Innate immune activation was a strong predictor of HIV acquisition in women at risk for HIV in CAPRISA 004. Identifying the cause(s) of activation could enable targeted prevention interventions. In this study, plasma concentrations of lipopolysaccharide, soluble CD14, and intestinal fatty acid–binding protein did not differ between subjects who did or did not subsequently acquire HIV nor were these levels correlated with plasma cytokines or natural killer cell activation. There was no difference between HIV acquirers and non-acquirers in the chemokine and cytokine responses of peripheral blood mononuclear cells stimulated with TLR2, 4, or 7/8 agonists. Further studies are required.
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*Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa;
†HIV Pathogenesis Program, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa;
‡Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
§Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY;
‖Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA;
¶KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; and
#Medgar Evers College, City University of New York, Brooklyn, NY.
Correspondence to: Salim S. Abdool Karim, PhD, Centre for the AIDS Programme of Research In South Africa (CAPRISA), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, KwaZulu Natal, South Africa (e-mail: email@example.com).
V. N., N. S., and N. G. S. contributed equally to the work.
S. S. A. K. and Q. A. K. were the co-principal investigators of the CAPRISA 004 trial of tenofovir gel. S. S. A. K. and Q. A. K. are also co-inventors of 2 pending patents (61/354.050 and 61/357,892) of tenofovir gel against HSV-1 and HSV-2 with scientists from Gilead Sciences. Gilead Sciences did not have any role in the experiments or analyses presented here.
This work was supported by the South African HIV/AIDS Research Platform (SHARP), and US National Institutes for Health FIC K01-TW007793. V. Naranbhai was supported by LIFELab and the Columbia University-South Africa Fogarty AIDS International Training and Research Program (AITRP, grant D43 TW000231). W. H. Carr was supported by a Massachusetts General Hospital Physician Scientist Development Award. T. Ndung'u holds the South African Department of Science and Technology/National Research Foundation Research Chair in Systems Biology of HIV/AIDS and is also supported by the Howard Hughes Medical Institute. M. Altfeld is a Distinguished Clinical Scientist of the Doris Duke Charitable Foundation. D. C. Douek, N. G. Sandler, and A. Roque were supported by the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.The parent trial (CAPRISA 004) was supported by the United States Agency for International Development (USAID), FHI360 ([USAID co-operative agreement GPO-A-00-05-00,022-00, contract 132119), and the Technology Innovation Agency (LIFElab) of the South African government's Department of Science & Technology. 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 GP00-08-00,005-00, 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. We thank the US National Institutes for Health's Comprehensive International Program of Research on AIDS (CIPRA grant AI51794) for the research infrastructure. Clinical trials registration number of parent trial: NCT00441298.
Author contributions: All the authors contributed to the design of the sub-study. V. N. designed the study. V. N., N. S. and N. G. S. designed and executed the experiments, performed the data collection and analysis. T. N., M. A., D. C. D. and S. S. A. K. supervised the data collection. S. S. A. K. and Q. A. K. designed, conducted, and analyzed the parent CAPRISA 004 trial. All authors reviewed and approved the final manuscript.
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Received November 08, 2012
Accepted February 06, 2013