Addressing the challenges of HIV prevention trials
By Kristen Jill Kresge
The prestigious US Institute of Medicine (IOM), an independent advisory group on public health policy, convened a series of meetings last year on the methodological challenges of conducting non-vaccine HIV prevention trials. The final report based on these proceedings, as well as site visits by IOM committee members to clinical trial sites in Uganda and South Africa, was just issued in February (www.nap.edu/catalog/12056.html).
These meetings and the final report were commissioned by the Bill & Melinda Gates Foundation. The foundation requested that the IOM committee focus in particular on research involving microbicides and pre-exposure prophylaxis (PrEP; see VAX May 2006 Spotlight article, Treatment as prevention), and provide recommendations on how future trials could be conducted in a way that could increase the likelihood of success and enable donors to optimally invest their limited financial resources.
At the public meetings, committee members and leading researchers in the field discussed several of the most-pressing issues surrounding the design and conduct of large-scale HIV prevention trials (see Advisory Panel considers complexities of HIV prevention trials, IAVI Report, January-February 2007 and Optimizing HIV prevention research, IAVI Report, March-April 2007).
The final report outlines the recent spate of late-stage clinical trials in the HIV prevention field that have failed to provide any benefit in reducing the risk of HIV infection (see Spotlight, this issue), leading the authors to conclude that, “A near-perfect biomedical intervention for preventing HIV infection is unlikely to be available in the near future.”
The importance of accurately estimating HIV incidence is among the main issues highlighted in the report. This became a concern when multiple prevention trials were stopped early because the HIV incidence observed during the trial was lower than initial estimates on which the trial was based (see VAX July 2007 Primer on Understanding HIV Incidence). The IOM committee recommends that all late-stage trials be designed based on incidence estimates collected through traditional cohort follow-up studies of HIV-uninfected individuals in the communities where the trial will occur. The authors also suggest that this estimate should be corroborated by at least one other source.
High pregnancy rates during HIV prevention trials, and the impact on retention of female volunteers, was another critical issue that was discussed at the committee meetings and is addressed in the report (see Primer, this issue). Female volunteers are typically not allowed to receive the experimental intervention during pregnancy because of potential safety risks to the fetus. But their exclusion from the trial can confound the results. On this issue, the authors suggest that researchers should try to determine the safety of the intervention in pregnant women to determine circumstances where women could potentially continue to participate in HIV prevention trials while pregnant.
The report also outlines several other ways that trials can be designed to more efficiently determine the influence of behavior and adherence on the final results.