In July 2012, based on evidence from two major trials, the United States Food and Drug Administration approved the use of combined oral tenofovir/emtricitabine as pre-exposure prophylaxis (PrEP) for people at high risk of HIV acquisition. PrEP effectiveness is marred by poor adherence, however, even in trial populations, thus it is not a magic bullet for HIV prevention. It is, however, the most effective biomedical HIV prevention intervention available for people at high risk of HIV, particularly those who have receptive sex and lack the power to negotiate condom use. Accordingly, there are compelling reasons to compare future experimental HIV prevention interventions against PrEP. The interests both of trial participants and of science are served by using PrEP as comparator: Not only would HIV incidence be reduced, but also the question of whether new interventions were superior to best proven interventions, in a given setting, would be answered comprehensively.
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Tenofovir gel works at a biological level as a form of topical pre- and post-exposure prophylaxis, but as taking an oral tablet is distinct from inserting a vaginal gel, the gel form and the oral form are usually seen as separate strategies.
Tenofovir (TDF) and emtricitabine (also known as FTC) are antiretroviral drugs that have synergistic action. The drug combination is marketed under the brand name Truvada.
Of note, the Bangkok PrEP trial was ethically problematic as it did not supply participants with clean injecting equipment.
ARV treatment is defined as “early” when it is administered in people whose CD4 cell levels are above 350.
This term was coined in 2007 in the UNAIDS Ethical Considerations document to end the confusion caused my multiple meanings of “standard of care.”
It could be argued that given such an effective intervention, the time has come to stop testing new approaches and to fully fund the global roll-out of early treatment for all people with HIV. This approach does not satisfy the requirement for HIV-negative people at high risk to be able to protect themselves, however, and research is likely to continue until this need has been met.
While in-depth discussion of these issues is beyond the scope of this paper, conducting a trial in an area where participants are denied access to a proven safe and effective intervention for social or political reasons is both inappropriate and exploitative.
At the time of writing, the only demonstration sites launched were in the United States, with others planned in two or three cities in Brazil.
Thanks to an anonymous peer reviewer for this point.
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Haire, B. It’s Time: The Case for PrEP as an Active Comparator in HIV Biomedical Prevention Trials. Bioethical Inquiry 12, 239–249 (2015). https://doi.org/10.1007/s11673-014-9565-9
- Biomedical research
- Human subjects research
- Regulatory issues
- Research ethics
- International/global health