Background: Intense activity is being directed at strategies for remission or eradication of HIV infection. However, current laboratory assays for HIV reservoir measurement are insufficient to demonstrate clearance of HIV and the best available test is to interrupt antiretroviral therapy (ART)?known as analytic treatment interruption (ATI)?for a defined period of time or until viral rebound occurs. Although ATIs are currently used in some HIV cure research, they raise important scientific and ethical questions.
Methods: A multidisciplinary group conducted an ethical analysis of the use of ATI in HIV cure research. The analysis examined the rationale for ATI and its potential scientific utility as well as the risks and burdens to study participants. Criteria for use of ATI in HIV cure studies were developed.
Results: Despite the ethical obligation to minimize research risks, there are limited data to directly inform risk assessment for ATIs in HIV cure trials. Experts have extrapolated from information from trials using longer repeated treatment interruptions, and from biological assays measuring effects of viral replication and inflammation. Despite these best efforts, it is difficult to ascertain the probability and magnitude of harm from a single ATI. There is also disagreement about the scientific utility of ATI in different types of studies. In spite of these uncertainties, studies involving ATIs must meet three basic ethical criteria:
1) a strong scientific justification for the ATI;
2) minimization of risks to study participants; and
3) a robust informed consent process.
Conclusions: Based on the ethical criteria identified in this analysis, investigators should carefully consider the acceptability of ATIs by providing a strong justification of an ATI and carefully select participants. Further work should be undertaken by clinical researchers in partnership with social scientists, behavioral researchers and ethicists to enhance the ethical conduct of studies employing ATIs.