Type 1 Human Immunodeficiency Virus (HIV-1) Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis: Pooled Analysis From 72 Global Studies
Author:
Landovitz Raphael J1, Tao Li2, Yang Juan2, de Boer Melanie2, Carter Christoph2, Das Moupali2, Baeten Jared M2, Liu Albert3, Hoover Karen W4, Celum Connie5, Grinsztejn Beatriz6, Morris Sheldon7, Wheeler Darrell P8, Mayer Kenneth H9, Golub Sarit A10, Bekker Linda-Gail11ORCID, Diabaté Souleymane12, Hoornenborg Elske13, Myers Janet3, Leech Ashley A14, McCormack Sheena15, Chan Philip A16, Sweat Michael17, Matthews Lynn T18, Grant Robert19, , Beyrer Chris, Brown Joelle, Clark Jesse, Colson Paul, Eakle Robyn, Farley Jason, Flash Charlene A, Gallardo Jorge, Gottlieb Geoffrey, Grangeiro Alexandre, Heffron Renee, Hosek Sybil, Hull Mark, Idoko John, Inwani Irene, Koenig Helen, Kurth Ann, Lee Shui-shan, Mayer Kenneth, Mboup Souleymane, Meyer Jaimie, Mills Anthony, Mujugira Andrew, Pala Pietro, Phoenix John, Piatt Janice, Russell Darren, Sanders Eduard, Scott Rachel, Sevelius Jae, Shang Hong, Siegel Marc, Swaminathan Shobha, Tamayo Vivian, Tan Darrell, Taylor Allan, Vuylsteke Bea
Affiliation:
1. UCLA Center for Clinical AIDS Research and Education , Los Angeles, California , USA 2. Gilead Sciences, Inc , Foster City, California , USA 3. Bridge HIV, San Francisco Department of Public Health , San Francisco, California , USA 4. US Centers for Disease Control and Prevention , Atlanta, Georgia , USA 5. University of Washington , Seattle, Washington , USA 6. Instituto Nacional de Infectologia Evandro Chagas/Fundação Oswaldo Cruz (Fiocruz) , Rio de Janeiro , Brazil 7. UC San Diego Health , San Diego, California , USA 8. State University of New York , New Paltz, New York , USA 9. Fenway Health and Harvard Medical School , Boston, Massachusetts , USA 10. Hunter College , New York, New York , USA 11. The Desmond Tutu HIV Centre, University of Cape Town , Cape Town , South Africa 12. Centre de Recherche du CHU de Québec–Université Laval , Quebec , Canada 13. Public Health Service of Amsterdam , Amsterdam , Netherlands 14. Department of Health Policy, Vanderbilt University School of Medicine , Nashville, Tennessee , USA 15. MRC Clinical Trials Unit at University College London , London , United Kingdom 16. Brown University , Providence, Rhode Island , USA 17. Medical University of South Carolina , Charleston, North Carolina , USA 18. The University of Alabama at Birmingham , Birmingham, Alabama , USA 19. Department of Medicine, University of California San Francisco , San Francisco, California , USA
Abstract
Abstract
Background
Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.
Methods
HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.
Results
Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63–.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2−3, 4−6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9–5.3), .24 (.060–.95), .27 (.12–.60), and .054 (.008–.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports.
Conclusions
Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.
Funder
Gilead Sciences, Inc. California HIV-1 Research Program National Institutes of Health National Institutes of Mental Health Doris Duke Foundation Medical Research Council
Publisher
Oxford University Press (OUP)
Cited by
4 articles.
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