Successful Discontinuation of the Placebo Arm and Provision of an Effective HIV Prevention Product After a Positive Interim Efficacy Result: The Partners PrEP Study Experience

Ndase, Patrick MBChB, MPH*; Celum, Connie MD, MPH*,†,‡; Campbell, James MD, MS§; Bukusi, Elizabeth MBChB, MMed, MPH, PhD*,‖,¶,#; Kiarie, James MBChB, MPH; Katabira, Elly MBChB**; Mugo, Nelly MBChB, MMed, MPH*,‖; Tumwesigye, Elioda MBChB, MPH††; Wangisi, Jonathan MBChB, MSc‡‡; Were, Edwin MBChB, MMed, MPH§§; Brantley, Justin*; Donnell, Deborah MPH*,‖‖; Baeten, Jared M. MD, PhD*,†,‡

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 June 2014 - Volume 66 - Issue 2 - p 206–212
doi: 10.1097/QAI.0000000000000141
Epidemiology and Prevention

Background: Dissemination of research results to study participants and stakeholders and provision of proven effective products in the immediate post-trial period are core elements of the conduct of biomedical HIV prevention clinical trials. Few biomedical HIV prevention trials have demonstrated HIV protection with novel interventions, and thus, communication of positive trial results and provision of an effective product have not been tested in many situations.

Methods: In July 2011, the independent Data and Safety Monitoring Board of the Partners PrEP Study, a randomized, placebo-controlled efficacy trial of daily oral antiretroviral preexposure prophylaxis (PrEP) for HIV prevention among 4747 African heterosexual HIV serodiscordant couples, recommended discontinuation of the trial's placebo arm due to demonstration of PrEP efficacy. We describe dissemination of results, discontinuation of the placebo arm, and provision of active PrEP to participants' formerly assigned placebo.

Results: Within 72 hours, of the Data and Safety Monitoring Board meeting the study results were publicly released and disseminated to stakeholders and study participants. Within 3 months, the study protocol was modified to permit participants initially assigned to the study's placebo arm to be offered active PrEP. Of the 1418 participants initially randomized to placebo who were clinically eligible to receive PrEP, 89.1% (1264/1418) consented.

Conclusions: Prompt dissemination of a positive HIV prevention trial result and subsequent provision of effective product to research participants was feasible and efficient for >4700 HIV serodiscordant couples in East Africa. The extent to which study sponsors can assure continued product access to research participants remains a subject of discussion for future HIV prevention clinical trials.

Departments of *Global Health;

Medicine;

Epidemiology, University of Washington, Seattle, WA;

§Centers for Disease Control and Prevention, Entebbe, Uganda;

Department of Obstetrics and Gynecology, University of Nairobi and Kenyatta National Hospital, Nairobi, Kenya;

Center for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya;

#Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA;

**Infectious Disease Institute, Makerere University, Kampala, Uganda;

††Kabwohe Clinical Research Center, Kabwohe, Uganda;

‡‡The AIDS Support Organization, Kampala, Uganda;

§§Department of Reproductive Health, Moi University, Eldoret, Kenya; and

‖‖Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Correspondence to: Jared M. Baeten, MD, PhD, Department of Global Health, University of Washington, 325 Ninth Avenue, Box 359927, Seattle, WA 98104 (e-mail: jbaeten@u.washington.edu).

Members of the Partners PrEP Study Team are listed in the Appendix.

Supported by The Bill and Melinda Gates Foundation (Grant OPP47674; http://www.gatesfoundation.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors designed and executed the study, had full access to the raw data, performed all analyses, wrote the manuscript, and had final responsibility for the decision to submit for publication.

The authors have no conflicts of interest to disclose.

Received February 28, 2014

Accepted February 28, 2014

© 2014 by Lippincott Williams & Wilkins