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Preservation HIV-1–Specific IFNγ+ CD4+ T-Cell Responses in Breakthrough Infections After Exposure to Tenofovir Gel in the CAPRISA 004 Microbicide Trial

Mureithi, Marianne W. PhD*,†; Poole, Danielle MPH*,†; Naranbhai, Vivek MD*,‡; Reddy, Shabashini MSc*; Mkhwanazi, Nompumelelo P. MSc*; Sibeko, Sengeziwe MBChB, MSc; Werner, Lise MSc; Karim, Quarraisha Abdool PhD‡,§; Karim, Salim Abdool MBChB, PhD‡,§; Ndung'u, Thumbi PhD*,†; Altfeld, Marcus MD, PhD*,†The CAPRISA004 Trial Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2012 - Volume 60 - Issue 2 - p 124–127
doi: 10.1097/QAI.0b013e31824f53a9
Brief Report: Basic and Translational Science

Abstract: The Centre for the AIDS Program of Research in South Africa 004 trial demonstrated reduction of sexual HIV-1 acquisition in women using a vaginal microbicide containing tenofovir. A better understanding of the consequences of antiretroviral-containing microbicides for immune responses in individuals with intercurrent HIV-1 infection is needed for future trials combining the use of microbicides with HIV-1 vaccines. Investigation of immune responses in women who acquired HIV-1 although using tenofovir gel showed significantly higher (P = 0.01) Gag-specific IFNγ+ CD4+ T-cell responses. The use of tenofovir-containing gel around the time of infection can modulate HIV-1 immunity, and these immunological changes need to be considered in future trials combining vaccines and microbicides.

*HIV Pathogenesis Program, Doris Duke Medical Research Institute and KwaZulu-Natal Research Institute for TB and HIV (KRITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Charlestown, MA

Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa

§Department of Epidemiology, Columbia University, New York, NY.

Correspondence to: Marcus Altfeld, MD, Associate Professor, Harvard Medical School, Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, 149 13th Street, Charlestown, MA 02129 (e-mail: maltfeld@partners.org).

Supported through the KwaZulu-Natal Research Institute for TB and HIV (K-RITH) and by a grant from the Doris Duke Charitable Foundation to MA. The parent trial (CAPRISA 004) was supported by the United States Agency for International Development (USAID), FHI360 [USAID co-operative agreement # GPO-A-00-05-00022-00, contract # 132119], and the Technology Innovation Agency (LIFElab) of the South African government's Department of Science & Technology. Tenofovir was provided by Gilead Sciences and the gel was manufactured and supplied for the CAPRISA 004 trial by CONRAD. The current studies are part of the CAPRISA TRAPS (Tenofovir gel Research for AIDS Prevention Science) Program, which is funded by CONRAD, Eastern Virginia Medical School [USAID co-operative grant #GP00-08-00005-00, subproject agreement # PPA-09-046]. The views expressed by the authors do not necessarily reflect the views of USAID, Gilead Sciences, Eastern Virginia Medical School or CONRAD.

The results from this study were presented in an oral presentation at the AIDS Vaccine meeting, 2011, Bangkok, Thailand.

The authors Q.A.K. and S.S.A.K. are coinventors with investigators from Gilead Sciences on two pending patents on tenofovir gel. The authors S.S.A.K. once received $2500 for serving on an Advisory Panel on PrEP for Merck. M.A. once received $1500 as a CME Honorarium from Gilead Science. M.W.M. was supported by the National Institutes of Health Office of the Director, Fogarty International Center, through the International Clinical Research Fellows Program at Vanderbilt (R24 TW007988).

The authors have no other conflicts of interest to disclose.

Received October 24, 2011

Accepted January 31, 2012

© 2012 Lippincott Williams & Wilkins, Inc.