The successful demonstration that antiretroviral (ARV) drugs can be used in diverse ways to reduce HIV acquisition or transmission risks – either taken as pre-exposure prophylaxis (PrEP) by those who are uninfected or as early treatment for prevention (T4P) by those living with HIV – expands the armamentarium of existing HIV prevention tools. These findings have implications for the design of future HIV prevention research trials. With the advent of multiple effective HIV prevention tools, discussions about the ethics and the (...) feasibility of future HIV prevention trial designs have intensified. This article outlines arguments concerning the inclusion of newly established ARV-based HIV prevention interventions as standard of prevention in HIV prevention trials from multiple perspectives. Ultimately, there is a clear need to incorporate stakeholders in a robust discussion to determine the appropriate trial design for each study population. (shrink)

In 2010, randomized controlled trials (RCTs) of two different biomedical strategies to prevent HIV infection had positive findings. However, despite ongoing very high levels of HIV infection in some countries and population groups, it has been made clear by regulatory authorities that the evidence remains insufficient to support either product being made available outside of research contexts in the developing world for at least two years. In addition, prevention trials in endemic areas will continue to test new interventions against placebo. (...) But the judgments of evidentiary standards are never value-neutral. Using the recent trials and their contexts as case studies, we examine the basis for these decisions, which will potentially delay access to scientific innovation to the people who are most urgently in need of it. (shrink)

As new HIV prevention tools are developed, researchers face a number of ethical and logistic questions about how and when to include novel HIV prevention strategies and tools in the standard prevention package of ongoing and future HIV prevention trials. Current Joint United Nations Programme on HIV/AIDS /World Health Organization guidance recommends that participants in prevention trials receive ‘access to all state of the art HIV risk reduction methods’, and that decisions about adding new tools to the prevention package be (...) made in consultation with ‘all relevant stakeholders’. The guidance, however, leaves open questions of both process and implementation. In March 2009, the Global Campaign for Microbicides, UNAIDS and the Centers for Disease Control and Prevention convened a consultation to develop practical answers to these questions. Fifty-nine diverse participants, including researchers, ethicists, advocates and policymakers, worked to develop consensus criteria on when to include new HIV prevention tools in future trials. Participants developed a set of questions to guide decision-making, including: whether the method has been recommended by international bodies or adopted at a national level; the size of the effect and weight of the evidence; relevance to the trial population; whether the tool has been approved or introduced in the trial country; whether adding the tool might lead to trial futility; outstanding safety issues and status of the trial. Further work is needed to develop, implement and evaluate approaches to facilitate meaningful stakeholder participation in this deliberative process. (shrink)

Finding an effective microbicide that could substantially lower women’s risk of acquiring HIV infection is an ethical imperative. Women and girls continue to be disproportionally affected by HIV in sub-Saharan Africa. Ethics guidelines for conducting preventive HIV microbicide trials call for steps that intertwine biomedical research and public health. Ethical considerations include adequate studies of the safety of microbicides, the use of placebo controls in future trials once a microbicide is shown to be effective, whether leftover microbicide from a trial (...) that demonstrated efficacy should be made available to the public or used in the control group of a future trial, what preventive measures and treatment should be provided for trial participants during and after the research, and what constitute ‘fair benefits’ to the community or country when a trial is completed. The Global Campaign for Microbicides conducted a study of the benefits being provided to participants in microbicide trials and others, and found substantial evidence that researchers and sponsors are meeting the obligations stated in ethical guidelines. A cautionary tale of an HIV prevention trial that was prematurely halted demonstrates the need for engagement with the community where trials are carried out. (shrink)

The American Journal of Bioethics, Volume 12, Issue 3, Page 33-34, March 2012.

The American Journal of Bioethics, Volume 12, Issue 6, Page 33-34, June 2012.

The American Journal of Bioethics, Volume 12, Issue 3, Page 31-33, March 2012.

The number of women living with HIV/AIDS is increasing worldwide, and there is an urgent public health need to develop new user-initiated HIV prevention methods, including microbicides. Although funding for microbicide development has increased since 2000, financial support is provided predominantly by governmental agencies and private foundations. Many donors, including the US Agency for International Development (USAID) and the US National Institutes of Health (NIH), have policies that restrict how research funds may be used. Among these are the now-rescinded Mexico (...) City Policy, elements of the US Foreign Assistance Act, and restrictions on non-study-related care. The effect of these restrictions on the design and conduct of clinical research is poorly understood. As part of a recent mapping exercise conducted by the Global Campaign for Microbicides, we reviewed the impact of donor restrictions on seven HIV prevention trials. We found considerable confusion within the HIV prevention field as to whether and how Mexico City and other policies affect the use of research funds. We also found that these donor-imposed policies limited the level of care provided to trial participants and the types of capacity building projects undertaken. (shrink)

The American Journal of Bioethics, Volume 12, Issue 4, Page 21-22, April 2012.