Linnet Masese

Treatment with antiretroviral therapy is not associated with increased sexual risk behavior in Kenyan female sex workers.

Objective:The objective of this study was to test the hypothesis that sexual risk behavior would increase following initiation of antiretroviral therapy (ART) in Kenyan female sex workers (FSWs). Design:Prospective cohort study. Setting:FSW cohort in Mombasa, Kenya, 1993–2008. Subjects:Eight hundred and ninety-eight women contributed HIV-1-seropositive follow-up visits, of whom 129 initiated ART. Intervention:Beginning in March 2004, ART was provided to women qualifying for treatment according to Kenyan National Guidelines. Participants received sexual risk reduction education and free condoms at every visit. Main outcome measures:Main outcome measures included unprotected intercourse, abstinence, 100% condom use, number of sexual partners, and frequency of sex. Outcomes were evaluated at monthly follow-up visits using a 1-week recall interval. Results:Compared with non-ART-exposed follow-up, visits following ART initiation were not associated with an increase in unprotected sex [adjusted odds ratio (AOR) 0.86, 95% confidence interval (CI) 0.62–1.19, P = 0.4]. There was a nonsignificant decrease in abstinence (AOR 0.81, 95% CI 0.65–1.01, P = 0.07), which was offset by a substantial increase in 100% condom use (AOR 1.54, 95% CI 1.07–2.20, P = 0.02). Numbers of sex partners and frequency of sex were similar before versus after starting ART. A trend for decreased sexually transmitted infections following ART initiation provides additional support for the validity of the self-reported behavioral outcomes (AOR 0.67, 95% CI 0.44–1.02, P = 0.06). Conclusion:In the setting of ongoing risk reduction education and provision of free condoms, initiation of ART was not associated with increased sexual risk behavior in this cohort of Kenyan FSWs.

Antiretroviral Adherence and Development of Drug Resistance Are the Strongest Predictors of Genital HIV-1 Shedding among Women Initiating Treatment

Persistent genital human immunodeficiency virus type 1 (HIV-1) shedding among women receiving antiretroviral therapy (ART) may present a transmission risk. We investigated the associations between genital HIV-1 suppression after ART initiation and adherence, resistance, pretreatment CD4 cell count, and hormonal contraceptive use. First-line ART was initiated in 102 women. Plasma and genital HIV-1 RNA levels were measured at months 0, 3, and 6. Adherence was a strong and consistent predictor of genital HIV-1 suppression (P < .001), whereas genotypic resistance was associated with higher vaginal HIV-1 RNA level at month 6 (P = .04). These results emphasize the importance of adherence to optimize the potential benefits of ART for reducing HIV-1 transmission risk.

A Prospective Study of Risk Factors for Bacterial Vaginosis in HIV-1-Seronegative African Women

Background: Bacterial vaginosis (BV) is common and has been associated with increased HIV-1 susceptibility. The objective of this study was to identify risk factors for BV in African women at high risk for acquiring HIV-1. Methods: We conducted a prospective study among 151 HIV-1-seronegative Kenyan female sex workers. Nonpregnant women were eligible if they did not have symptoms of abnormal vaginal itching or discharge at the time of enrollment. At monthly follow-up, a vaginal examination and laboratory testing for genital tract infections were performed. Multivariate Andersen-Gill proportional hazards analysis was used to identify correlates of BV. Results: Participants completed a median of 378 (interquartile range 350–412) days of follow-up. Compared with women reporting no vaginal washing, those who reported vaginal washing 1 to 14 [adjusted hazard ratio (aHR) 1.29, 95% confidence interval (CI) 0.88–1.89], 15 to 28 (aHR 1.60, 95% CI 0.98–2.61), and >28 times/wk (aHR 2.39, 95% CI 1.35–4.23) were at increased risk of BV. Higher BV incidence was also associated with the use of cloth for intravaginal cleansing (aHR 1.48, 95% CI 1.06–2.08) and with recent unprotected intercourse (aHR 1.75, 95% CI 1.47–2.08). Women using depot medroxyprogesterone acetate contraception were at lower risk for BV (aHR 0.59, 95% CI 0.48–0.73). Conclusions: Vaginal washing and unprotected intercourse were associated with increased risk of BV. These findings could help to inform the development of novel vaginal health approaches for HIV-1 risk reduction in women.

Effect of Acquisition and Treatment of Cervical Infections on HIV-1 Shedding in Women on Antiretroviral Therapy

Background:Cervicitis increases the quantity of HIV-1 RNA in cervical secretions when women are not taking antiretroviral therapy (ART), and successful treatment of cervicitis reduces HIV-1 shedding in this setting. Objective:To determine the effect of acquisition and treatment of cervical infections on genital HIV-1 shedding in women receiving ART. Design:Prospective cohort study. Methods:We followed 147 women on ART monthly for incident nonspecific cervicitis, gonorrhea, and chlamydia. Cervical swabs for HIV-1 RNA quantitation were collected at every visit. The lower limit for linear quantitation was 100 copies per swab. We compared the prevalence of HIV-1 RNA detection before (baseline) versus during and after treatment of cervical infections. Results:Thirty women contributed a total of 31 successfully treated episodes of nonspecific cervicitis (N = 13), gonorrhea (N = 17), and chlamydia (N = 1). HIV-1 RNA was detected in cervical secretions before, during, and after cervicitis at one (3.2%), five (16.1%), and three (9.7%) visits, respectively. Compared with baseline, detection of HIV-1 RNA was increased when cervical infections were present (adjusted odds ratio 5.7, 95% confidence interval 1.0–30.3, P = 0.04). However, even in the subset of women with cervical HIV-1 RNA levels above the threshold for quantitation, most had low concentrations during cervical infections (median 115, range 100–820 copies per swab). Conclusion:Although these data show a statistically significant increase in cervical HIV-1 RNA detection when cervical infections are present, most cervical HIV-1 RNA concentrations were near the threshold for detection, suggesting that infectivity remains low. Antiretroviral therapy appears to limit increases in genital HIV-1 shedding caused by cervical infections.

Changes in the contribution of genital tract infections to HIV acquisition among Kenyan high-risk women from 1993 to 2012.

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.

A prospective cohort study comparing the effect of single-dose 2 G metronidazole on trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women

Background This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women. Methods Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed as having TV by saline microscopy were treated with single-dose 2 g oral metronidazole. All women on antiretroviral therapy (ART) used nevirapine-based regimens. Generalized estimating equations with a logit link were used to compare the frequency of persistent TV (defined as the presence of motile trichomonads by saline microscopy at the next examination visit within 60 days) by HIV status. Results Three-hundred sixty participants contributed 570 infections to the analysis (282 HIV-seropositive and 288 HIV-seronegative). There were 42 (15%) persistent infections among HIV-seropositive participants versus 35 (12%) among HIV-seronegative participants (adjusted odds ratio, 1.14; 95% confidence interval [CI], 0.70–1.87). Persistent TV was highest among HIV-seropositive women using ART (21/64 [33%]) compared with HIV-seropositive women not using ART (21/217 [10%]). Concurrent bacterial vaginosis (BV) at TV diagnosis was associated with an increased likelihood of persistent TV (adjusted odds ratio, 1.90; 95% confidence interval, 1.16–3.09). Conclusions The frequency of persistent TV infection after treatment with single-dose 2 g oral metronidazole was similar by HIV status. Alternative regimens including multiday antibiotic treatment may be necessary to improve cure rates for women using nevirapine-based ART and women with TV and concurrent BV.

Prevalence, clinical and virologic outcomes of hepatitis B virus co-infection in HIV-1 positive Kenyan women on antiretroviral therapy.

Background Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART. Methods In this prospective cohort study, HIV-1 seropositive women initiated three-drug ART regimens that included lamivudine as the single drug active against HBV. Archived samples were tested for HBsAg, with further testing to determine HBeAg seroprevalence, HBV DNA suppression, and lamivudine resistance. We estimated the prevalence of chronic HBV and examined associations between HBV co-infection and clinical and virologic outcomes with chi-square tests, logistic regression, Kaplan-Meier and Cox regression. Results In a cohort of 159 women followed for a median of 3.4 years (interquartile range 1.4–4.5), 11 (6.9%; 95% CI 3.1–10.7) had chronic HBV infection. Of these, 9 (82%) achieved undetectable plasma HBV DNA levels. One woman developed lamivudine resistance, for an incidence of 3 per 100 person-years. The HBV co-infected women were at greater risk for abnormal ALT elevations compared to HIV-1 mono-infected women (HR 2.37; 95% CI 1.1–5.3). There were no differences between HBV-infected and uninfected women in mortality, CD4 count, or HIV-1 RNA suppression. Conclusion The prevalence of chronic HBV in this cohort was similar to recent studies from other African populations. Given our long-term follow-up, lamivudine resistance was lower than expected for HIV-1/HBV co-infected patients. Improved screening for HBV and extended follow-up of HIV-1/HBV co-infected individuals are needed to better understand the impact of different ART regimens on clinical outcomes in this population.

Changes in vaginal microbiota and immune mediators in HIV-1-seronegative Kenyan women initiating depot medroxyprogesterone acetate

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.

A pilot study of the feasibility of a vaginal washing cessation intervention among Kenyan female sex workers

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 womens 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 Nugents 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.

Incidence and correlates of Chlamydia trachomatis infection in a high-risk cohort of Kenyan women.

Background In Africa, data on Chlamydia trachomatis infection are scarce because reliable diagnosis is costly and not widely available. Our objective was to evaluate the incidence and correlates of C. trachomatis infection among high-risk Kenyan women. Methods We conducted prospective cohort analyses using data from a cohort of women who reported transactional sex. C. trachomatis testing was performed using the Gen-Probe Aptima GC/CT Detection System. We used Andersen-Gill proportional hazards modeling to evaluate correlates of C. trachomatis. Results Between August 2006 and December 2010, 865 women contributed 2011 person-years of observation. Sixty-four women experienced 101 episodes of C. trachomatis infection (incidence rate, 5.0/100 person-years). There was a large difference in incidence by age group: those younger than 25 years had an incidence of 27.6 per 100 person-years (95% confidence interval [CI], 16.3–46.5), those 25 to 34 years old had an incidence of 8.4 per 100 person-years (95% CI, 6.4–11.0), and those 35 years and older had an incidence of 2.6 per 100 person-years (95% CI, 1.8–3.6). In multivariate analyses, younger age (<25 and 25–34 years vs. ≥35 years; hazard ratio [HR], 8.5 [95% CI, 4.1–17.7] and 2.9 [95% CI, 1.7–5.0], respectively), depot medroxyprogesterone acetate use (HR, 1.8; 95% CI, 1.1–3.0), and recent Neisseria gonorrhoeae infection (HR, 3.3; 95% CI, 1.5–7.4) were significantly associated with increased risk of acquiring C. trachomatis infection. Conclusions The high incidence of C. trachomatis among younger high-risk women suggests the need for screening as an important public health intervention for this population.