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Bacterial vaginosis increases the risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples Craig R. Cohen, Jairam.

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Presentation on theme: "Bacterial vaginosis increases the risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples Craig R. Cohen, Jairam."— Presentation transcript:

1 Bacterial vaginosis increases the risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples Craig R. Cohen, Jairam R. Lingappa, Jared M. Baeten, Musa O. Ngayo, Carol A. Spiegel, Ting Hong, Deborah Donnell, Connie Celum, Saidi Kapiga, Sinead Delany, Elizabeth A. Bukusi, for the Partners in Prevention HSV/HIV Transmission Study Team

2 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine 2 33 million HIV-infected persons –60% in sub-Saharan Africa Women account for the majority of cases Antiretroviral therapy associated with 96% reduction in HIV transmission –Only 37% qualifying for ART receive ART (UNAIDS, 2010) New strategies to reduce HIV transmission required Background

3 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Background Bacterial vaginosis (BV) –Common disorder 30% - 55% in sub- Saharan Africa –Polymicrobial Decrease in lactobacilli –Associated with 60% increase Male-to- Female HIV transmission (Atashili, 2008) –Associated with increase genital tract HIV RNA (Coleman, 2007) 3 Normal Flora Intermediate Flora Bacterial Vaginosis

4 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Hypothesis HIV-1-infected women with BV have an increased risk of female-to-male HIV transmission than women with normal vaginal flora 4 ♀ HIV+/ve ♂

5 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Methods 2,236 south and East African HIV- serodiscordant couples –HIV+/ve woman CD4 ≥ 250 cells/mm 3, HSV-2 +/ve, no ART (enrollment) Vaginal Gram stain enrollment, & every 3-months Plasma VL: enrollment, 3, 6, 12 months, study exit Genital VL: 6 month visit –HIV-/ve man HIV testing every 3-months 5

6 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Laboratory Methods Gram stain per Nugent’s criteria –Normal vaginal flora: 0 – 4 –Intermediate vaginal flora: 5 – 6 –Bacterial vaginosis: 7 – 10 HIV testing: –HIV genotyping (env & gag) to confirm transmission linkage (Campbell, 2011) HIV RNA testing –Lower limit detection = 240 copies per mL/swab 6

7 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Analysis Methods Primary outcome –Genitally-linked HIV transmission 7 -6 Months-3 MonthsTime 0 HIV-1- seroconversion Vaginal flora Sensitivity Analysis Primary Analysis

8 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Enrollment characteristics 8 HIV infected female HIV uninfected male Age, years, mean, IQR30 (25-35)35 (30-42) Education, years, median, IQR 8 (6-10)9 (7-12) Male circumcisedN/A1228 (54.9%) East vs. southern Africa1452 (64.9%) Married1647 (73.7%) Years lived together, median, IQR 5 (2-9) Unprotected sex with partner past month 682 (30.5%) Plasma HIV, log 10 copies/mL, median, IQR 3.95 ( )N/A CD4 count, cells/mm 3 median, IQR 481 ( )N/A

9 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Vaginal flora at enrollment and follow-up 14,791 female visits –10,472 (70.8%) with vaginal Gram stain data –Vaginal flora across quarterly visits (Median) BV: 34.9% Intermediate flora: 22.8% Normal flora: 42.8% 9

10 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Incidence of HIV-1 transmission to men, by the vaginal flora category of women 10 HIV casesHIV incidence/100 person-years All seroconversions Seroconversions with missing BV status 7- Seroconversions with BV status Normal vaginal flora90.76 Abnormal vaginal flora Intermediate vaginal flora BV312.91

11 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Risk of female-to-male HIV-1 transmission among men whose female partners had BV vs. normal vaginal flora 11 ModelHRAdjusted HR* Primary analysis Pre-visit BV 3.62 ( )3.06 ( ) Sensitivity Analyses Current visit BV 5.30 ( )3.97 ( ) More severe BV status 7.19 ( )6.98 ( ) *Fixed covariates: age, geographic region, partner HSV-2 status, circumcision, randomization assignment and STD; Time-dependent covariates: pregnancy, hormonal contraception, plasma HIV-1 RNA, unprotected sex act with study partner, CD4 count, outside partners, number of sex act with study partner, and genital ulcer disease.

12 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Log 10 HIV RNA concentration in plasma and female genital secretions compared by vaginal flora category Vaginal FloraLog 10 HIV Mean ± SD P-Value vs. normal vaginal flora P-Value* vs. normal vaginal flora Genital HIV RNA Normal vaginal flora 3.04 ± 0.99N/A Intermediate vaginal flora 3.25 ± BV 3.23 ± Plasma HIV RNA Normal vaginal flora 3.81 ± 1.00N/A Intermediate vaginal flora 3.96 ± N/A BV 3.99 ± N/A 12 *After controlling for plasma HIV RNA

13 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Hypotheses to explain 3-fold increase risk of ♀ to ♂ HIV transmission 1.BV increases female genital concentration of HIV RNA –Modest increase (0.2 log 10 ) in genital HIV RNA concentration 2.BV increases proportion of “infectious” HIV –Lactobacilli are virucidal against HIV (Klebanoff, BV indirectly increases HIV susceptibility in male partner –Female & male genital microbiota are shared (Bukusi, 2011; Gray, 2009) –Bacteria may activate Langerhans cells and CD4+ T-cells (Donoval, 2006) 13

14 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Suggested Future Directions Exploit human microbiome to promote normal vaginal flora –Frequent presumptive treatment (McClelland, 2008) –Probiotic lactobacilli (Hemmerling, 2011) 14 *Association of abnormal vaginal flora with male-to-female HIV-1 transmission among HIV-1 serodiscordant couples in sub-Saharan Africa. M.O. Ngayo, TUPE188

15 Department of Obstetrics, Gynecology & Reproductive Sciences School of Medicine Acknowledgements University of Washington –Partners in Prevention HSV/HIV Coordination Center –Central Laboratories Study sites and Principal Investigators Study participants Bill & Melinda Gates Foundation Kenya Medical Research Institute –Center for Microbiology Laboratory –Director, KEMRI DF/Net Research University of Witwatersrand –Contract Laboratory Services National Institutes of Health 15


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