Journal article
Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women
NR Klatt, R Cheu, K Birse, AS Zevin, M Perner, L Noël-Romas, A Grobler, G Westmacott, IY Xie, J Butler, L Mansoor, LR McKinnon, JAS Passmore, QA Karim, SSA Karim, AD Burgener
Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2017
Abstract
Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women. We investigated whether vaginal microbiota modulated tenofovir gel microbicide efficacy in the CAPRISA (Centre for the AIDS Program of Research in South Africa) 004 trial. Two major vaginal bacterial community types-one dominated by Lactobacillus (59.2%) and the other where Gardnerella vaginalis predominated with other anaerobic bacteria (40.8%)-were identified in 688 women profiled. Tenofovir reduced HIV incidence by 61%(P = 0.013) in Lactobacillus-dominant women but only 18% (P = 0.644) in women with non-Lactobacillus bacteria, a threefold difference in efficacy. Detectible mucosal tenofovir was lo..
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Awarded by Manitoba Health Research Council
Funding Acknowledgements
The data reported in this manuscript are tabulated in the main paper and in the supplementary materials. Funding for this research was provided by the Canadian Institutes of Health Research (CIHR) (A.D.B., L.R.M., S.S.A.K.) (grant TMI 138658), the Department of Pharmaceutics at the University of Washington (N.R.K.), and the Public Health Agency of Canada (A.D.B, G.W.). M.P. is a recipient of a studentship of the CIHR and the Manitoba Health Research Council. We thank S. McCorrister, M. Abou, M. Cook, and C. Miller for technical assistance; N. Yende for statistical support; and J. Schellenberg for primary bacterial isolates. We also thank all investigators of the CIHR Team Grant, including K. Broliden, K. Arnold, D. Lauffenburger, K. Hasselrot, and A. Tjernlund. The funding agencies did not have any role in the study design; the collection, analysis, and interpretation of data; or the writing of the paper or its submission for publication. The CAPRISA 004 tenofovir gel trial was funded principally by the U.S. Agency for International Development, grants through FHI360, and CONRAD for product manufacturing, with support from the South African Department of Science and Technology (DST). We thank the DST and the South African National Research Foundation for supporting the specimen repository; A. Kashuba for tenofovir concentration data; the CAPRISA 004 study team, including J. Frohlich, A. Kharsany, K. Mlisana, C. Baxter, T. Gengiah, N. Samsunder, and S. Sibeko, as well as the study clinicians, counselors, pharmacists, statisticians, and fieldwork, data quality, laboratory and administrative staff for their contributions; and the women who participated in the CAPRISA 004 trial.