Clinical Trials Will Play a Vital Role in Charting the Path to an HIV Cure
The search for a cure for HIV has recently been given fresh impetus by the widely reported case of an HIV-positive individual named Timothy Brown who has remained free of detectable virus for four years (and counting) after a complex series of treatments for cancer. Although too impractical and risky for general application, the outcome of Brown’s treatment is viewed as a compelling “proof of concept” that a cure for HIV infection is possible. Now, in order to build the knowledge necessary to develop a safe and broadly accessible curative therapy, clinical trials of approaches that may be able to deplete HIV from the body or contribute to drug-free control of the virus are being launched. In light of the importance of this research, the AIDS Policy Project, amfAR, Project Inform, and TAG recently sponsored a workshop on the conduct of clinical trials relevant to the goal of curing HIV infection. The event took place on 20–21 April 2011 at the Renaissance Harborplace Hotel in Baltimore.
The 52 workshop participants—including scientists, community members, ethicists, research funders and regulators—discussed key issues, including:
- criteria for advancing potential therapeutic candidates into human trials
- the ethical and regulatory aspects of trials involving individuals at low risk of illness in which the main potential benefit is advancement of scientific knowledge
- laboratory tests to measure the impact of interventions
- the design of trials and appropriate endpoints (measurements of trial outcomes)
Among the priorities that emerged is the need to rigorously compare the variety of tests that are used to measure very small amounts of HIV in individuals on long-term suppressive antiretroviral therapy (ART). In order to quantify the effect of an intervention on HIV reservoirs, tests need to be able to reliably show relatively tiny differences in amounts of virus. To imagine the scale of the challenge, imagine trying to use a bathroom scale to measure the difference in weight between one and two grains of sand.
Another important consideration is the use of analytic interruptions of ART to assess the impact of an intervention—the ultimate test, in the view of many. Because the rebound in viral load that occurs after stopping ART is associated with potentially dangerous bursts of inflammation, parameters to minimize risk to trial participants were recommended.
Moving forward, there was widespread agreement about the need to work on a range of issues to facilitate future HIV cure-related clinical trials. These included increasing awareness and knowledge regarding cure-related research among regulators and clinical trial review bodies (such as institutional review and community advisory boards), promoting increased funding for the field, and ensuring coordination and information sharing among scientists conducting relevant studies. The sponsoring organizations will be following up on the advocacy issues identified at the workshop and a full meeting report is forthcoming.
For an updated list of relevant articles, clinical trials, and other resources (including the clinical research workshop report as soon as it is available), see TAG’s HIV Cure-Related Research Resource Page.