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Vaginal Bacteria Associated with Increased Risk of HIV Acquisition in African Women (AIDS 2016 Conference Abstract)

Background: Disruptions of the vaginal microbiota have been associated with increased HIV-1 risk.  This study utilized molecular characterization of vaginal microbiota to test the hypothesis that specific vaginal bacteria are associated with increased risk of HIV-1 acquisition.
Methods: A nested case-control study was conducted in cohorts of women in Kenya, Uganda, Tanzania, Zambia, Botswana, and South Africa.  Vaginal microbiota was compared at the pre-seroconversion sample in women who acquired HIV-1 (cases) versus women in the same cohort who remained seronegative (controls).  Characterization of vaginal microbiota included deep sequence analysis of broad-range 16S rRNA gene polymerase chain reaction (PCR) products, and bacterium-specific quantitative PCR (qPCR) assays for selected bacteria.
Results: Among 349 women (87 cases and 262 controls), 40 were from a female sex worker cohort, 112 were from a cohort of pregnant and post-partum women, and 197 were HIV-seronegative women in discordant couples cohorts.  Their median age was 28 years (interquartile range 22-35) and 77 (22.1%) were pregnant.  Vaginal bacterial community diversity was higher in women who acquired HIV-1 compared to seronegative controls (mean Shannon Diversity Index 1.3 (standard deviation (SD) 1.0) versus 0.9 (SD 0.9), p=0.02.  Based on comparison of relative abundance in cases versus controls, 15 taxa were selected for qPCR testing.  Of these, Eggerthella species type-1, Gemella asaccharolytica, Leptotrichia/Sneathia, Megasphaera, and Mycoplasma hominis each showed a significant association with HIV-1 acquisition when undetectable levels were compared to tertiles representing increasing bacterial concentrations.  High correlation between species precluded including multiple species together in a single multivariable model.  These results remained significant after adjustment for age, pregnancy, contraceptive type, number of sex partners, frequency of sex, and recent unprotected intercourse (Figure 1).  
Conclusion:  Women’s HIV-1 susceptibility may be influenced by the presence and quantity of key vaginal bacteria, including a number of fastidious bacteria recently linked to bacterial vaginosis.
 

Periodic Presumptive Treatment for Vaginal Infections May Reduce the Incidence of Sexually Transmitted Bacterial Infections (J Infect Dis. 2016 Jun 15; 213 (12):1932-7)

Background: Bacterial vaginosis (BV) may increase women's susceptibility to sexually transmitted infections (STIs). In a randomized trial of periodic presumptive treatment (PPT) to reduce vaginal infections, we observed a significant reduction in BV. We further assessed the intervention effect on incident Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium infection.

Methods: Nonpregnant, human immunodeficiency virus-uninfected women from the United States and Kenya received intravaginal metronidazole (750 mg) plus miconazole (200 mg) or placebo for 5 consecutive nights each month for 12 months. Genital fluid specimens were collected every other month. Poisson regression models were used to assess the intervention effect on STI acquisition.

Results: Of 234 women enrolled, 221 had specimens available for analysis. Incidence of any bacterial STI (C. trachomatis, N. gonorrhoeae, or M. genitalium infection) was lower in the intervention arm, compared with the placebo arm (incidence rate ratio [IRR], 0.54; 95% confidence interval [CI], .32-.91). When assessed individually, reductions in STI incidences were similar but not statistically significant (IRRs, 0.50 [95% confidence interval {CI}, .20-1.23] for C. trachomatis infection, 0.56 [95% CI, .19-1.67] for N. gonorrhoeae infection, and 0.66 [95% CI, .38-1.15] for M. genitalium infection).

Conclusion: In addition to reducing BV, this PPT intervention may also reduce the risk of bacterial STI among women. Because BV is highly prevalent, often persists, and frequently recurs after treatment, interventions that reduce BV over extended periods could play a role in decreasing STI incidence globally.


A Prospective Cohort Study of Intimate Partner Violence and Unprotected Sex in HIV-Positive Female Sex Workers in Mombasa, Kenya (AIDS Behav. 2016 Sep; 20(9):2054-64)

We conducted a prospective cohort study to test the hypothesis that intimate partner violence (IPV) is associated with unprotected sex in HIV-positive female sex workers in Mombasa, Kenya. Women completed monthly visits and quarterly examinations. Any IPV in the past year was defined as ≥1 act of physical, sexual, or emotional violence by the current or most recent emotional partner ('index partner'). Unprotected sex with any partner was measured by self-report and prostate specific antigen (PSA) test. Recent IPV was associated with significantly higher risk of unprotected sex (adjusted relative risk [aRR] 1.91, 95 % CI 1.32, 2.78, p = 0.001) and PSA (aRR 1.54, 95 % CI 1.17, 2.04, p = 0.002) after adjusting for age, alcohol use, and sexual violence by someone besides the index partner. Addressing IPV in comprehensive HIV programs for HIV-positive women in this key population is important to improve wellbeing and reduce risk of sexual transmission of HIV.


 

Impact of community antiretroviral therapy coverage on HIV incidence in Kenyan female sex workers: A fifteen year prospective cohort study (AIDS. 2015 Nov; 29 (17):2279-86)

Background: Antiretroviral therapy (ART) reduces the infectiousness of people living with HIV, and increasing ART coverage may reduce HIV incidence in communities.  The effect of community ART coverage on the risk of HIV infection in female sex workers (FSWs) has not been evaluated.

Methods: We conducted a prospective study utilizing data from a cohort of FSWs in Mombasa, Kenya between 1998 and 2012.  HIV-negative women were asked to return for monthly follow-up visits, at which they were interviewed regarding risk behavior, examined for sexually transmitted infections, and tested for HIV infection.  We evaluated the impact of community ART coverage on women’s risk of becoming HIV infected.  Cox proportional hazards models including individual-level adjustment for known and suspected confounding factors were used.

Findings: A cohort of 1,404 FSWs contributed 4,335 woman-years of follow-up, with 145 acquiring HIV infection (incidence 3.35/100 woman-years).  The ART rollout in Mombasa District began in 2003, increasing steadily through 2012, when an estimated 52% of HIV-positive individuals were receiving treatment.  Community ART coverage was significantly inversely associated with HIV incidence (adjusted hazard ratio 0.97; 95% confidence interval 0.95-1.00; p=0.02), suggesting that each 1% increase in community ART coverage was associated with a 3% reduction in FSWs’ relative hazard for becoming HIV infected.

Interpretation: FSWs’ risk of HIV acquisition may be substantially reduced by increasing ART coverage in the general population. This effect could amplify declines in HIV incidence in the population as a whole, as fewer new infections would be transmitted from HIV-positive FSWs.

Women's Health Project 2016