Ruth Gitau

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.

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.

A prospective study of vaginal trichomoniasis and HIV-1 shedding in women on antiretroviral therapy

BackgroundTrichomonas vaginalis has been associated with increased vaginal HIV-1 RNA shedding in antiretroviral therapy (ART)-naïve women. The effect of trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been characterized. We tested the hypothesis that T. vaginalis infection would increase vaginal HIV-1 RNA shedding in women on ART, and that successful treatment would reduce vaginal HIV-1 RNA levels.MethodsWe conducted a prospective cohort study including monthly follow-up of 147 women receiving ART in Mombasa, Kenya. Those with T. vaginalis infection, defined by the presence of motile trichomonads on vaginal saline wet mount, received treatment with single dose metronidazole (2 g). Test of cure was performed at the next monthly visit. Using the pre-infection visit as the reference category, we compared detection of vaginal HIV-1 RNA before versus during and after infection using generalized estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the lower limit for linear quantitation.ResultsAmong 31 women treated for trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for quantitation before, during, and after T. vaginalis infection in 4 (13% [95% CI 4% - 30%]), 4 (13% [95% CI 4% - 30%]), and 5 (16% [95% confidence interval {CI} 5% - 34%]) women respectively. After adjusting for potential confounding factors, we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p = 0.7). In addition, detection of HIV-1 RNA was similar before infection versus after successful treatment (OR 0.68, 95% CI (0.13 - 3.45), p = 0.6).ConclusionDetection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after T. vaginalis infection.

Increased risk of genital ulcer disease in women during the first month after initiating antiretroviral therapy.

Introduction:Genital ulcer disease (GUD) is common in HIV-1-infected women, and a small number of studies have suggested increased GUD risk after antiretroviral therapy (ART) initiation. To better define this risk, we monitored 134 women at ART initiation and monthly thereafter. Methods:Women were evaluated monthly for genital ulcers. Syphilis serology was tested quarterly, and chancroid culture was performed on ulcers that were felt to be clinically consistent with a diagnosis of chancroid. A logistic model with generalized estimating equations was used to analyze predictors of GUD from baseline until 6 months after ART initiation. Results:During the study period, GUD occurred in 54 women (40.3%) at 85 visits (10.0%). GUD prevalence was 9.7% at baseline, increased to 16.7% at month 1 [adjusted odds ratio (aOR) 1.9 (1.0-3.6), P = 0.04], then decreased to 6.4% by month 6. History of GUD [aOR 3.8 (1.9-7.7), P < 0.001) and CD4 count <100 [aOR 1.8 (1.0-3.4), P = 0.06] were associated with increased risk of GUD after ART initiation. Discussion:Women experience increased risk of GUD in the first month after ART initiation, particularly if they have low CD4 counts or a history of GUD.

The posttrial effect of oral periodic presumptive treatment for vaginal infections on the incidence of bacterial vaginosis and Lactobacillus colonization.

Background: We previously demonstrated a decrease in bacterial vaginosis (BV) and an increase in Lactobacillus colonization among randomized controlled trial (RCT) participants who received monthly oral periodic presumptive treatment (PPT; 2 g metronidazole + 150 mg fluconazole). Posttrial data were analyzed to test the hypothesis that the treatment effect would persist after completion of 1 year of PPT. Methods: Data were obtained from women who completed all 12 RCT visits and attended ≥1 posttrial visit within 120 days after completion of the RCT. We used Andersen-Gill proportional hazards models to estimate the posttrial effect of the intervention on the incidence of BV by Gram stain and detection of Lactobacillus species by culture. Results: The analysis included 165 subjects (83 active and 82 placebo). The posttrial incidence of BV was 260 per 100 person-years in the intervention arm versus 358 per 100 person-years in the placebo arm (hazard ratio = 0.76; 95% confidence interval, 0.51–1.12). The posttrial incidence of Lactobacillus colonization was 180 per 100 person-years in the intervention arm versus 127 per 100 person-years in the placebo arm (hazard ratio = 1.42; 95% confidence interval, 0.85–2.71). Conclusions: Despite a decrease in BV and an increase in Lactobacillus colonization during the RCT, the effect of PPT was not sustained at the same level after cessation of the intervention. New interventions that reduce BV recurrence and promote Lactobacillus colonization without the need for ongoing treatment are needed.

Genital ulceration does not increase HIV-1 shedding in cervical or vaginal secretions of women taking antiretroviral therapy.

Objectives Genital ulcer disease (GUD) is associated with increased HIV-1-RNA shedding in antiretroviral therapy (ART)-naive women. The effect of GUD on HIV-1 shedding among ART-treated women is not known. The objective of this study was to test the hypothesis that genital ulcerations increase genital HIV-1-RNA shedding in women receiving ART. Methods Eligible women initiated ART and attended monthly visits with inspection for genital lesions and collection of genital swabs. GUD cases diagnosed after 2 months or more on ART were included for analysis and served as their own controls. HIV-1 RNA was quantitated in specimens collected before, during and after GUD for all cases. The lower limit of quantitation was 100 HIV-1-RNA copies/swab. Using the pre-GUD visit as the reference, the detection of genital HIV-1 RNA before versus during and after GUD episodes was compared. Results 36 women had GUD episodes after ART initiation. HIV-1 RNA was detected before, during and after GUD in cervical secretions from four (11%), one (3%) and six (17%) women, respectively, and in vaginal secretions from three (8%), four (11%) and four (11%) women, respectively. After adjustment for time on ART, there was no difference in the detection of cervical HIV-1 RNA before versus during GUD (adjusted OR 0.22, 95% CI 0.04 to 1.23). Likewise, GUD did not increase HIV-1 detection in vaginal secretions (adjusted OR 1.32, 95% CI 0.29 to 5.92). Conclusions GUD did not significantly increase cervical or vaginal HIV-1 shedding. The results suggest that ART maintains its effectiveness for genital HIV-1 suppression despite GUD episodes.

The post-trial effect of oral periodic presumptive treatment for vaginal infections on the incidence of bacterial vaginosis and Lactobacillus colonization

Background Bacterial vaginosis (BV) is a highly prevalent infection that frequently recurs following standard treatment. In a randomised controlled trial (RCT) of oral periodic presumptive treatment (PPT) to reduce vaginal infections among Kenyan women, we observed a decrease in BV and an increase in Lactobacillus colonisation among women randomised to receive 2 g metronidazole +150 mg fluconazole monthly for 12 months. After the trial, women were invited to continue follow-up in an open cohort study. These post-trial data were analysed to test the hypothesis that the treatment effect would persist in the absence of PPT. Methods Data were obtained from women who completed all 12 RCT visits and attended ≥1 cohort study visit within 120 days of their final RCT visit. We used Andersen-Gill proportional hazards models to estimate the post-trial effect of the intervention vs placebo on the incidence of BV by Gram stain (Nugent score ≥7) and Lactobacillus species by culture on Rogosa agar. Results The RCT enrolled 310 subjects (155 per arm), of whom 165 (83 active and 82 placebo) were included in this analysis. Included subjects were slightly older (median (IQR): 33 years (29–39) vs 30 years (26–35); p<0.001) and reported a longer duration of sex work (median (IQR): 6 years (2–11) vs 3 years (1–6); p<0.001) compared to those excluded. At the final RCT visit, which represented the baseline visit for this analysis, demographic and behavioural characteristics were similar by arm. The prevalence of BV at the final RCT visit was 16% in the active arm and 43% in the placebo arm (p<0.001). The post-trial incidence of BV was 260/100 person-years (p-yrs) in the active arm vs 358/100 p-yrs in the placebo arm (HR=0.76; 95% CI: 0.51% to 1.12%). The prevalence of Lactobacillus colonisation at the final RCT visit was 17% in the active arm and 18% in the placebo arm (p=0.81). The post-trial incidence of Lactobacillus colonisation was 180/100 p-yrs in the active arm vs 127/100 p-yrs in the placebo arm (HR=1.42; 95% CI: 0.85% to 2.71%). Conclusions Despite a decrease in BV and an increase in Lactobacillus colonisation during the RCT, the effect of PPT was not sustained during the 120 days following cessation of the intervention. New interventions that reduce BV recurrence and promote long-term Lactobacillus colonisation without the need for ongoing PPT or suppressive therapy are needed.

P2-S2.13 A pilot study of the effectiveness of a vaginal washing cessation intervention among Kenyan female sex workers

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 womens 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 Nugents 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.