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Background

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

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Background

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  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. Background • 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

  3. Background Normal Flora Bacterial Vaginosis Intermediate Flora • 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)

  4. Hypothesis ♀ HIV+/ve • ♂ HIV-1-infected women with BV have an increased risk of female-to-maleHIV transmission than women with normal vaginal flora

  5. Methods • 2,236 south and East African HIV-serodiscordant couples • HIV+/ve woman • CD4 ≥ 250 cells/mm3, 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

  6. 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

  7. Analysis Methods -6 Months-3 MonthsTime 0 Vaginal flora HIV-1-seroconversion Primary Analysis Sensitivity Analysis • Primary outcome • Genitally-linked HIV transmission

  8. Enrollment characteristics

  9. 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%

  10. Incidence of HIV-1 transmission to men, by the vaginal flora category of women

  11. Risk of female-to-male HIV-1 transmission among men whose female partners had BV vs. normal vaginal flora *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. Log10HIV RNA concentration in plasma and female genital secretions compared by vaginal flora category *After controlling for plasma HIV RNA

  13. Hypotheses to explain 3-fold increase risk of ♀ to ♂ HIV transmission • BV increases female genital concentration of HIV RNA • Modest increase (0.2 log10) in genital HIV RNA concentration • BV increases proportion of “infectious” HIV • Lactobacilli are virucidal against HIV (Klebanoff, 1999 • 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)

  14. Suggested Future Directions *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 • Exploit human microbiome to promote normal vaginal flora • Frequent presumptive treatment (McClelland, 2008) • Probiotic lactobacilli (Hemmerling, 2011)

  15. 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

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