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We compared human papillomavirus messenger RNA testing using urine, self-, and provider-collected samples for the detection of high-grade cervical cytology and assessed acceptability of urine self-collection among females who engage in sex work in Kenya. Participants found urine sampling comfortable, but high-risk human papillomavirus messenger RNA detection in urine samples was less likely to detect high-grade lesions than self- and provider-collected cervical samples.

We compared detection of Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis using dry and wet self-collected samples using brushes among females who engage in sex work in Mombasa, Kenya. Detection of T. vaginalis and N. gonorrhoeae in dry and wet samples was similar, but C. trachomatis detection in dry samples appeared lower.

No tool exists to stratify HIV risk in contemporary African female sex worker (FSW) populations. Data from a cohort of HIV-negative FSWs in Mombasa, Kenya from 2010 to 2017 were used to conduct a survival analysis assessing predictors of HIV infection. Stepwise regression was used to construct a multivariable model that formed the basis for the score. Seventeen HIV infections occurred over 1247 person-years of follow-up contributed by 670 women. Using depot medroxyprogesterone acetate (DMPA), having a curable sexually transmitted infection (STI), and being married contributed points to the score. HIV incidence was 0.85/100 person-years in a lower-risk group and 3.10/100 person-years in a higher-risk group. In a cohort with overall HIV incidence < 1.50/100 person-years, this risk score identified a subgroup of FSWs with HIV incidence > 3.00/100 person-years, which is the threshold used by the World Health Organization for initiating pre-exposure prophylaxis (PrEP). If validated in an external population, this tool could be useful for targeted PrEP promotion among higher-risk FSWs.

ObjectivesVaginal washing has been associated with reductions in cultivable Lactobacillus and an increased risk of both bacterial vaginosis (BV) and HIV infection. The effect of vaginal washing on the quantity of individual Lactobacillus species is not well characterised. This analysis tested the hypothesis that vaginal washing would be associated with a lower likelihood of Lactobacillus spp. detected by both culture and quantitative PCR (qPCR).MethodsWe conducted a cross-sectional study of 272 HIV-seronegative women enrolled in an open-cohort study in Mombasa, Kenya. Vaginal washing and sexual risk behaviours were assessed using face-to-face interviews. Vaginal Lactobacillus spp. were detected using cultivation and PCR methods, with L. crispatus, L. jensenii and L. iners concentrations measured using qPCR assays targeting the 16S rRNA gene. Poisson regression with robust SEs was used to assess associations between vaginal washing and Lactobacillus detection by culture and qPCR.ResultsEighty percent (n=217) of participants reported vaginal washing in the prior week. One-fifth (n=58) of participants had BV by Nugent score. In unadjusted analysis, vaginal washing was associated with a 45% decreased likelihood of Lactobacillus spp. detection by culture (prevalence ratio (PR): 0.55, 95% CI 0.37 to 0.82). Adjusting for age and condomless sex in the prior week did not change the magnitude of the association (adjusted PR (aPR): 0.56, 95% CI (0.37 to 0.85). Vaginal washing was associated with approximately a 40% reduction in L. crispatus detection (aPR: 0.57, 95% CI 0.36 to 0.92), but was not significantly associated with L. jensenii (aPR: 0.68, 95% CI 0.42 to 1.09) or L. iners detection (aPR: 1.03, 95% CI 0.92 to 1.15).ConclusionsVaginal washing in the prior week was associated with a significantly reduced likelihood of detecting cultivable Lactobacillus and L. crispatus by qPCR. Given associations between Lactobacillus detection and improved reproductive health outcomes, these results provide motivation for additional study of vaginal washing cessation interventions to improve vaginal health.

There are minimal data on the BVBlue test for diagnosis of bacterial vaginosis (BV) in Africa. Among 701 Kenyan women, compared with Nugent score ≥7, the BVBlue test had moderate sensitivity (81.9%; 95% confidence interval, 76.5%-86.5%) and high specificity (92.4%; 95% confidence interval, 89.5%-94.6%). This test may provide a complimentary approach to syndromic management.

The relationships between depressive symptoms, viral suppression, and condomless sex were examined in a prospective cohort study of 369 HIV-positive Kenyan female sex workers. Participants were screened for depressive symptoms at baseline and every six months until completion of the study (up to 66 months). HIV viral load (VL) was measured every six months and prostate specific antigen (PSA) testing in vaginal secretions was performed quarterly. Mild or greater depressive symptoms were found in 100 (27.1%) women and were associated with increased risk of detectable VL (aRR 1.41, 95%CI 0.97–2.07, p-value = 0.07), but were not associated with detectable PSA. The co-occurrence of PSA detection and detectable VL at the same visit suggests the potential for HIV transmission but was uncommon (2.4% of visits). The prevalence of depressive symptoms and the association with detectable VL suggests the need for screening and treatment of depression for comprehensive HIV care in this population.

Background: Female sex workers (FSWs) are at high risk for gender-based violence (GBV) and HIV infection. This study aimed to identify associations between GBV exposure in the past 12 months and biomarkers of physiologic stress and inflammation that may play a role in increased HIV risk among Kenyan FSWs. Materials and Methods: Participating women responded to a detailed questionnaire on GBV and mental health. Plasma was collected for assessment of systemic C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Hair proximal to the scalp was collected to measure cortisol concentration. CRP and IL-6 were measured by enzyme-linked immunosorbent assay, and hair cortisol concentration was determined by enzyme immunoassay. Log-transformed biomarker values were compared across GBV exposure categories using Kruskal–Wallis or Wilcoxon rank sum tests. Multivariable linear regression was used to explore associations between recent GBV and hair cortisol concentration. Results: Two hundred eighty-three women enrolled, of whom 112 (39.6%) reported physical, sexual, or emotional violence in the past 12 months, 134 (47.3%) reported more remote exposure, and 37 (13.1%) reported no exposure. CRP and IL-6 levels did not differ across groups (p = 0.57 and p = 0.62, respectively). Among 141 women who provided hair, cortisol concentrations were higher among recently exposed women compared to the other two groups combined (p = 0.02). In multivariable regression, recently exposed women had higher hair cortisol levels than remotely exposed or unexposed women (adjusted beta = 0.52, 95% confidence interval 0.02–1.02, p = 0.04). Conclusions: While CRP and IL-6 levels did not differ by GBV category, recent GBV was associated with increased hair cortisol concentration. GBV-related increases in cortisol could affect health outcomes and merit study in relation to HIV acquisition risk.

BACKGROUND Little is known about fertility desire in HIV-positive female sex workers. Fertility desire could increase HIV transmission risk if it was associated with condomless sex or lower adherence to antiretroviral therapy. METHODS A prospective cohort study was conducted among 255 HIV-positive female sex workers in Mombasa, Kenya. Using generalized estimating equations, fertility desire was evaluated as a risk factor for semen detection in vaginal secretions by prostate-specific antigen (PSA) test, a biomarker of condomless sex, detectable plasma viral load (VL), and HIV transmission potential, defined as visits with positive PSA and detectable VL. RESULTS The effect of fertility desire on PSA detection varied significantly by nonbarrier contraception use (P-interaction < 0.01). At visits when women reported not using nonbarrier contraception, fertility desire was associated with higher risk of semen detection [82/385, 21.3% vs. 158/1007, 15.7%; adjusted relative risk (aRR) 1.58, 95% confidence interval (CI): 1.12 to 2.23]. However, when women used nonbarrier contraception, fertility desire was associated with lower risk of PSA detection (10/77, 13.0% vs. 121/536, 22.6%; aRR 0.58, 95% CI: 0.35 to 0.94). Fertility desire was not associated with detectable VL (31/219, 14.2% vs. 128/776, 16.5%; aRR 0.82, 95% CI: 0.46 to 1.45) or higher absolute risk of transmission potential (10/218, 4.6% vs. 21/769, 2.7%; adjusted risk difference = 0.011, 95% CI -0.031 to 0.050). CONCLUSIONS Fertility desire was associated with higher risk of biological evidence of semen exposure when women were not using nonbarrier contraceptives. Low HIV transmission potential regardless of fertility desire suggests that the combination of condoms and antiretroviral therapy adherence was effective.

OBJECTIVE Many HIV-positive women now live well beyond menopause. Postmenopausal women are no longer at risk for pregnancy, and some studies suggest that they may use condoms less often than premenopausal women. This study tests the hypothesis that, in HIV-positive women who report trading sex for cash or in-kind payment, unprotected sex is more common at postmenopausal visits compared with premenopausal visits. DESIGN Prospective cohort study of HIV-positive women ≥16 years old in Mombasa, Kenya. METHODS At enrollment and monthly follow-up visits, participants completed a standardized interview. Study clinicians collected genital samples at enrollment and quarterly visits. Menopausal status was assessed annually. The primary outcome of unprotected sex was determined by detection of prostate specific antigen (PSA) in vaginal secretions. RESULTS This study followed 404 HIV-positive women who contributed 2753 quarterly examination visits. Detection of PSA was less frequent at postmenopausal visits compared with premenopausal visits [55/554, 10.5% versus 394/2199, 17.9%; relative risk (RR) 0.58, 95% confidence interval (CI): 0.39 to 0.87]. Adjusting for age diminished the association between menopause and PSA detection (adjusted RR 0.73, 95% CI: 0.47 to 1.14). At visits where women reported sexual activity in the past week, they reported similar rates of 100% condom use at postmenopausal and premenopausal visits (RR 0.99, 95% CI: 0.87 to 1.13). CONCLUSIONS In this population of high-risk HIV-positive Kenyan women, postmenopausal status was not associated with a greater risk of unprotected sex. The relationship between menopause and unprotected sex is likely context specific and may differ with varying risk groups, regions, and levels of exposure to sexual health education.

Background Certain vaginal bacteria may increase women’s risk for infection with high risk sub-types of human papilloma virus (hrHPV). The role of vaginal bacteria in hrHPV persistence is less well studied. We assessed associations between vaginal bacteria and hrHPV acquisition and persistence among Kenyan women in the placebo arm of the Preventing Vaginal Infections trial. Methods Nonpregnant, HIV-uninfected women aged 18–45 from Kenya and the United States were enrolled in a randomized trial of periodic presumptive treatment to reduce vaginal infections over 12 months. Genital fluid specimens collected at enrollment and every 2 months thereafter were tested for 14 hrHPV types using the Hologic APTIMA HPV assay. Quantitative PCR targeting the 16S rRNA gene from ten bacteria was used to measure bacterial concentrations in vaginal swabs. Multivariate multinomial logistic regression and multistate Markov models restricted to Kenyan placebo participants were used to assess associations between log10-transformed bacterial concentrations (categorized in tertiles) and hrHPV acquisition and persistence. Results Among the 84 Kenyan placebo participants, hrHPV was detected in 79/563 specimens (14%), with 16 episodes of persistent hrHPV (detection in >2 consecutive specimens; median duration was 6 months). Controlling for age, hormonal contraceptive use, and condom use, Lactobacillus jensenii concentration was positively associated with hrHPV incidence (adjusted odds ratio (aOR)=1.57; 95% CI 1.07–2.30); and Atopobium vaginae (aOR=1.40; 95% CI 1.02–1.93), Megasphaera species (aOR=1.39; 95% CI 1.03–1.88), and Mageeibacillus indolicus (aOR=1.48; 95% CI 1.09, 2.02) concentrations were positively associated with hrHPV persistence. BV (Nugent score >7) was not significantly associated with hrHPV incidence or persistence. Multistate Markov models did not indicate that bacterial concentrations were associated with transitions between HPV detection states. Conclusion These findings suggest that higher concentrations of certain vaginal bacteria may increase risk of hrHPV incidence and persistence. Future work with more frequent sampling could provide additional insight into factors associated with hrHPV persistence. Disclosure No significant relationships.

Some studies suggest that higher body mass index is associated with increased susceptibility to bacterial vaginosis (BV), but results are conflicting. Methods Female sex workers aged 16 to 45 years and participating in an open, prospective cohort study in Mombasa, Kenya between 2000 and 2014 were included in this analysis. Up to 2 years of follow-up were included per woman. Body mass index (BMI) was categorized as underweight (≤18.5), normal (18.5-24.9), overweight (25-29.9), and obese (≥30). Bacterial vaginosis was assessed using Nugent scores. Generalized estimating equations were used to estimate relative risks of the association between BMI and BV. Results At baseline, 32.1% (n = 625) of 1946 women had BV. Half of women were overweight (31.1%, n = 606) or obese (20.1%, n = 391). Participants contributed 14,319 follow-up visits. Adjusting for age, compared to women with normal BMI, overweight (adjusted relative risk, 0.91; 95% confidence interval, 0.81-1.02) and obese (adjusted relative risk, 0.82; 95% confidence interval, 0.71-0.94) women were at lower risk for BV (joint P = 0.03). Conclusions Obese women had a nearly 20% lower risk of BV compared with women with normal BMI. Potential mechanisms for this effect, including possible effects of diet, obesity-associated changes in the gut microbiome, and systemic estrogen levels, should be explored.

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.

Background Excessive alcohol intake has been associated with poor adherence to antiretroviral therapy (ART). The impact of alcohol on viral suppression is particularly important among groups at high risk of HIV transmission, such as female sex workers (FSWs). Few studies have directly evaluated the association between alcohol use and HIV viral load. We hypothesized that hazardous or harmful alcohol use is associated with detectable plasma viral load among HIV-positive FSWs. Methods A prospective cohort study was conducted among HIV-positive FSWs in Mombasa, Kenya. Hazardous or harmful alcohol use was assessed yearly and defined as an Alcohol Use Disorders Identification Test (AUDIT) score ≥7. Detectable viral load was assessed every six months and defined as ≥180 c/mL. Adherence measures were collected monthly and included late ART refill (>48 hours) and self-reported adherence, using both a validated self-rating scale of ability to take medication and visual analog scale (VAS) of ART use in the last month. Generalized estimating equations were used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CI). Results This analysis included 366 participants followed monthly between October 2012 and March 2018. At baseline, AUDIT scores indicated hazardous alcohol use (AUDIT 7–15) in 14.3%, harmful alcohol use (AUDIT 16–19) in 1.4%, and alcohol dependency (AUDIT ≥20) in 1.4% of participants. After adjusting for potential confounders, a combined exposure including hazardous, harmful, and dependent alcohol use was not associated with detectable viral load (aRR 1.10, 95%CI 0.63–1.92) or late ART refill (aRR 1.13, 95%CI 0.82–1.56), but was associated with lower self-rated ability to take medication (aRR 2.38, 95%CI 1.42–3.99) and a lower rate of self-reported perfect ART adherence by VAS (aRR 2.62, 95%CI 1.84–3.71). Conclusions In this FSW cohort, while participants reporting hazardous, harmful, or dependent alcohol use were not more likely to have a detectable viral load, they were more likely to report lower ART adherence. These results suggest that interventions targeting alcohol use among this population of FSWs may not have a large impact on viral suppression.

BACKGROUND Little is known about the natural history of Mycoplasma genitalium (MG) infection in women. We retrospectively tested archived vaginal fluid samples to assess MG prevalence, incidence, persistence, recurrence and antimicrobial resistance markers among women participating in the Preventing Vaginal Infections trial, a randomized trial of monthly presumptive treatment to reduce vaginal infections. METHODS High-risk, nonpregnant, HIV-negative women aged 18 to 45 years from Kenya and the United States were randomized to receive metronidazole 750 mg + miconazole 200 mg intravaginal suppositories or placebo for 5 consecutive nights each month for 12 months. Clinician-collected swabs containing cervicovaginal fluid were tested for MG using Hologic nucleic acid amplification testing at enrollment and every other month thereafter. Specimens that were MG+ underwent additional testing for macrolide resistance-mediating mutations by DNA sequencing. RESULTS Of 234 women enrolled, 221 had available specimens and 25 (11.3%) had MG at enrollment. Among 196 women without MG at enrollment, there were 52 incident MG infections (incidence, 33.4 per 100 person-years). Smoking was independently associated with incident MG infection (adjusted hazard ratio, 3.02; 95% confidence interval, 1.32-6.93), and age less than 25 years trended toward an association (adjusted hazard ratio, 1.70; 95% confidence interval, 0.95-3.06). Median time to clearance of incident MG infections was 1.5 months (interquartile range, 1.4-3.0 months). Of the 120 MG+ specimens, 16 specimens from 15 different women were macrolide resistance-mediating mutation positive (13.3%), with no difference by country. CONCLUSIONS M. genitalium infection is common among sexually active women in Kenya and the Southern United States. Given associations between MG and adverse reproductive health outcomes, this high burden of MG in reproductive-aged women could contribute to substantial morbidity.

OBJECTIVES: Vaginal washing has been associated with reductions in cultivable Lactobacillus and an increased risk of both bacterial vaginosis (BV) and HIV infection. The effect of vaginal washing on the quantity of individual Lactobacillus species is not well characterized. This analysis tested the hypothesis that vaginal washing would be associated with a lower likelihood of Lactobacillus spp. detected by both culture and quantitative PCR (qPCR). METHODS: We conducted a cross-sectional study of 272 HIV-seronegative women enrolled in an open-cohort study in Mombasa, Kenya. Vaginal washing and sexual risk behaviours were assessed using face-to-face interviews. Vaginal Lactobacillus spp. were detected using cultivation and PCR methods, with L. crispatus, L. jensenii, and L. iners concentrations measured using qPCR assays targeting the 16S rRNA gene. Poisson regression with robust standard errors was used to assess associations between vaginal washing and Lactobacillus detection by culture and qPCR. RESULTS: Eighty percent (n=217) of participants reported vaginal washing in the prior week. One-fifth (n=58) of participants had BV by Nugent score. In unadjusted analysis, vaginal washing was associated with a 45% decreased likelihood of Lactobacillus spp. detection by culture (prevalence ratio (PR): 0.55, 95%CI 0.37–0.82). Adjusting for age and condomless sex in the prior week did not change the magnitude of the association (adjusted PR (aPR): 0.56, 95%CI (0.37, 0.85). Vaginal washing was associated with approximately a 40% reduction in L. crispatus detection (aPR: 0.57, 95%CI 0.36–0.92), but was not significantly associated with L. jensenii (aPR: 0.68, 95%CI 0.42–1.09) or L. iners detection (aPR: 1.03, 95%CI 0.92–1.15). CONCLUSIONS: Vaginal washing in the prior week was associated with a significantly reduced likelihood of detecting cultivable Lactobacillus and L. crispatus by qPCR. Given associations between Lactobacillus detection and improved reproductive health outcomes, these results provide motivation for additional study of vaginal washing cessation interventions to improve vaginal health.

OBJECTIVE: The objective of this study was to understand temporal trends in the contribution of different genital tract infections to HIV incidence over 20 years of follow-up in a cohort of high-risk women. DESIGN: A prospective cohort study. METHODS: We performed monthly evaluations for HIV vaginal yeast bacterial vaginosis Trichomonas vaginalis Neisseria gonorrhoeae nonspecific cervicitis herpes simplex virus type two (HSV-2) genital ulcer disease (GUD) and genital warts. We used Cox regression to evaluate the association between sexually transmitted infections (STIs) and HIV acquisition over four time periods (1993-1997 1998-2002 2003-2007 2008-2012). Models were adjusted for age workplace sexual risk behaviour hormonal contraceptive use and other STIs. The resulting hazard ratios were used to calculate population attributable risk percentage (PAR%). RESULTS: Between 1993 and 2012 1964 women contributed 6135 person-years of follow-up. The overall PAR% for each infection was prevalent HSV-2 (48.3%) incident HSV-2 (4.5%) bacterial vaginosis (15.1%) intermediate microbiota (7.5%) vaginal yeast (6.4%) T. vaginalis (1.1%) N. gonorrhoeae (0.9%) nonspecific cervicitis (0.7%) GUD (0.8%) and genital warts (-0.2%). Across the four time periods the PAR% for prevalent HSV-2 (40.4% 61.8% 58.4% 48.3%) and bacterial vaginosis (17.1% 19.5% 14.7% 17.1%) remained relatively high and had no significant trend for change over time. The PAR% for trichomoniasis gonorrhoea GUD and genital warts remained less than 3% across the four periods. CONCLUSION: Bacterial vaginosis and HSV-2 have consistently been the largest contributors to HIV acquisition risk in the Mombasa Cohort over the past 20 years. Interventions that prevent these conditions would benefit womens health and could reduce their risk of becoming infected with HIV.

Introduction Evidence suggests that women with bacterial vaginosis (BV) are at increased risk for infection with high risk sub-types of human papilloma virus (hrHPV). Among women participating in a randomised trial of periodic presumptive treatment (PPT) to reduce vaginal infections including BV, we previously reported reductions in bacterial STIs among women receiving PPT compared to placebo. In the current analysis, we assessed the effect of PPT on acquisition of HR-HPV among Kenyan women enrolled in the trial. Methods Nonpregnant, HIV-uninfected women aged 18–45 from Kenya and the United States were randomised to receive intravaginal metronidazole 750 mg plus miconazole 200 mg or matching placebo for 5 consecutive nights each month for 12 months. Genital specimens were collected every other month. Following completion of the trial, enrollment and follow-up specimens from participants at the three sites in Kenya were tested for hrHPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) using the Hologic APTIMA HPV assay. Poisson regression models were used to assess the intervention effect on hrHPV incidence and time to first detection of hrHPV. Results Among 176 Kenyan women participating in the trial, 168/176 (95%) had specimens available for analysis (intervention n=84; placebo n=84). Baseline hrHPV prevalence was 17% (n=29) and similar by arm. Among participants without detectable hrHPV at enrollment, 26 participants had hrHPV detected during 114.6 person-years (incidence=22.7/100 person-years), with similar incidence in the intervention versus placebo arm (21.7/100 person-years versus 23.6/100 person-years; incidence rate ratio [IRR]=0.92, 95% CI 0.42, 1.99). Conclusions This intervention, which significantly reduced BV over 12 months, did not impact acquisition of hrHPV. However, the high incidence of hrHPV provides evidence in support HPV vaccination efforts in this region.

Background As access to antiretroviral therapy in sub-Saharan Africa continues to expand, more women with HIV can expect to survive through their reproductive years. Modern contraceptives can help women choose the timing and spacing of childbearing. However, concerns remain that women with HIV who use non-barrier forms of modern contraception may engage in more condomless sex because of their decreased risk of unintended pregnancy. We examined whether non-barrier modern contraceptive use by HIV-positive female sex workers was associated with increased frequency of recent condomless sex, measured by detection of prostate-specific antigen (PSA) in vaginal secretions. Methods Women who were HIV-positive and reported transactional sex were included in this analysis. Pregnant and post-menopausal follow-up time was excluded, as were visits at which women reported trying to get pregnant. At enrollment and quarterly follow-up visits, a pelvic speculum examination with collection of vaginal secretions was conducted for detection of PSA. In addition, women completed a structured face-to-face interview about their current contraceptive methods and sexual risk behavior at enrollment and monthly follow-up visits. Log-binomial generalized estimating equations regression was used to test for associations between non-barrier modern contraceptive use and detection of PSA in vaginal secretions and self-reported condomless sex. Data from October 2012 through September 2014 were included in this analysis. Results Overall, 314 women contributed 1,583 quarterly examination visits. There was minimal difference in PSA detection at contraceptive-exposed versus contraceptive-unexposed visits (adjusted relative risk [aRR] 1.28, 95% confidence interval [95% CI] 0.93–1.76). There was a higher rate of self-reported condomless sex at visits where women reported using modern contraceptives, but this difference was not statistically significant after adjustment for potential confounding factors (aRR 1.59, 95% CI 0.98–2.58). Conclusion Non-barrier methods of modern contraception were not associated with increased risk of objective evidence of condomless sex.

Background This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women.

We have recently reported high levels of fluoroquinolone resistance in a single region of Kenya. In this manuscript, we report high prevalence of fluoroquinolone resistance (53.2%) in Neisseria gonorrhoeae isolates from four clinics in three additional regions of Kenya. These findings highlight the need to change first-line treatment in these settings and the need to evaluate empiric management guidelines for treatment of gonococcal infection in Kenya.

OBJECTIVES Resistant viruses may emerge in the female genital tract during antiretroviral therapy (ART). Our objective was to identify predictors of drug-resistant HIV-1 RNA in genital secretions after initiation of nonnucleoside reverse transcriptase inhibitor-based therapy. DESIGN We conducted a prospective cohort study with periodic evaluation of plasma and genital swab samples for HIV-1 RNA levels and antiretroviral resistance mutations. METHODS First-line ART was initiated in 102 women. Plasma and genital HIV-1 RNA levels were measured at months 0, 3, 6, and 12. Genotypic resistance testing was performed for samples from all participants with RNA >1000 copies per milliliter at month 6 or 12. Cox regression analysis was used to identify factors associated with incident genital tract resistance. RESULTS Detectable genital tract resistance developed in 5 women, all with detectable plasma resistance (estimated incidence, 5.5/100 person-years of observation). Treatment interruption >48 hours, adherence by pill count, adherence by visual analog scale, and baseline plasma viral load were associated with incident genital tract resistance. In multivariate analysis, only treatment interruption was associated with risk of detectable genital tract resistance (adjusted hazard ratio: 14.2; 95% confidence interval: 1.3 to 158.4). CONCLUSIONS Treatment interruption >48 hours during nonnucleoside reverse transcriptase inhibitor-based therapy led to a significantly increased risk of detecting genotypically resistant HIV-1 RNA in female genital tract secretions. Patient- and program-level interventions to prevent treatment interruptions could reduce the risk of shedding-resistant HIV-1 during ART.

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). Conclusions 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.

SummaryWe evaluated the prevalence and correlates of intimate partner violence in the past year by a regular male partner in HIV-positive female sex workers in Mombasa, Kenya. This cross-sectional study included HIV-positive women ≥18 years old who reported engagement in transactional sex at the time of enrolment in the parent cohort. We asked 13 questions adapted from the World Health Organization survey on violence against women about physical, sexual, or emotional violence in the past year by the current or most recent emotional partner (index partner). We used standardised instruments to assess socio-demographic and behavioural characteristics as possible correlates of intimate partner violence. Associations between intimate partner violence and these correlates were evaluated using univariate and multivariate logistic regression. Overall, 286/357 women (80.4%) had an index partner, and 52/357 (14.6%, 95% confidence interval 10.9%-18.2%) reported intimate partner violence by that partner in the past year. In multivariate analysis, women with severe alcohol problems (adjusted odds ratio 4.39, 1.16-16.61) and those experiencing controlling behaviours by the index partner (adjusted odds ratio 4.98, 2.31-10.74) were significantly more likely to report recent intimate partner violence. Recent intimate partner violence was common in HIV-positive female sex workers. Interventions targeting risk factors for intimate partner violence, including alcohol problems and partner controlling behaviours, could help to reduce recurrent violence and negative health outcomes in this key population. Language: en

Intravaginal practices (IVP) are common among African women and are associated with HIV acquisition. A behavioral intervention to reduce IVP is a potential new HIV risk-reduction strategy. Fifty-eight HIV-1-uninfected Kenyan women reporting IVP and 42 women who denied IVP were followed for 3 months. Women using IVP attended a skill-building, theory-based group intervention occurring weekly for 3 weeks to encourage IVP cessation. Vaginal swabs at each visit were used to detect yeast, to detect bacterial vaginosis, and to characterize the vaginal microbiota. Intravaginal insertion of soapy water (59%) and lemon juice (45%) was most common among 58 IVP women. The group-counseling intervention led to a decrease in IVP from 95% (54/58) at baseline to 0% (0/39) at month 3 (p=0.001). After 3 months of cessation, there was a reduction in yeast on vaginal wet preparation (22% to 7%, p=0.011). Women in the IVP group were more likely to have a Lactobacillus iners-dominated vaginal microbiota at baseline compared to controls [odds ratio (OR), 6.4, p=0.006] without significant change in the microbiota after IVP cessation. The group counseling intervention was effective in reducing IVP for 3 months. Reducing IVP may be important in itself, as well as to support effective use of vaginal microbicides, to prevent HIV acquisition.

Objectives The WHO recommends that men who have sex with men (MSM) reporting unprotected receptive anal intercourse (RAI) and either multiple partners or a partner with a sexually transmitted infection (STI) in the past 6 months should be presumptively treated for asymptomatic rectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. We evaluated this recommendation in a cohort of ‘high-risk’ MSM in Coastal Kenya. Methods We assessed presence of genitourinary and rectal symptoms, and determined prevalence and 3-month incidence of rectal NG and CT infections. We performed nucleic acid amplification testing of urine and rectal swab samples collected from MSM followed prospectively, and assessed predictive values of the WHO algorithm at baseline screening. Results Of 244 MSM screened, 240 (98.4%) were asymptomatic, and 147 (61.3%) reported any RAI in the past 6 months. Among 85 (35.4%) asymptomatic MSM meeting criteria for the WHO presumptive treatment (PT) recommendation, we identified 20 with rectal infections (six NG, 12 CT and two NG–CT co-infections). Among 62 asymptomatic MSM who did not meet criteria, we identified seven who were infected. The sensitivity and specificity of the WHO algorithm were 74.1% (95% CI 53.7% to 88.9%) and 45.8% (95% CI 36.7% to 55.2%), respectively. The 3-month incidence of any rectal NG or CT infection in asymptomatic men reporting any RAI was 39.7 (95% CI 24.3 to 64.8) per 100 person-years. Conclusions About one-third of asymptomatic MSM were eligible to receive PT for NG and CT infections. Among MSM who would qualify for PT of rectal STIs, the number needed to treat in order to treat one infection was four. Our results support the value of the WHO screening algorithm and recommended PT strategy in this population.

Herpes simplex virus type 2 (HSV-2) infected women have a higher prevalence of bacterial vaginosis (BV) compared to HSV-2-seronegative women. To explore the temporal association between these conditions, we evaluated the frequency of BV episodes before and after HSV-2 acquisition in a prospective study of 406 HSV-2/HIV-1-seronegative Kenyan women, of whom 164 acquired HSV-2. Incident HSV-2 was associated with increased likelihood of BV (adjusted OR, 1.28; 95% CI, 1.05–1.56; P = .01). Our findings strengthen the evidence for a causal link between genital HSV-2 infection and disruption of the vaginal microbiota.

Few prospective studies have evaluated the association between alcohol use and STI acquisition among African women. We examined the association between baseline drinking frequency and STIs in a cohort of Kenyan women reporting transactional sex. The association between alcohol use and STI differed significantly by HIV status. Among 139 HIV-positive women, STI acquisition was significantly associated with consuming 1–7 drinks/week and marginally associated with ≥8 drinks/week in unadjusted analyses. However, no association between alcohol use and STIs was observed among 335 HIV-negative women. Addressing alcohol use within comprehensive HIV care may also reduce the burden of STIs among high-risk women.

Background Intravaginal practices including vaginal washing have been associated with HIV-1 acquisition. This association may be mediated by mucosal disruption, changes in vaginal flora or genital tract inflammatory responses. Reducing vaginal washing could lower women’s risk of HIV-1 acquisition. Methods 23 HIV-1 seronegative women who reported current vaginal washing were recruited from a prospective cohort study of high-risk women in Mombasa, Kenya. A theoretical framework including information–motivation–behavioural skills and harm reduction was implemented to encourage participants to reduce or eliminate vaginal washing. At baseline and after 1 month, we evaluated vaginal epithelial lesions by colposcopy, vaginal microbiota by Nugent’s criteria and vaginal cytokine milieu using ELISA on cervicovaginal lavage specimens. Results The most commonly reported vaginal washing substance was soap with water (N=14, 60.9%). The median frequency of vaginal washing was 7 (IQR 7–14) times per week. After 1 month, all participants reported cessation of vaginal washing (p=0.01). The probability of detecting cervicovaginal epithelial lesions was lower (OR 0.48; 95% CI 0.20 to 1.16; p=0.10) and the likelihood of detecting Lactobacillus by culture was higher (OR 3.71, 95% CI 0.73 to 18.76, p=0.11) compared with baseline, although these results were not statistically significant. There was no change in the prevalence of bacterial vaginosis. Most cytokine levels were reduced, but these changes were not statistically significant. Conclusions A theory-based intervention appeared to have a positive effect in reducing vaginal washing over 1 month. Larger studies with longer follow-up are important to further characterise the effects of vaginal washing cessation on biological markers.

Objectives To assess the burden of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in high-risk HIV-1 negative men who have sex with men (MSM) in Africa. Methods Before the start of a pre-exposure prophylaxis trial, HIV-1 negative volunteers were screened for sexually transmitted infection (STI) including CT and NG, using a highly sensitive and specific nucleic acid amplification test. Samples positive for CT by Aptima testing, were evaluated for the presence of lymphogranuloma venereum (LGV) serovars using an in-house PCR assay. All men were asked to submit a urine specimen, and all had a rectal swab collected by a clinician. Men were asked if they had dysuria, urethral or rectal discharge, or rectal pain. Results 43 HIV-1 negative MSM were screened, of whom 13 reported sex with men only; the majority (27/43) reported sex work. One volunteer had dysuria and another, rectal pain. Eleven MSM (26%, 95% CI 14% to 41%) had infections with either or both pathogens. Homosexual men had a higher prevalence of any infection than bisexual men (46% vs 17%, p=0.04), and all cases of rectal infections, including one with CT, two with NG and two with CT/NG co-infection. All patients with CT were negative for LGV. One patient with a rectal NG infection reported rectal pain. Conclusions A remarkably high burden of STI infection was found among HIV-1 negative MSM. Most (12/13) infections, including three of four rectal NG infections, were subclinical. These findings suggest that high-risk MSM will benefit from effective STI screening in Kenya.

Background Trachoma is thought to be endemic over large parts of Southern Sudan, but empirical evidence is limited. While some areas east of the Nile have been identified as highly endemic, few trachoma surveys have been conducted in the remainder of the country. This study aimed to determine whether trachoma constitutes a problem to public health in Northern Bahr-el-Ghazal and Unity State, both located west of the Nile. Methods and Principal Findings Trachoma rapid assessments (TRA) were conducted between July and September 2009. Seven villages in Northern Bahr-el-Ghazal State and 13 villages in Unity State were surveyed; an average of 50 children (age 1–9 years) and 44 women (age 15 years and above) were examined per village. Samples for analysis using the APTIMA Combo-2 nucleic acid amplification test (NAAT) were collected from participants with active trachoma in eight villages in Unity State. In Northern Bahr-el-Ghazal State, only three children with active trachoma (trachomatous inflammation follicular (TF) and/or trachomatous inflammation intense (TI)) and two women with trichiasis (TT) were found, in two of the seven villages surveyed. In Unity State, trachoma was endemic in all thirteen villages surveyed; the proportion of children with active trachoma ranged from 33% to 75% between villages, while TF in children ranged from 16% to 44%. Between 4% to 51% of examined women showed signs of TT. Samples from active trachoma cases tested using the NAAT were positive for Chlamydia trachomatis infection for 46.6% of children and 19.0% of women. Conclusions Trachoma presents a major problem to public health Unity State, while the disease is of low priority in Northern-Bahr-el-Ghazal State. Implementation of a population-based prevalence survey is now required in Unity State to generate baseline prevalence data so that trachoma interventions can be initiated and monitored over time.

Background Intravaginal practices have been associated with HIV-1 acquisition. This may be mediated by mucosal disruption, changes in vaginal flora, or inflammatory responses in the genital tract. Reducing vaginal washing could lower women9s risk of HIV-1 acquisition. We conducted a prospective study to test the hypothesis that a theory-based intervention would reduce vaginal washing in a cohort of high-risk Kenyan women. We collected pilot data on changes in biological markers that might help to explain the relationship between vaginal washing and HIV-1. Methods HIV-1 seronegative women who reported current vaginal washing were recruited from a prospective cohort study of high-risk women in Mombasa, Kenya. A theoretical framework including Information Motivation and Behaviour and Harm Reduction was implemented to encourage participants to reduce or eliminate vaginal washing. At baseline and after 1 month, we evaluated vaginal epithelial lesions by colposcopy, vaginal flora by Nugent9s criteria, and vaginal cytokine milieu using ELISA on cervicovaginal lavage specimens. Results Twenty-three women were enrolled. The most commonly reported vaginal washing substance was soap and water (N=14, 60.9%). The median frequency of vaginal washing per week was 7 (IQR 0–14). After one week, 21 (91.3%) participants reported cessation of vaginal washing. After 1 month, all participants reported cessation of vaginal washing (p≤0.001 for comparison of baseline to follow-up prevalence). The average number of cervicovaginal epithelial lesions by colposcopy decreased after 1 month compared to baseline (Mean [SD] 0.4 [0.6] vs 0.2 [0.5]; coefficient −0.14; 95% CI −0.29 to 0.01; p=0.08). Although there was no change in the prevalence of BV (OR 1.00, 95% CI 0.42 to 2.38; p=1.00]), these pilot data suggest that the likelihood of detecting Lactobacillus by culture might increase after cessation of vaginal washing (2 [8.8%] vs 6 [26.1%]; OR 3.71, 95% CI 0.73 to 18.76, p=0.11). Most cytokine levels were reduced after cessation of vaginal washing, but in this small, time-limited sample none of these changes were statistically significant. Conclusions A theory-based intervention was highly successful in reducing vaginal washing over 1 month. This pilot study suggests the need for future studies with a larger sample size and longer follow-up to determine the effects of vaginal washing cessation on the cervicovaginal epithelium, vaginal flora, and inflammatory markers.

The sequestration ofPlasmodium falciparum-infected erythrocytes (pRBC) away from the peripheral circulation is a property of all field isolates. Here we have examined the pRBC of 111 fresh clinical isolates from children with malaria for a number of adhesive features in order to study their possible coexpression and association with severity of disease. A large number of adhesion assays were performed studying rosetting, giant rosetting, and binding to CD36, intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, thrombospondin, heparin, blood group A, and immunoglobulins. Suspension assays were performed at the actual parasitemia of the isolate, while all the static adhesion assays were carried out at an equal adjusted parasitemia. The ability to bind to multiple receptors, as well as the ability to form rosettes and giant rosettes, was found to be more frequent among isolates from children with severe versus mild malaria (P= 0.0015). Rosettes and giant rosettes were more frequent for children with severe malaria, and the cell aggregates were larger and tighter, than for those with mild disease (P= 0.0023). Binding of immunoglobulins (97% of isolates) and of heparin (81% of isolates) to infected erythrocytes was common, and binding to heparin and blood group A was associated with severity of disease (P= 0.011 andP= 0.031, respectively). These results support the idea that isolates that bind to multiple receptors are involved in the causation of severe malaria and that several receptor-ligand interactions work synergistically in bringing about severe disease.

We sought genetic evidence for the importance of host-parasite interactions involving CD36 in severe malaria. We identified a non-sense mutation in Cd36 gene and looked at the influence of this mutation on the outcome of malaria infection in 693 African children with severe malaria and a similar number of ethnically matched controls. We showed that heterozygosity for this mutation is associated with protection from severe disease (OR 0.74, 95% CI 0.55-0.99; p=0.036). These findings suggest that this Cd36 mutation might have a complex effect on malaria infection by decreasing parasite sequestration, and also by decreasing host immune responses.

Background Vaginal washing has been associated with an increased risk of bacterial vaginosis (BV) and a decreased likelihood of vaginal Lactobacillus colonisation. We sought to determine whether a lower prevalence of Lactobacillus colonisation in women reporting vaginal washing was independent of the effect of BV. Methods We conducted a cross-sectional study of 273 HIV-negative female sex workers enrolled in an open cohort study in Mombasa, Kenya. Vaginal washing and sexual risk behaviours were assessed using structured face-to-face interviews. Lactobacillus species were detected by plating vaginal swabs on both Rogosa and Columbia 5% sheep blood agars. We used tetramethylbenzidine agar subculture to assess H 2 O 2 -production. BV was detected by Gram stain. Log-binomial regression was used to assess correlates of Lactobacillus colonisation, including vaginal washing, controlling for BV. Results Two-hundred eighteen participants (80%) reported vaginal washing in the past week (median frequency per week = 14; range 1–35). Lactobacillus species were detected in 50/218 (23%) participants who reported vaginal washing versus 23/55 (42%) who did not report this practise. Similarly, H 2 O 2 -producing Lactobacillus species were detected in 13/218 (6%) participants who reported vaginal washing versus 10/55 (18%) who did not. After controlling for age, unprotected sex, and BV, vaginal washing was associated with a lower likelihood of any Lactobacillus (adjusted relative risk [aRR] = 0.55; 95% confidence interval [CI] 0.37–0.81) and H 2 O 2 -producing Lactobacillus (aRR = 0.33; 95% CI 0.15–0.73). Conclusion Vaginal washing was associated with a lower likelihood of any Lactobacillus and H 2 O 2 -producing Lactobacillus species detected by culture. The results of our adjusted analysis suggest that the effect of vaginal washing on lactobacilli is not mediated entirely through the higher prevalence of BV associated with this practise. Prospective studies will be important to determine whether cessation of vaginal washing could improve vaginal health by promoting vaginal colonisation with Lactobacillus.

Recent work suggests that IgG and IgM from nonimmune human serum (natural antibodies) bind to the surface of Plasmodium falciparum-infected erythrocytes and contribute to rosette formation by stabilizing the interaction between infected and uninfected erythrocytes. Here we show, in both laboratory clones and field isolates, that only IgM but not IgG is detected on the surface of infected cells. In field isolates, there was a strong positive correlation between IgM binding and rosette formation (Spearman's rank correlation coefficient p = 0.804, P < 0.001). Both rosette formation and IgM binding were associated with severe malaria, although statistical analysis indicates that rosette formation is the more strongly associated variable. Rosette formation, but not IgM binding, was also associated with malarial anemia. We conclude that IgM is the predominant class of natural antibodies binding to the surface of infected erythrocytes. However, we could not confirm previous suggestions that infected erythrocytes are coated with nonimmune IgG, which could lead to their interaction with host Fcgamma receptors.