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Changes in Vaginal Microbiota and Immune Mediators in HIV-1-Seronegative Kenyan Women Initiating Depot Medroxyprogesterone Acetate

Roxby, Alison C. MD, MSc; Fredricks, David N. MD; Odem-Davis, Katherine PhD; Ásbjörnsdóttir, Kristjana PhD; Masese, Linnet PhD; Fiedler, Tina L. BS; De Rosa, Stephen MD; Jaoko, Walter MBChB, MTM, PhD; Kiarie, James N. MBChB, MMed, MPH; Overbaugh, Julie PhD; McClelland, R. Scott MD, MPH

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 April 2016 - Volume 71 - Issue 4 - p 359–366
doi: 10.1097/QAI.0000000000000866
Basic and Translational Science

Background: Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation.

Methods: In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression.

Results: From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3–8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5–11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02).

Conclusions: Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.

Departments of *Medicine;

Microbiology, University of Washington, Seattle, WA;

Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA;

Departments of §Biostatistics;

Global Health;

Epidemiology; and

#Laboratory Medicine, University of Washington, Seattle, WA;

Departments of **Medical Microbiology;

††Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya;

‡‡Kenyatta National Hospital, Nairobi, Kenya; and

§§Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA.

Correspondence to: Alison C. Roxby, MD, MSc, University of Washington, PO Box 359909, Seattle, WA 98104 (e-mail: aroxby@uw.edu).

Supported by P01-HD64915 to J.O.—Project 2, R.S.M. from NIAID, an International Pilot Award to A.C.R. through a Center for AIDS Research award to the University of Washington (P30AI027757), which is supported by the following NIH Institutes and Centers (NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA). A.C.R. is supported by K23 HD071788-01A1 from NICHD. The funders had no role in study design, data collection and analysis, or preparation of the manuscript.

Presented as Poster 861 and at a themed oral discussion at the Conference on Retroviruses and Opportunistic Infections; February 23–26, 2015, Seattle, WA.

D.N.F. and T.L.F. have developed intellectual property related to the use of polymerase chain reaction for the diagnosis of bacterial vaginosis (BV). Refer to US patent 7625704 on use of polymerase chain reaction for diagnosis of BV. R.S.M. receives research funding and donated STD testing kits from Hologic/Gen-Probe Incorporated. R.S.M. has received payment for invited talks and donation of study product for a clinical trial of BV from Embil Pharmaceutical Company. The remaining authors have no funding or conflicts of interest to disclose.

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Received May 31, 2015

Accepted September 21, 2015

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