Challenges of HIV therapeutic vaccines clinical trials design.

Purpose of the review: To discuss main challenges of therapeutic vaccine clinical trials design, implementation and analyses in the HIV cure field.

Recent findings: Therapeutic vaccines are progressively being postulated as T-cell stimulating agents to use in combination HIV cure strategies, with the addition of immunomodulators, latency reversing agents and/or broadly neutralizing antibodies. Although promising strategies are rapidly evolving in preclinical studies using nonhuman primate models, translation into human testing in randomized controlled clinical trials is more challenging and expensive to conduct. Adaptive designs, access to cohorts of early-treated individuals, consensus on how to safely conduct analytical treatment interruptions, use of alternative statistical methods, development of point-of-care/home-based testing technologies and ensuring early engagement of communities where research is being developed are some of the critical aspects to consider to facilitate clinical trial development in the HIV cure field.

Summary: Design and development of HIV therapeutic vaccine clinical trials poses many challenges, from Phase 0/pilot studies to Phase I/II trials in which efficacy of the intervention is being tested and antiretroviral therapy cessation is needed, complexity of cure trials progressively increases. Understanding fundamental issues and careful planning of therapeutic vaccine clinical trials is crucial to minimize design flaws, reduce loss of follow-ups and missing data while ensuring participant's safety and guarantee valid and accurate analyses and thus, better contribute towards an HIV cure.