test at their local laboratory, only if they confirm this is a fourth-generation assay and the time from blood draw to injection at any injection visit is \< 48 hours.
* Estimated glomerular filtration rate (GFR) at least 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr):

  * (140 - age in years) × (weight in kg) x (0.85 if female) = CLcr (mL/min) / 72 × (serum creatinine in mg/dL)

Key Exclusion Criteria:

* Coenrollment in any other clinical study (including observational) without prior approval from the sponsor is prohibited while participating in this study.
* Known hypersensitivity to the study drug, the metabolites, or formulation excipient.
* Current use of PrEP, defined as the use of PrEP in the preceding 4 weeks. PrEP should not be discontinued to facilitate study participation. For cabotegravir, this is defined as 4 weeks since the next injection was due (ie, 12 weeks since their most recent cabotegravir injection).
* Current use of nPEP, unless the prescribed course will be completed prior to randomization.
* Past or current participation in HIV vaccine or HIV broadly neutralizing Ab study unless participant provides documentation of receipt of placebo (ie, not active product).
* 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 (eg, ascites, encephalopathy, variceal bleeding).
* Have a suspected or known active, serious infection(s) (eg, active tuberculosis, etc).

Note: Other protocol defined Inclusion/Exclusion criteria may apply