iPrEx study

iPrEx study The iPrEx study was a landmark randomized, double-blind, placebo-controlled clinical trial that evaluated oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for HIV pre-exposure prophylaxis (PrEP) among men who have sex with men and transgender women. The trial informed clinical guidelines, regulatory decisions, and public health strategies across multiple jurisdictions and influenced subsequent trials and implementation programs.

Background

The trial emerged amid global discussions involving World Health Organization, Centers for Disease Control and Prevention, UNAIDS, and national agencies in contexts influenced by prior research such as trials involving azidothymidine and combination antiretroviral therapies evaluated during the era of International AIDS Conference debates. Investigators were motivated by epidemiological data from cohorts in San Francisco, New York City, Lima, São Paulo, Rio de Janeiro, Bangkok, and Cape Town, and by prior pharmacologic research at institutions like Gilead Sciences and academic centers including University of California, San Francisco and Columbia University. Ethical and regulatory frameworks from bodies such as Food and Drug Administration, National Institutes of Health, Ethics Committee of the World Medical Association, and national regulatory authorities guided study design.

Study design and methods

iPrEx was a multicenter Phase II/III randomized, double-blind, placebo-controlled trial conducted at clinical sites coordinated by investigators affiliated with institutions including University of Washington, Harvard University, Johns Hopkins University, Fred Hutchinson Cancer Research Center, and community partners such as Gay Men's Health Crisis and LGBT Foundation. The protocol enrolled 2,499 HIV-seronegative participants assigned to daily oral FTC/TDF or matched placebo, with follow-up visits for laboratory monitoring, HIV testing, and behavioral counseling in line with standards from World Health Organization guidance and local institutional review boards like those at Universidade de São Paulo and National Institute of Allergy and Infectious Diseases. Adherence assessment combined self-report, pill counts, and pharmacologic measurement of drug levels processed at reference laboratories including Centers for Disease Control and Prevention and academic pharmacology cores. Outcomes were prespecified in the statistical analysis plan overseen by data monitoring committees similar to those used in trials at Johns Hopkins Bloomberg School of Public Health and modeled on precedent trials such as those coordinated by Family Health International.

Results

The trial demonstrated a relative risk reduction in HIV acquisition among FTC/TDF recipients compared to placebo, with effectiveness estimates influenced by adherence as measured by drug concentrations in plasma and peripheral blood mononuclear cells analyzed at sites including Fred Hutchinson Cancer Research Center and Harvard School of Public Health. Subgroup analyses considered geographic sites in Peru, Ecuador, Brazil, Thailand, South Africa, and the United States and examined correlates similar to those explored in cohort studies at Emory University and University of California, Los Angeles. The primary efficacy findings prompted discussion among regulators such as the Food and Drug Administration and public health bodies including Public Health England and provincial health ministries in Ontario and British Columbia.

Safety and adverse events

Safety monitoring revealed generally mild adverse events, with renal function and bone mineral density evaluated using assays and imaging modalities available at clinical centers like Massachusetts General Hospital and Karolinska Institutet; routine laboratory safety oversight paralleled standards from National Institutes of Health clinical trials networks. Reports addressed concerns raised in other antiretroviral studies conducted at sites such as Mayo Clinic and University College London Hospital, with data safety monitoring boards and regulatory advisors from institutions including World Health Organization and European Medicines Agency reviewing event rates. The safety profile influenced labeling decisions by manufacturers and prescribing guidance disseminated by professional bodies like the Infectious Diseases Society of America and International AIDS Society.

Impact and subsequent research

iPrEx catalyzed policy change, influencing guideline updates by organizations including World Health Organization, Centers for Disease Control and Prevention, National AIDS Control Organization (India), and specialist societies such as British HIV Association. It inspired implementation studies and demonstration projects in urban centers like San Francisco, New York City, London, Rio de Janeiro, and Bangkok and informed subsequent randomized trials and pragmatic studies including those led by groups at University of Cape Town, Imperial College London, McGill University, and University of British Columbia. The trial spurred development of alternative PrEP modalities evaluated in later trials sponsored by entities like Gilead Sciences, ViiV Healthcare, and public-private consortia involving Bill & Melinda Gates Foundation and Wellcome Trust, and fostered research into long-acting formulations, topical microbicides, and implementation strategies studied at centers such as Fred Hutchinson Cancer Research Center and Johns Hopkins University.

Category:HIV/AIDS clinical trials