Guidance for 2019 HPTN RFA CRS/CTU Applicants

HPTN Clinical Research Agenda Specific Aims
Sep 23, 2019

The specific aims proposed in the scope of work in response to the RFA for the HIV Prevention Clinical Trials Network are being posted here. The intent of this posting is to be transparent and allow all new and recompeting clinical trial sites access to the specific aims of the proposed scientific agenda for the HPTN. The content addresses the request from investigators interested in submitting CTU/CRS applications in the HIV prevention arena. This information will be removed post the submission date of the CTU application.

The goal of the HIV Prevention Trials Network (HPTN) is to reduce HIV incidence worldwide. We aim to identify novel effective, safe, acceptable, and scalable HIV prevention tools and integrated strategies, informed by biomedical and socio-behavioral research. The HPTN will collaborate with a broad range of partners including clinical research sites, community members, other DAIDS Networks, NIH Institutes and Centers, other governmental agencies, foundations, and pharmaceutical companies to achieve the following Specific Aims:

Specific Aim 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.

 

Specific Aim 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

Rationale: HIV prevention products are likely to achieve greater and more durable coverage with more significant health impact if they have a broader prevention profile for specific populations.

  • 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.

 

Specific Aim 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.

 

Specific Aim 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 modelling of data from integrated strategy studies to estimate impact at a population level.