1. To design and conduct studies of long-acting antiretroviral (ARV) agents and delivery systems for pre-exposure prophylaxis (PrEP)
Rationale: Long-acting systemic ARV agents will facilitate adherence with PrEP, a major limitation to PrEP effectiveness.
1a. To design and conduct Phase 1 and 2 studies to evaluate the safety, acceptability and pharmacokinetic/pharmacodynamic (PK/PD) characteristics of long-acting ARV agents and novel delivery methods.
1b. To design and conduct Phase 3 studies to evaluate the safety and efficacy of novel long-acting ARV agents for HIV prevention. These may be delivered orally, by injection or infusion, or via devices such as implants or microneedle patches.
1c. To design and conduct bridging studies to evaluate the safety and acceptability of long-acting ARV agents among specific populations such as adolescents and pregnant women.
2. To design and conduct studies to evaluate multipurpose prevention technologies (MPTs) that concurrently prevent HIV and pregnancy, sexually transmitted infections (STIs) or opioid dependence.
2a. To design and conduct Phase 1 and 2 studies to evaluate the PK/PD, drug interactions and safety of MPT candidates (e.g., injectable, implants, patches, rings) for HIV and contraception, STIs or opioid dependence.
2b. To design and conduct Phase 3 studies to evaluate the safety and efficacy of an MPT for prevention of HIV and pregnancy which may be delivered by an injection, implant, microneedle patch or intravaginal ring.
2c. To design and conduct studies to determine the acceptability and adherence with a co-formulated TDF/FTC-contraceptive oral agent; as an attractive option for women seeking contraception and HIV prevention. A Phase 3 study may not be required as efficacy of each component is known.
3. To design and conduct studies in collaboration with the HIV Vaccine Trials Network to evaluate broadly neutralizing antibodies (bnAbs), alone and in combination, for PrEP
Rationale: A combination of bnAbs, if proven to be safe, effective and scalable, would be an additional option to ARV-based PrEP.
3a. To design and conduct Phase 1 and Phase 2 studies to evaluate PK/PD, safety and the ex vivo viral neutralization activity of bnAbs with different specificities and binding sites.
3b. To design and conduct Phase 3 studies of a multi-target bnAb or combinations of bnAbs to evaluate their efficacy and safety for PrEP.
4. To design and conduct integrated strategies for HIV prevention
Rationale: Effective HIV prevention requires an integrated package of interventions tailored to the needs of populations at risk
4a. To design and conduct integrated strategies studies consisting of biomedical, socio-behavioral and structural interventions appropriate for priority populations at risk for HIV.
4b. To use diverse designs for integrated strategies studies including cluster randomization, factorial, and step-wedge to evaluate the effectiveness of package and individual components for HIV prevention.
4c. To identify geographic “hotspots” and clusters of HIV transmission using HIV recency testing, HIV molecular phylogeny and phylogeography, enabling focused HIV prevention interventions.
4d. To include robust process measures to determine reasons for success or failure of integrated HIV prevention strategies.
4e. To utilize mathematical modeling of data from integrated strategy studies to estimate impact at a population level