Abstract
Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.
| Original language | English (US) |
|---|---|
| Pages (from-to) | e259-e268 |
| Journal | The Lancet HIV |
| Volume | 6 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2019 |
Bibliographical note
Funding Information:BJ reports grants from Gilead Sciences, outside the submitted work. JA reports fees from ViiV Healthcare, Gilead Sciences, Merck, Roche, and AbbVie, outside the submitted work. DHB reports grants from National Institutes of Health (NIH), Bill & Melinda Gates Foundation, US Department of Defense, the Defense Advanced Research Projects Agency, the Henry Jackson Foundation, amfAR, Gilead Sciences, Janssen Pharmaceuticals, and Ragon Institute, and personal fees from Merck, outside the submitted work. LD reports non-financial support from Ragon Institute and Delaney AIDS Research Enterprise Community Advisory Board, University of San Francisco, during the conduct of the study. SGD reports grants from Gilead Sciences, Merck, and ViiV Healthcare; and personal fees from AbbVie, BryoLogyx, Enochian Biosciences, Janssen Pharmaceuticals, and Shionogi, outside the submitted work. JE reports grants and personal fees from Janssen Pharmaceuticals, Gilead Science, and ViiV Healthcare, and personal fees from Merck, outside the submitted work. RTG reports grants and personal fees from Gilead Sciences, Merck, and Theratechnologies; and grants from ViiV Healthcare and Janssen Pharmaceuticals, outside the submitted work. GJH is an employee of Merck. RJ reports grants from The Elizabeth Taylor AIDS Foundation, during the conduct of the study; and grants from Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Healthcare, outside the submitted work. DK reports grants and personal fees from Gilead Sciences, Merck, and ViiV Healthcare; and personal fees from GlaxoSmithKline, Bionor, Abivax, and InnaVirVax, outside the submitted work. JvL is an employee of ViiV Healthcare. JWM reports grants from NIH, AIDS Clinical Trials Group, and Bill & Melinda Gates Foundation, during the conduct of the study; personal fees from University of Pittsburgh and Gilead Sciences; grant support from Gilead Sciences and Janssen Pharmaceuticals; and fees from Co-Crystal Pharma, all outside the submitted work; and has a patent (University of Pittsburgh, 8 815 829) issued. LJM reports personal fees and other support from ViiV Healthcare, grants from NIH, personal fees from UW University, outside the submitted work. VM reports grants from US NIH, during the conduct of the study; and grants from Gilead Sciences, Merck, ViiV Healthcare, LabCorp-Monogram, Roche, Abbott, and Janssen Pharmaceuticals, outside the submitted work. MLR reports grants from US Army Medical Research and Material Command, during the conduct of the study. JS reports grants from US NIH, and personal fees and non-financial support from Merck and IQVIA, outside the submitted work. SS declares that ViiV Healthcare donates medications for a clinical trial he co-directs. PT reports grants and personal fees from ViiV Healthcare, Merck, and Gilead Sciences, and grants from Inovio and US NIH, outside the submitted work. All other authors report no competing interests.
Publisher Copyright:
© 2019 Elsevier Ltd
