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Background Timely diagnosis of infant HIV infection is essential for antiretroviral therapy (ART) initiation. In a randomized controlled trial, we found the Texting Improves Testing (TextIT) intervention (a theory-based text messaging system) to be efficacious for improving infant HIV testing rates and maternal retention in prevention of mother-to-child HIV transmission (PMTCT) programs. Using an implementation science approach, we aimed to evaluate real-world effectiveness of the intervention. Methods and findings In a pragmatic, cluster-randomized, stepped-wedge trial with 2 time periods of observation, we randomly allocated 10 clinics to begin implementing the intervention immediately and 10 clinics to begin implementing 6 months later. To approximate real-world conditions, inclusion criteria were broad. Women at clinics implementing the intervention received up to 14 text messages during pregnancy and after delivery and had the option to respond to text messages, call, or send inquiry text messages to a designated clinic phone. The primary outcomes were infant HIV testing and maternal retention in care during the first 8 weeks after delivery. We used modified Poisson regression with robust variance estimation to estimate the relative risk and 95% confidence intervals (CIs). Generalized estimating equations were applied on individual-level data to account for clustering by site. Between February 2015 and December 2016, 4,681 women were assessed for study participation, and 2,515 were included. Participant characteristics at enrollment did not differ by study arm. Overall median age was 27 years (interquartile range [IQR] 23–30), median gestational age was 30 weeks (IQR 28–34), 99% were receiving ART, and 87% who enrolled during intervention phases owned a phone. Of 2,326 infants analyzed, 1,466 of 1,613 (90.9%) in the intervention group and 609 of 713 (85.4%) in the control group met the primary outcome of HIV virologic testing performed before 8 weeks after birth (adjusted relative risk [aRR] 1.03; 95% CI 0.97–1.10; P = 0.3). Of 2,472 women analyzed, 1,548 of 1,725 (90%) in the intervention group and 571 of 747 (76%) in the control group met the primary outcome of retention in care during the first 8 weeks after delivery (aRR 1.12; 95% CI 0.97–1.30; P = 0.1). This study had two main limitations. Staff at all facilities were aware of ongoing observation, which may have contributed to increased rates of infant HIV testing and maternal retention in care at both intervention and control facilities, and programmatic initiatives to improve maternal and infant retention in care were ongoing at all facilities at the time of this study, which likely limited the ability to demonstrate effectiveness of the trial intervention. Conclusions In this study, a larger proportion of infants in the intervention group received HIV testing compared with the control group, but the difference was small and not statistically significant. There was also a nonsignificant increase in maternal postpartum retention in the intervention periods. Despite the lack of a significant effect of the intervention, key lessons emerged, both for strengthening PMTCT and for implementation research in general. Perhaps most important, improving the implementation of usual care may have been sufficient to substantially improve infant HIV testing rates. Trial registration ClinicalTrials.gov Trial Number NCT02350140., In a study in Kenya, Thomas Odeny and co-workers investigate the value of text reminders for infant HIV testing and retaining mothers in care., Author summary Why was this study done? Low retention of mother–infant pairs in postpartum HIV care poses a major threat to successful elimination of mother-to-child HIV transmission in sub-Saharan Africa. The increase in the number of mobile phone connections in sub-Saharan Africa has been spectacular, presenting a unique opportunity to add mobile technology for health (mHealth) to the armamentarium for turning the tide of HIV. We developed the Texting Improves Testing (TextIT) intervention to improve uptake of infant HIV testing and maternal retention in postpartum HIV care in a high–HIV-burden setting. Text messages were designed using behavioral theory. Women received up to 14 text messages during pregnancy and after delivery. Messages were tailored based on recipient’s gestational age, name, preferred time, desired language (English, Kiswahili, or Dholuo), date of delivery, and infant’s name. Participants had the option to respond to text messages, call, or send inquiry text messages. In a randomized controlled efficacy trial, we found that the TextIT intervention significantly improved rates of infant HIV testing and maternal retention in postpartum HIV care. To achieve policy change leading to broader implementation of this evidence-based intervention, we sought to provide evidence of effectiveness under real-world routine care conditions. What did the researchers do and find? Using an implementation science approach, we designed a cluster randomized, stepped-wedge trial with 2 time periods of observation. We randomly allocated 10 health facilities to begin implementing the intervention immediately, while the remaining 10 began implementing approximately 6 months later. Consistent with real-world implementation conditions, inclusion criteria were minimal. Women were offered the opportunity to receive text messages if they were ≥18 years old or emancipated minors and between 28 weeks’ gestation and delivery. We found that 1,466 of 1,613 (90.9%) infants in the intervention group underwent HIV testing within 8 weeks after birth compared to 609 of 713 (85.4%) in the control group. We also found that 1,548 of 1,725 (90%) women in the intervention group were retained in care during the first 8 weeks after delivery compared to 571 of 747 (76%) in the control group. What do these findings mean? We observed nonsignificant increases in infant HIV testing and maternal retention in postpartum care associated with short message service (SMS) text messaging. Nevertheless, HIV testing of >90% aligns with the global target of diagnosing >90% of all children living with HIV. Recognizing that strict adherence to statistical thresholds in implementation research may not provide optimal guidance for public health practice, interpretation of estimates of improvement in such studies should be contextualized in terms of the costs and benefits of implementing at scale.

Suppressive therapy and periodic presumptive treatment (PPT) are distinct but related strategies that have been used to reduce the incidence of bacterial vaginosis (BV). Here, we review clinical trial evidence of the effectiveness of suppressive therapy and PPT to reduce BV, and discuss their roles for women who frequently experience symptomatic or asymptomatic BV. Among women who were recently and successfully treated for symptomatic BV, suppressive therapy with twice-weekly metronidazole gel for 16 weeks reduces the likelihood of recurrent symptomatic BV and is currently recommended by the Centers for Disease Control and Prevention for prevention of recurrent BV. The premise of PPT is to provide regimens used to treat BV at regular intervals to reduce the overall frequency of BV, regardless of symptoms. Three PPT trials were conducted using different routes (oral or intravaginal), doses, and frequencies of administration. Each trial demonstrated a significant reduction in BV over the course 12 months, ranging from a 10 to 45% decrease. PPT regimens that substantially reduce the frequency of BV over time could be evaluated in clinical trials to assess whether a reduced frequency of BV leads to subsequent reductions in BV-associated sequelae. While both suppressive therapy and PPT reduce BV, their impact wanes following cessation of the regimen. Given the high prevalence of BV globally and burden of adverse reproductive health outcomes among women with BV, there is a critical need for more effective treatments that produce durable shifts in the microbiota towards vaginal health.

A recent study of HIV serodiscordant couples found that depot medroxyprogesterone acetate (DMPA) and oral contraceptive pills (OCPs) were associated with increased HIV risk in the presence, but not in the absence, of bacterial vaginosis. We assessed whether bacterial vaginosis is an effect modifier of the association between hormonal contraception and HIV seroconversion in female sex workers (FSWs) in Mombasa, Kenya.Prospective cohort study.Data collected from HIV-negative FSWs from 1993 to 2017 were analyzed. Cox proportional hazards models were used to assess the relationship between HIV seroconversion and use of DMPA, OCPs, or hormonal contraceptive implants (Norplant, Jadelle).A total of 1985 women contributed 7127 person-years of follow-up; 307 women seroconverted to HIV (4.32/100 person-years). DMPA was significantly associated with elevated risk of HIV seroconversion in women with [aHR 1.56, 95% confidence interval (CI) 1.08-2.25; P = 0.02] and without (aHR 2.08, 95% CI 1.46-2.97; P 0.001) bacterial vaginosis (interaction P = 0.4). Similarly, OCP use was associated with increased HIV risk both in the presence (aHR 1.50, 95% CI 0.94-2.39; P = 0.09) and absence (aHR 1.61, 95% CI 0.99-2.64; P = 0.06) of bacterial vaginosis (interaction P = 0.9), though neither stratum reached statistical significance. Implants were not associated with HIV seroconversion overall (aHR 0.99, 95% CI 0.40-2.45; P = 0.9), or in women with (aHR 0.65, 95% CI 0.16-2.72; P = 0.6) and without (aHR 1.39, 95% CI 0.43-4.46; P = 0.6) bacterial vaginosis (interaction P = 0.5).Bacterial vaginosis had no effect on the associations between hormonal contraceptives and HIV seroconversion in this cohort. Contraceptive implants were not associated with increased HIV risk compared with no contraception.

Background Phenotypic fluoroquinolone resistance was first reported in Western Kenya in 2009 and later in Coastal Kenya and Nairobi. Until recently gonococcal fluoroquinolone resistance mechanisms in Kenya had not been elucidated. The aim of this paper is to analyze mutations in both gyrA and parC responsible for elevated fluoroquinolone Minimum Inhibitory Concentrations (MICs) in Neisseria gonorrhoeae (GC) isolated from heterosexual individuals from different locations in Kenya between 2013 and 2017. Methods Antimicrobial Susceptibility Tests were done on 84 GC in an ongoing Sexually Transmitted Infections (STI) surveillance program. Of the 84 isolates, 22 resistant to two or more classes of antimicrobials were chosen for analysis. Antimicrobial susceptibility tests were done using E-test (BioMerieux) and the results were interpreted with reference to European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. The isolates were sub-cultured, and whole genomes were sequenced using Illumina platform. Reads were assembled de novo using Velvet, and mutations in the GC Quinolone Resistant Determining Regions identified using Bioedit sequence alignment editor. Single Nucleotide Polymorphism based phylogeny was inferred using RaxML. Results Double GyrA amino acid substitutions; S91F and D95G/D95A were identified in 20 isolates. Of these 20 isolates, 14 had an additional E91G ParC substitution and significantly higher ciprofloxacin MICs (p = 0.0044*). On the contrary, norfloxacin MICs of isolates expressing both GyrA and ParC QRDR amino acid changes were not significantly high (p = 0.82) compared to MICs of isolates expressing GyrA substitutions alone. No single GyrA substitution was found in the analyzed isolates, and no isolate contained a ParC substitution without the simultaneous presence of double GyrA substitutions. Maximum likelihood tree clustered the 22 isolates into 6 distinct clades. Conclusion Simultaneous presence of amino acid substitutions in ParC and GyrA has been reported to increase gonococcal fluoroquinolone resistance from different regions in the world. Our findings indicate that GyrA S91F, D95G/D95A and ParC E91G amino acid substitutions mediate high fluoroquinolone resistance in the analyzed Kenyan GC.

BackgroundWhile bacterial vaginosis has been associated with an increased risk of Trichomonas vaginalis (TV) acquisition, it is unknown whether other characteristics of the vaginal microbiota, including the presence of key bacterial species, influence a woman’s risk of TV acquisition.MethodsThe vaginal microbiota before 25 unique episodes of TV infection involving 18 women was compared to that of 50 controls who remained uninfected. TV was detected by transcription-mediated amplification. Vaginal microbiota were quantified using broad-range polymerase chain reaction analysis and taxon-specific quantitative PCR of the 16S ribosomal RNA gene.ResultsTV acquisition was significantly associated with the presence of Prevotella amnii (risk ratio [RR], 2.21; 95% confidence interval [CI], 1.12–4.38; P = .02) and Sneathia sanguinegens (RR, 2.58; 95% CI, 1.00–6.62; P = .049). When adjusted for menstrual phase, the association between P. amnii and TV acquisition remained similar (adjusted RR, 2.11; 95% CI, 1.03–4.33; P = .04), but the association between S. sanguinegens and TV acquisition was attenuated (adjusted RR, 2.31; 95% CI, .86–6.23; P = .10).ConclusionsKey vaginal bacterial species may contribute to the susceptibility to TV acquisition. Understanding how these bacterial species increase a woman’s risk of TV acquisition could help to guide the development of novel strategies to reduce women’s risk of TV infection.

ObjectivesFemale sex workers (FSWs) in sub-Saharan Africa are a key population for HIV prevention and treatment interventions, but less attention is given to their family planning needs. We evaluated the prevalence and predictors of unmet contraceptive need in HIV-positive FSWs.Study designThis cross-sectional analysis used data from an existing longitudinal study of FSWs in Mombasa, Kenya. This analysis included women who were HIV positive, age ≥18 years, pre-menopausal, not currently pregnant or desiring pregnancy, and reported exchanging sex for cash or in-kind payment at the time of enrollment. Unmet contraceptive need was defined as non-use of modern non-barrier contraceptives and not currently trying to become pregnant. Poisson regression was used to identify factors independently associated with unmet contraceptive need.ResultsAmong 346 HIV-positive FSWs, 125 (36.1%) reported modern non-barrier contraceptive use, leaving 221 (63.9%, 95%CI 58.8-68.9%) with unmet contraceptive need. Condom use was the only form of contraception for 129 (37.3%) participants. In unadjusted analyses, unmet contraceptive need was associated with physical abuse in the past year by someone other than a regular partner (PR 1.2, 95%CI 1.0-1.5), desire for (more) children (PR 1.3, 95%CI 1.1-1.5), and having 2-3 previous pregnancies compared to 0-1 prior pregnancies (PR 0.8, 95%CI 0.6-0.9). In adjusted analyses, lower number of previous pregnancies and having desire for future children remained significantly associated with a higher prevalence of unmet contraceptive need.ConclusionsUnmet need for modern non-barrier contraception was found in two-thirds of HIV-positive FSWs who reported that they were not currently trying to become pregnant, and was higher in women with the lowest number of prior pregnancies (0-1 prior pregnancies) and in those reporting desire for (more) children in the future. These findings highlight the need for concerted efforts to identify and eliminate barriers to contraceptive use in FSWs living with HIV.

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.

Objectives Self-collection of genital specimens for high-risk types of human papillomavirus (hrHPV) detection may increase cervical cancer screening uptake. We hypothesized that women would prefer self-collection to clinician-collection of genital specimens. To test this hypothesis, and women’s preference between two different self-collection approaches, a total of 199 women were enrolled in a cross-sectional study in Mombasa, Kenya. Materials and methods Participants provided self-collected specimens using the Evalyn cytobrush (Rovers) stored in a dry tube and the Viba cytobrush (Rovers) stored in wet Aptima media (Hologic). A clinician also collected cervical specimens for hrHPV testing and for cytology, and performed visual inspection using acetic acid. A post-examination questionnaire assessed preferences for the different methods of specimen collection. To test the difference in proportions for each collection method, we performed an exact binomial probability test, under the null hypothesis that women would prefer each specimen-collection method equally. Results Most women preferred clinician-collection over self-collection (68% versus 32%, p

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 Studies of alcohol use and sexual behavior in African populations have primarily been cross-sectional, used nonvalidated measures of alcohol use, or relied on self-reported sexual risk endpoints. Few have focused on human immunodeficiency virus (HIV)-positive women. METHODS Longitudinal data were collected from a cohort of HIV-positive Kenyan female sex workers. At enrollment and annual visits, participants were asked about past-year alcohol use using the Alcohol Use Disorders Identification Test (AUDIT). The primary endpoint was detection of prostate-specific antigen (PSA) in vaginal secretions at quarterly examinations. Associations between hazardous/harmful alcohol use (AUDIT score ≥7), PSA detection, and secondary measures of sexual risk were evaluated using generalized estimating equations with a log binomial regression model. RESULTS A total of 405 women contributed 2750 vaginal samples over 606 person-years of follow-up. Hazardous/harmful alcohol use was reported at 16.6% of AUDIT assessments and was associated with higher risk of PSA detection (relative risk 1.50; 95% confidence interval, 1.11-2.01) relative to no alcohol use. This association was attenuated and no longer statistically significant, after adjusting for age, work venue, intimate partner violence, depression, and partnership status (adjusted relative risk, 1.13; 95% confidence interval, 0.82-1.56). In exploratory analyses, alcohol use was associated with self-report of unprotected sex and with sexually transmitted infection acquisition. CONCLUSIONS Although hazardous/harmful alcohol use was not associated with detection of PSA in adjusted analysis, associations with secondary outcomes suggest that alcohol use is at least a marker of sexual risk behavior.

Limited research exists about condom failure as experienced by female sex workers. We conducted a qualitative study to examine how female sex workers in Mombasa, Kenya contextualise and explain the occurrence of condom failure. In-depth, semi-structured interviews were conducted with thirty female sex workers to ascertain their condom failure experiences. We qualitatively analysed interview transcripts to determine how the women mitigate risk and cope with condom failure. Condom failure was not uncommon, but women mitigated the risk by learning about correct use, and by supplying and applying condoms themselves. Many female sex workers felt that men intentionally rupture condoms. Few women were aware of or felt empowered to prevent HIV, STIs, and pregnancy after condom failure. Interventions to equip female sex workers with strategies for minimising the risk of HIV, STIs, and pregnancy in the aftermath of a condom failure should be investigated.

Objective Trichomonas vaginalis is the world9s most common curable STI and has implications for reproductive health in women. We determined incidence and correlates of T. vaginalis in an HIV-uninfected peripartum cohort. Methods Women participating in a prospective study of peripartum HIV acquisition in Western Kenya were enrolled during pregnancy and followed until 9 months post partum. T. vaginalis was assessed every 1–3 months using wet mount microscopy. Correlates of incident T. vaginalis were determined using Cox proportional hazards models. Results Among 1271 women enrolled, median age was 22 years (IQR 19–27) and gestational age was 22 weeks (IQR 18–26); most (78%) were married and had uncircumcised male partners (69%). Prevalent T. vaginalis was detected in 81 women (6%) at enrolment. Among women without T. vaginalis at enrolment, 112 had T. vaginalis detected during 1079 person-years of follow-up (10.4 per 100 person-years). After adjustment for socio-economic factors, male partner circumcision status, pregnancy status and other STIs, T. vaginalis incidence was higher during pregnancy than post partum (22.3 vs 7.7 per 100 person-years, adjusted HR (aHR) 3.68, 95% CI 1.90 to 7.15, p T. vaginalis compared with women with uncircumcised partners (aHR 0.42, 95% CI 0.23 to 0.76, p=0.004). Employed women had lower risk of incident T. vaginalis than unemployed women (aHR 0.49, 95% CI 0.31 to 0.79, p=0.003); recent STI was associated with increased T. vaginalis risk (aHR 2.97, 95% CI 1.49 to 5.94, p=0.002). Conclusions T. vaginalis was relatively common in this peripartum cohort. Male circumcision may confer benefits in preventing T. vaginalis .

We conducted a prospective cohort study to evaluate intimate partner violence (IPV) as a risk factor for detectable plasma viral load in HIV-positive female sex workers (FSWs) on antiretroviral therapy (ART) in Kenya. IPV in the past year was defined as ≥1 act of physical, sexual, or emotional violence by the index partner (i.e. boyfriend/husband). The primary outcome was detectable viral load (≥180 copies/ml). In-depth interviews and focus groups were included to contextualize results. Analyses included 195 women (570 visits). Unexpectedly, IPV was associated with significantly lower risk of detectable viral load (adjusted relative risk 0.21, 95 % CI 0.05-0.84, p-value = 0.02). Qualitative findings revealed that women valued emotional and financial support from index partners, despite IPV. IPV was not a major barrier to ART adherence. The observed association between IPV and lower risk of detectable viral load in FSWs may be due to unmeasured personal and relationship factors, warranting further research.

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 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.

Objective: To test the hypothesis that increasing community antiretroviral therapy (ART) coverage would be associated with lower HIV incidence in female sex workers (FSWs) in Mombasa District Kenya. Design: Prospective cohort study. Methods: From 1998 to 2012 HIV-negative FSWs were asked to return monthly for an interview regarding risk behavior and testing for sexually transmitted infections including HIV. We evaluated the association between community ART coverage and FSW’s risk of becoming HIV infected using Cox proportional hazards models adjusted for potential confounding factors. Results: One thousand four hundred and four FSWs contributed 4335 woman-years of follow-up with 145 acquiring HIV infection (incidence 3.35/100 woman-years). The ART rollout began in 2003. By 2012 an estimated 52% of HIV-positive individuals were receiving treatment. Community ART coverage was inversely associated with HIV incidence (adjusted hazard ratio 0.77; 95% confidence interval 0.61-0.98; P=0.03) suggesting that each 10% increase in coverage was associated with a 23% reduction in FSWs’ risk of HIV acquisition. Community ART coverage had no impact on herpes simplex virus type-2 incidence (adjusted hazard ratio 0.97; 95% confidence interval 0.79-1.20; P=0.8). Conclusion: Increasing general population ART coverage was associated with lower HIV incidence in FSWs. The association with HIV incidence but not herpes simplex virus type-2 incidence suggests that the effect of community ART coverage may be specific to HIV. Interventions such as preexposure prophylaxis and antiretroviral-containing microbicides have produced disappointing results in HIV prevention trials with FSWs. These results suggest that FSWs’ risk of acquiring HIV infection might be reduced through the indirect approach of increasing ART coverage in the community. Copyright: 2015 Wolters Kluwer Health Inc

A reservoir of HIV-infected cells that persists despite suppressive antiretroviral therapy (ART) is the source of viral rebound upon ART cessation and the major barrier to a cure. Understanding reservoir seeding dynamics will help identify the best timing for HIV cure strategies. Here we characterize reservoir seeding using longitudinal samples from before and after ART initiation in individuals who sequentially became infected with genetically distinct HIV variants (superinfected). We previously identified cases of superinfection in a cohort of Kenyan women, and the dates of both initial infection and superinfection were determined. Six women, superinfected 0.2–5.2 years after initial infection, were subsequently treated with ART 5.4–18.0 years after initial infection. We performed next-generation sequencing of HIV gag and env RNA from plasma collected during acute infection as well as every ~2 years thereafter until ART initiation, and of HIV DNA from PBMCs collected 0.9–4.8 years after viral suppression on ART. We assessed phylogenetic relationships between HIV DNA reservoir sequences and longitudinal plasma RNA sequences prior to ART, to determine proportions of initial and superinfecting variants in the reservoir. The proportions of initial and superinfection lineage variants present in the HIV DNA reservoir were most similar to the proportions present in HIV RNA immediately prior to ART initiation. Phylogenetic analysis confirmed that the majority of HIV DNA reservoir sequences had the smallest pairwise distance to RNA sequences from timepoints closest to ART initiation. Our data suggest that while reservoir cells are created throughout pre-ART infection, the majority of HIV-infected cells that persist during ART entered the reservoir near the time of ART initiation. We estimate the half-life of pre-ART DNA reservoir sequences to be ~25 months, which is shorter than estimated reservoir decay rates during suppressive ART, implying continual decay and reseeding of the reservoir up to the point of ART initiation., Author summary During HIV infection, a reservoir of long-lived latently infected cells is established that persists during antiretroviral therapy (ART) and is the source of virus replication after treatment cessation. A better understanding of when viruses enter the HIV reservoir (reservoir seeding) will aid efforts to target these long-lived HIV infected cells during their establishment. We studied women infected at two different times with two genetically distinct HIV strains (called superinfection), and assessed the genetic relationship between sequences of the HIV strains that circulated throughout infection (pre-ART HIV RNA sequences) and the HIV strains that persisted in reservoir cells (HIV DNA sequences during ART). We estimated when HIV DNA sequences entered the reservoir by identifying the time the most genetically related HIV RNA sequence was detected. In most cases we observed that viruses in the reservoir included both the initial and superinfecting lineages, suggesting reservoir seeding occurs throughout HIV infection. However, the majority of HIV sequences entered the reservoir near the time of ART initiation, suggesting that novel strategies that aim to reduce reservoir size should focus on times immediately prior to ART.

ObjectivesWe evaluated the relationship of sexually transmitted infections (STIs) and genital infections during pregnancy and subsequent risk for infant mortality and stillbirth.MethodsThis was a nested longitudinal analysis using data from a study of peripartum HIV acquisition in Kenya. In the parent study, HIV-uninfected women were enrolled during pregnancy and followed until 9 months postpartum. For this analysis, women who tested positive for HIV at any point, had a non-singleton pregnancy or a spontaneous abortion Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Syphilis was diagnosed using rapid plasma reagin testing and genital ulcer disease (GUD) identified by clinical examination. Treatment of laboratory-confirmed STIs and syndromic management was provided per Kenyan national guidelines. Predictors of stillbirth and infant mortality were determined using logistic regression and Cox proportional hazards models.ResultsOverall, among 1221 women, 55% had STIs or genital infections detected: vaginal yeast (25%), BV (22%), TV (6%), CT (5%), NG (2%) and syphilis (1%). Among women with STIs/genital infections (n=592), 34% had symptoms. Overall, 19/1221 (2%) women experienced stillbirths. Among 1202 live births, 34 infant deaths occurred (incidence 4.0 deaths per 100 person-years, 95% CI 2.8 to 5.5). After adjustment for maternal age, education and study site, stillbirth was associated with maternal GUD (adjusted OR=9.19, 95% CI1.91 to 44.35, p=0.006). Maternal NG was associated with infant mortality (adjusted HR=3.83, 95% CI1.16 to 12.68, p=0.028); there was some evidence that maternal CT was associated with infant mortality. Stillbirth or infant mortality were not associated with other genital infections.ConclusionsSTIs and genital infections were common, frequently asymptomatic and some associated with stillbirth or infant mortality. Expediting diagnosis and treatment of STIs in pregnancy may improve infant outcomes.

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.

Bacterial vaginosis, characterized by the replacement of the Lactobacillus-dominant microbiota with anaerobic bacteria and facultative Gram-negative rods, has been associated with adverse reproductive health outcomes including HIV acquisition. With the advent of newer molecular techniques, the vaginal microbiota can be investigated in more detail and the association with HIV examined more thoroughly. This review examines recent evidence suggesting that vaginal dysbiosis with increased microbial diversity, specific vaginal bacterial communities, and the presence and concentrations of some individual bacterial species, may increase HIV susceptibility. Potential mechanisms through which vaginal microbiota could impact HIV susceptibility are discussed. On the basis of the available data, this review finds that there is a modest, but growing, body of evidence linking vaginal microbiota to HIV susceptibility in women. The evidence could be strengthened through two main pathways. First, laboratory studies such as ex-vivo or animal experiments are needed to move from plausible mechanisms towards proven mechanisms that explain an effect of the vaginal microbiota on HIV susceptibility. Second, experimental evidence could directly test the hypothesis that sustaining optimal microbiota reduces HIV risk, though there are important obstacles to conducting such studies. Finally, this review examines strong evidence from a recent publication suggesting that deviations from an optimal vaginal microbiome, and particularly the presence of some bacterial communities with high relative abundance of Gardnerella vaginalis, reduces the efficacy of vaginal tenofovir-based microbicides.

Background Cervicitis is an inflammatory condition of the cervix associated with upper genital tract infection and reproductive complications. Although cervicitis can be caused by several known pathogens, the etiology frequently remains obscure. Here we investigate vaginal bacteria associated with bacterial vaginosis as potential causes of cervicitis. Methods Associations between vaginal bacteria and cervicitis were assessed in a retrospective case-control study of women attending a Seattle sexually transmitted disease clinic. Individual bacterial species were detected using 2 molecular methods: quantitative polymerase chain reaction (qPCR) and broad-range 16S rRNA gene PCR with pyrosequencing. The primary finding from this initial study was evaluated using qPCR in a second cohort of Kenyan women. Results The presence of Mageeibacillus indolicus, formerly BVAB3, in the cervix was associated with cervicitis, whereas the presence of Lactobacillus jensenii was inversely associated. Quantities of these bacteria did not differ between cervicitis cases and controls, although in a model inclusive of presence and abundance, M. indolicus remained significantly associated with cervicitis after adjustment for other cervicitis-causing pathogens. M. indolicus was not associated with cervicitis in our study of Kenyan women, possibly due to differences in the clinical definition of cervicitis. Conclusions Colonization of the endocervix with M. indolicus may contribute to the clinical manifestations of cervicitis, but further study is needed to determine whether this finding is repeatable and applicable to diverse groups of women. Colonization of the cervix with L. jensenii could be a marker of health, perhaps reducing inflammation or inhibiting pathogenic infection.

Background. Vaginal infections are common, frequently recur, and may increase women's risk for sexually transmitted infections (STIs). We tested the efficacy of a novel regimen to prevent recurrent vaginal infections. Methods. Human immunodeficiency virus (HIV)–negative women 18–45 years old with 1 or more vaginal infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or Trichomonas vaginalis (TV), were randomly assigned to receive vaginal suppositories containing metronidazole 750 mg plus miconazole 200 mg or matching placebo for 5 consecutive nights each month for 12 months. Primary endpoints, evaluated every 2 months, were BV (Gram stain) and VVC (positive wet mount and culture). Results. Participants (N = 234) were randomly assigned to the intervention (N = 118) or placebo (N = 116) arm. Two hundred seventeen (93%) women completed an end-of-study evaluation. The intervention reduced the proportion of visits with BV compared to placebo (21.2% vs 32.5%; relative risk [RR] 0.65, 95% confidence interval [CI] .48–.87). In contrast, the proportion of visits with VVC was similar in the intervention (10.4%) versus placebo (11.3%) arms (RR 0.92, 95% CI .62–1.37). Conclusions. Monthly treatment with intravaginal metronidazole plus miconazole reduced the proportion of visits with BV during 12 months of follow-up. Further study will be important to determine whether this intervention can reduce women's risk of STIs.

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.

Introduction We tested the hypothesis that vaginal microbiota influence women’s susceptibility to T. vaginalis (TV) acquisition. Methods We conducted a nested case-control study of 25 episodes of TV infection using vaginal samples collected 30–60 days prior to infection in 18 HIV-negative women and 50 incidence-density matched controls. Broad-range 16S rRNA gene PCR was used to measure total vaginal bacterial load. Deep sequencing was applied to 18 first episodes of TV infection and 36 matched controls to measure bacterial diversity (Shannon index) and species richness (Chao-1 index). Bacterium-specific quantitative PCR was performed for Lactobacillus crispatus , Prevotella amnii , Sneathia sanguinegens , Dialister species Type 2, Bacterial Vaginosis Associated Bacterium 1 (BVAB-1), and Mageeibacillus indolicus for all TV infection cases and controls. The associations between Shannon and Chao-1 indices and TV acquisition were evaluated using logistic regression. Generalised estimating equations with logit link were used to evaluate associations between TV acquisition, detection of bacterial species, and total vaginal bacterial load. Results There was no association between total vaginal bacterial load, species diversity, or richness, and likelihood of TV acquisition. Detection of S. sanguinegens (odds ratio [OR] 4.00, 95% CI 1.19–13.50) and P. amnii (OR 3.45, 95% CI 1.29–9.24) were both associated with TV acquisition. M. indolicus was also associated with TV acquisition (OR 2.47, 95% CI 0.88–6.93), although not significantly. Compared to women with none of these species, women with all three bacterial species had substantially higher likelihood of TV acquisition (none-reference category; one-OR 1.57, 95% CI 0.21–11.86; two-OR 4.50, 95% CI 0.93–21.76; three-OR 5.50, 95% CI 1.15–26.40). There was no association with the other three bacterial species. Conclusion The presence of three bacterial species commonly associated with BV may increase susceptibility to TV infection. Elimination of these bacteria could be explored as an approach to decrease women’s risk of trichomoniasis.

Summary Background Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP. Methods We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0–3 indicated healthy microbiota, 4–6 intermediate, and 7–10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota. Findings Of 1470 women (median age 33 years), 357 (24%) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0·6 per 100 person years in PrEP group and 2·5 per 100 person-years in the placebo group; efficacy 76·55% [95% CI 43·09 to 90·37]), intermediate microbiota (HIV incidence 1·8 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 62·72% [95% CI −66·59 to 91·66]), or bacterial vaginosis (HIV incidence 0·9 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 72·50% [95% CI 5·98 to 91·95]; p interaction =0·871). PrEP efficacy was not significantly different between women with detected G vaginalis or Bacteroides spp morphotypes and those without these morphotypes (efficacy 68·62% vs 76·72%; p interaction =0·652); or between those with Lactobacillus spp morphotypes and those without (70·48% vs 74·08%; p interaction =0·86). Interpretation Among African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis. Funding Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.

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.

It has been hypothesized that immune activation and inflammation may increase HIV-1 susceptibility, and that cytokines may be useful biomarkers for risk. Within a prospective cohort, we conducted a nested case-control analysis of plasma cytokine levels among women who acquired HIV-13 months after sampling, compared with 3 different control groups. We observed associations between lower interleukin (IL)-6 and IL-10 and higher IL-7 levels with HIV-1 acquisition, however, these associations were inconsistent when comparing with different control groups. Inconsistent results within our study and among previous studies suggest that reproducible findings are needed before cytokines are useful biomarkers for HIV-1 susceptibility.

Human herpesvirus-8 (HHV-8) replication in the oropharynx may play an important role in HHV-8 transmission and contribute to the development of Kaposi sarcoma (KS) in some individuals. Studies in the United States and Europe report high rates of HHV-8 DNA detection in saliva of HHV-8 infected men, but little is known about the natural history of HHV-8 among persons in sub-Saharan Africa, where prevalence of HHV-8 infection and KS is greatest. To address this gap, this study evaluated oral HHV-8 replication in a cohort of 40 HHV-8 seropositive Kenyan women. Study clinicians collected daily oral swabs from participants for up to 30 consecutive days, and swab samples were tested for HHV-8 DNA using quantitative, real-time polymerase chain reaction. HHV-8 was detected at least once in 27 (68%) participants, and the overall shedding rate was 23%. On days with HHV-8 detection, mean HHV-8 quantity was 4.5 log10 copies/ml. Among HIV-infected women, CD4 count ≥500 cells/mm3 versus

Objectives Self-collection of genital specimens for high-risk types of human papillomavirus (hrHPV) detection may increase cervical cancer screening uptake. We hypothesized that women would prefer self-collection to clinician-collection of genital specimens. To test this hypothesis, and women’s preference between two different self-collection approaches, a total of 199 women were enrolled in a cross-sectional study in Mombasa, Kenya. Materials and methods Participants provided self-collected specimens using the Evalyn cytobrush (Rovers) stored in a dry tube and the Viba cytobrush (Rovers) stored in wet Aptima media (Hologic). A clinician also collected cervical specimens for hrHPV testing and for cytology, and performed visual inspection using acetic acid. A post-examination questionnaire assessed preferences for the different methods of specimen collection. To test the difference in proportions for each collection method, we performed an exact binomial probability test, under the null hypothesis that women would prefer each specimen-collection method equally. Results Most women preferred clinician-collection over self-collection (68% versus 32%, p

Vaginal washing is a common practice associated with adverse outcomes including bacterial vaginosis (BV) and HIV infection. Prior studies have not examined the associations between vaginal washing and individual vaginal bacteria, or whether these associations are independent of the effect of vaginal washing on BV. The purpose of this study was to characterize the association between vaginal washing and the presence and concentrations of vaginal bacteria associated with optimal and sub-optimal vaginal states. The analysis utilized data from participants in the placebo arm of the Preventing Vaginal Infections trial, which enrolled HIV-uninfected women from the United States and Kenya. Detection of bacterial taxa associated with BV was compared between visits with versus without reported vaginal washing. The effect of vaginal washing on a number of vaginal bacteria differed substantially (p

ObjectiveText messages significantly improve uptake of infant HIV testing in clinical trial contexts. Women who were excluded from a randomized trial in Kenya were followed to create a comparison between women who were enrolled and did not receive the study SMS intervention and women who were screened but not enrolled.DesignParallel-cohort randomized controlled trial analysis.MethodsWe compared time to infant HIV testing between women in three groups: the Trial SMS group, the Trial Control group, and the Comparison Cohort comprised of women who were screened but not enrolled.ResultsOf the 1,115 women screened, 388 (35%) were eligible for trial enrollment, and were randomized to receive either intervention text messages (Trial SMS; N = 195) or continue usual care (Trial Control; N = 193). Among 727 women not enrolled in the study (Comparison Cohort), we obtained infant HIV testing data from clinic records for 510 (70%). The cumulative probability of infant HIV testing was highest in the Trial SMS group (92.0%; 95% CI 87.5-95.3), followed by the Trial Control group (85.1%; 95% CI 79.5-89.8), and lowest among women in the Comparison Cohort (43.4%; 95% CI 39.2-47.8).ConclusionsBoth the Trial SMS group and the Trial Control group were significantly more likely to have their infants tested for HIV compared to the Comparison Cohort, providing evidence of a "clinical trial effect." This analysis suggests that SMS interventions should be implemented as an adjunct to consistent and engaged delivery of basic health services.

BackgroundHIV-1-discordant couples that remain discordant despite repeated exposure may differ from the general population in their distribution of transmission risk factors, including low plasma viral load (PVL) in the infected partner even in the absence of antiretroviral therapy (ART).MethodsWe followed two cohorts of HIV-1-infected Kenyan women: females in discordant couples (FDC) and female sex workers (FSW). We compared the distribution of undetectable (ResultsWe evaluated 296 FDC and 220 FSW. At baseline, FDC were more likely to have undetectable (RR = 6.94, bootstrap 95% CI: 3.47, 20.81) and low PVL (RR = 3.53, bootstrap 95% CI: 2.57, 5.65) than FSW. Similarly, both repeat undetectable PVL (RR = 9.36, bootstrap 95% CI: 6.04, 10.97) and repeat low (RR = 4.99, bootstrap 95% CI: 2.33, 14.04) PVL were more likely among FDC than FSW during follow-up.DiscussionWe observed higher prevalence of viral control in FDC compared to FSW in the absence of ART, suggesting potentially higher prevalence of biological HIV resistance factors among discordant couples.

We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters.HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition.Plasma levels of angiopoietin-1 and angiopoietin-2 (ANG-1, ANG-2) and soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were tested in stored samples from pre-infection, acute infection, and two chronic infection time points. We used nonparametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4200 cells/μl, stage IV disease, or antiretroviral therapy initiation) or death.Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all postinfection periods assessed (P0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (P = 0.0001), and ANG-1 decreased in chronic infection (P = 0.0004). Among 228 participants followed over 1028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (adjusted hazard ratio 5.36, 95% confidence interval 1.99-14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels.HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 postinfection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality.

Despite having the highest prevalence of any sexually transmitted infection (STI) globally, there is a dearth of data describing Trichomonas vaginalis (TV) incidence and prevalence in the general population. The lack of basic epidemiological data is an obstacle to addressing the epidemic. Once considered a nuisance infection, the morbidities associated with TV have been increasingly recognised over the past decade, highlighting the importance of this pathogen as a public health problem. Recent developments in TV diagnostics and molecular biology have improved our understanding of TV epidemiology. Improved characterisation of the natural history of TV infection has allowed us to hypothesise possible explanations for observed variations in TV prevalence with age. Direct and indirect hormonal effects on the female genital tract provide a likely explanation for the greater burden of persistent TV infection among women compared with men. Further characterisation of the global epidemiology of TV could enhance our ability to respond to the TV epidemic.

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

Identifying sexually transmitted infections (STI) in HIV-infected individuals has potential to benefit individual and public health. There are few guidelines regarding routine STI screening in sub-Saharan African HIV programs. We determined sexual risk behavior and prevalence and correlates of STI in a national survey of large HIV treatment programs in Kenya.A mobile screening team visited 39 (95%) of the 42 largest HIV care programs in Kenya and enrolled participants using population-proportionate systematic sampling. Participants provided behavioral and clinical data. Genital and blood specimens were tested for trichomoniasis, gonorrhea, chlamydia, syphilis, and CD4 T-lymphocyte counts.Among 1661 adults, 41% reported no sexual partners in the past 3 months. Among those who reported sex in the past 3 months, 63% of women reported condom use during this encounter compared with 77% of men (P0.001). Trichomoniasis was the most common STI in women (10.9%) and men (2.8%); prevalences of gonorrhea, chlamydia, and syphilis were low (1%-2%). Among women, younger age (adjusted odds ratio [OR], 0.96 per year; 95% confidence interval [CI], 0.94-0.98) and primary school education or lower level (adjusted OR, 2.16; 95% CI, 1.37-3.40) were independently associated with trichomoniasis, whereas CD4 count, cotrimoxazole use, and reported condom use were not. Reported condom use at last sex was associated with reporting that the clinic provided condoms among both women (OR, 1.7; 95% CI, 1.17-2.35) and men (OR, 2.4; 95% CI, 1.18-4.82).Women attending Kenyan HIV care programs had a 10.9% prevalence of trichomoniasis, suggesting that screening for this infection may be useful. Condom provision at clinics may enhance secondary HIV prevention efforts.

Objectives Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. Methods We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. Results At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. Conclusion Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation.

Objectives: Genitourinary tract samples are required to investigate male HIV-1 infectivity. Because semen collection is often impractical, the acceptability, feasibility and validity of post-prostatic massage fluid/ urine (post-PMF/U) was evaluated for studying male genitourinary HIV-1 shedding. Methods: HIV-1-seropositive men were evaluated after 48 h of sexual abstinence. At each visit, a clinician performed prostatic massage, then post-PMF/U and blood were collected. Participants provided semen specimens 1 week later. An audio computer-assisted self-interview (ACASI) administered after each specimen collection evaluated acceptability, adherence to instructions and recent genitourinary symptoms. HIV-1 RNA was quantified using a real-time PCR assay. Detection and quantitation of HIV-1 RNA and stability over visits were compared for semen, post-PMF/U and blood. Results: Post-PMF/U was successfully obtained at 106 visits (64%) and semen at 136 visits (81%, p

Background: The role of homosexuality and anal sex practices in the African HIV -1 epidemic is not well described. We aimed to assess the risk factors for prevalent HIV-1 infection among men who have sex with men (MSM) to guide HIV-1 prevention efforts. Methods: Socio-behavioural characteristics, signs and symptoms of sexually transmitted diseases (STD), and serological evidence of HIV-1 were determined for 285 MSM at enrolment into a vaccine preparedness cohort study. We used multivariate logistic regression to assess risk factors for prevalent HIV-1 infection. Results: HIV-1 prevalence was 43.0% [49/114, 95% confidence interval (CI), 34‐52%] for men who reported sex with men exclusively (MSME), and 12.3% (21/171, 95% CI, 7‐17%) for men who reported sex with both men and women (MSMW). Eighty-six (75%) MSME and 69 (40%) MSMW reported recent receptive anal sex. Among 174 MSM sexually active in the last week, 44% reported no use of condoms with casual partners. In the previous 3 months, 210 MSM (74%) reported payment for sex, and most clients (93%) were local residents. Prevalent HIV-1 infection was associated with recent receptive anal sex [odds ratio (OR), 6.1; 95% CI, 2.4‐16], exclusive sex with men (OR, 6.3; 95% CI, 2.3‐17), and increasing age (OR, 1.1 per year; 95% CI, 1.04‐1.12). Only four MSM reported injecting drug use. Conclusions: The high prevalence of HIV-1 in Kenyan MSM is probably attributable to unprotected receptive anal sex. There is an urgent need for HIV-1 prevention programmes to deliver targeted risk-reduction interventions and STD services to MSM in Kenya. 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2007, 21:2513‐2520

We compared HIV-1 strains in incident and prevalent infections in a cohort of men having sex with men (MSM) and female sex workers (FSW) near Mombasa, Kenya and conducted a cross-sectional study of viral isolates from a sample of HIV-1-infected MSM and FSW in Kilifi, Coast Province, Kenya. RNA extracted from plasma of 13 MSM, 9 FSW, and one heterosexual male was amplified by nested RT-PCR and the products were directly sequenced. HIV-1 strains from 21 individuals were characterized with one or more complete genome sequences, and two were sequenced in the Nef gene. The envelope quasispecies was also studied in one individual. Among MSM, eight strains were subtype A and five were recombinant. There were two epidemiologically linked pairs of sequences; one pair was subtype A and the other pair was a complex AA2CD recombinant of identical structure. Another MSM was dually infected with DG recombinant strains of related, but nonidentical, structure. MSM also harbored AC and AD recombinant strains. The FSW harbored seven subtype A strains, an AD recombinant, and an AA2D strain related to CRF16_A2D. The one heterosexual male studied had a subtype A infection. This MSM epidemic in Kenya appears to be of local origin, harboring many strains typical of the broader Kenyan epidemic. Characteristics of a close social network were identified, with extended chains of transmission, novel recombinant strains possibly generated within the network, and a relatively high proportion of recombinant and dual infections.

Background Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication (“shedding”) at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons. Methods We quantified HHV-8 oral shedding using PCR among HHV-8 seropositive persons who collected at least 14 days of oral swabs in 22 studies on 3 continents. We excluded persons taking antivirals during sampling or any prior use of antiretrovirals in those who were HIV-infected. Results 248 participants were enrolled from the US, Peru, Cameroon, Uganda, and Kenya; 61 % were men, 58 % were HIV seropositive, and 16 % had KS. Overall, 3,123 of 10,557 samples (29.6 %) had HHV-8 detected. Quantity of virus shed was highly correlated with shedding rate, (ρ = 0.72, p

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.

This study explored perceptions of HIV following local introduction of antiretroviral therapy (ART), among 30 HIV-positive and -negative female sex workers (FSWs) and 10 male bar patrons in Mombasa, Kenya. Semi-structured interviews were analyzed qualitatively to identify determinants of sexual risk behaviors. ART was not perceived as a barrier to safer sex and in some cases led to decreased high-risk behaviors. Barriers to safer sex included economic pressure and sexual partnership types. Many women reported that negotiating condom use is more difficult in long-term partnerships. These women favored short-term partnerships to minimize risk through consistent condom use. For women living with HIV, concern about maintaining health and avoiding HIV superinfection was a strong motivator of protective behaviors. For HIV-negative women, a negative HIV test was a powerful motivator. Incorporation of context- and serostatus-specific factors (e.g., self-protection for HIV-positive women) into tailored prevention counseling may support high-risk women to reduce risk behaviors.

BACKGROUND: Few studies have examined the association between self-reported sexual risk behaviors and biologic outcomes in human immunodeficiency virus (HIV)-1-seropositive African adults. METHODS: We conducted a prospective cohort study in 898 HIV-1-seropositive women who reported engaging in transactional sex in Mombasa Kenya. Primary outcome measures included detection of sperm in genital secretions pregnancy and sexually transmitted infections. Because 3 outcomes were evaluated data are presented with odds ratios [OR] and 96.7% confidence intervals [CI] to reflect that we would reject a null hypothesis if a P-value was 1 sex partner in the past week was associated with lower likelihood of detecting sperm in genital secretions (OR: 0.74 96.7% CI: 0.56 0.98). This association became nonsignificant after adjustment for reported condom use (adjusted OR: 0.81 96.7% CI: 0.60 1.08). CONCLUSIONS: Combining behavioral and biologic outcomes which provide complementary information is advantageous for understanding sexual risk behavior in populations at risk for transmitting HIV-1. The paradoxical relationship between higher numbers of sex partners and less frequent identification of sperm in genital secretions highlights the potential importance of context-specific behavior such as condom use dependent on partner type when evaluating sexual risk behavior.

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.

Hypermutation, the introduction of excessive G-to-A substitutions by host proteins in the APOBEC family, can impair replication of the human immunodeficiency virus (HIV). Because hypermutation represents a potential antiviral strategy, it is important to determine whether greater hypermutation is associated with slower disease progression in natural infection. We examined the level of HIV-1 hypermutation among 28 antiretroviral-naive Kenyan women at two times during infection. By examining single-copy gag sequences from proviral DNA, hypermutation was detected in 16 of 28 individuals. Among individuals with any hypermutation, a median of 15% of gag sequences were hypermutated (range, 5 to 43%). However, there was no association between the level of gag hypermutation and the viral load or CD4 count. Thus, we observed no overall relationship between hypermutation and markers of disease progression among individuals with low to moderate levels of hypermutation. In addition, one individual sustained a typical viral load despite having a high level of hypermutation. This individual had 43% of gag sequences hypermutated and harbored a partially defective Vif, which was found to permit hypermutation in a peripheral blood mononuclear cell culture. Overall, our results suggest that a potential antiviral therapy based on hypermutation may need to achieve a substantially higher level of hypermutation than is naturally seen in most individuals to impair virus replication and subsequent disease progression.