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
Raphael J. Landovitz, Tao Li, Juan Yang, Melanie de Boer, Christoph C Carter, Moupali Das, Jared M. Baeten, Albert Liu, Karen W. Hoover, Connie Celum, Beatriz Grinsztejn, Sheldon Morris, Darrell P. Wheeler, Kenneth H. Mayer, Sarit A. Golub, Linda‐Gail Bekker, Souleymane Diabaté, Elske Hoornenborg, Janet J. Myers, Ashley A. Leech, Sheena McCormack, Philip A. Chan, Michael Sweat, Lynn T Matthews, Robert M. Grant, the Global F/TDF PrEP Study Team, Chris Beyrer, Joelle Brown, Jesse L. Clark, Paul W. Colson, Robyn Eakle, Jason E. Farley, Charlene Flash, Jorge Gallardo, Geoffrey S. Gottlieb, Alexandre Grangeiro, Renee Heffron, Sybil Hosek, Mark Hull, John Idoko, Irene Inwani, Helen Koenig, Ann Kurth, Shui Shan Lee, Kenneth Mayer, Souleymane Mboup, Jaimie P. Meyer, Anthony Mills, Andrew Mujugira, Pietro Pala, John Phoenix, Janice Piatt, Darren Russell, Eduard J. Sanders, R. Scott, Jae Sevelius, Hong Shang, Marc Siegel, Shobha Swaminathan, Vivian Robert Tamayo, Darrell H. S. Tan, Allan W. Taylor, Béa Vuylsteke
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.