Loss to follow-up as a competing risk in an observational study of HIV-1 incidence.

OBJECTIVE: Conventional survival estimates may be biased if loss to follow-up (LTF) is associated with the outcome of interest. Our goal was to assess whether the association between sexual risk behavior and HIV-1 acquisition changed after accounting for LTF with competing risks regression. METHODS: HIV-1-seronegative women who enrolled in a Kenyan sex worker cohort from 1993-2007 were followed prospectively and tested for HIV at monthly clinic visits. Our primary predictor was self-reported sexual risk behavior in the past week, analyzed as a time-dependent covariate. Outcomes included HIV-1 acquisition and LTF. We analyzed the data using Cox proportional hazards regression and competing risks regression, in which LTF was treated as a competing event. RESULTS: A total of 1,513 women contributed 4,150 person-years (py), during which 198 (13.1%) acquired HIV-1 infection (incidence, 4.5 per 100 py) and 969 (64.0%) were LTF (incidence, 23.4 per 100 py). After adjusting for potential confounders, women reporting unprotected sex with multiple partners were less likely to be lost to follow-up (adjusted sub-hazard ratio (aSHR) 0.50, 95% confidence interval (CI) 0.32-0.76, relative to no sexual activity). The risk of HIV-1 acquisition after reporting unprotected sex with multiple partners was similar with Cox regression (adjusted hazard ratio (aHR) 2.41, 95% CI 1.36-4.27) and competing risks regression (aSHR 2.47, 95% CI 1.33-4.58). CONCLUSIONS: Unprotected sex with multiple partners was associated with higher HIV-1 acquisition risk, but lower attrition. This differential attrition did not substantially bias Cox regression estimates when compared to competing risks regression results.

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

Circumcision preference among women and uncircumcised men prior to scale-up of male circumcision for HIV prevention in Kisumu, Kenya.

Following the endorsement by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) of male circumcision as an additional strategy to HIV prevention, initiatives to introduce safe, voluntary medical male circumcision (VMMC) services commenced in 2008 in several sub-Saharan African communities. Information regarding perceptions of circumcision as a method of HIV prevention, however, is largely limited to data collected before this important endorsement and the associated increase in the availability of VMMC services. To address this, we completed a community-based survey of male circumcision (MC) perceptions in the major non-circumcising community in Kenya, which is the current focus of VMMC programs in the country. Data was collected between November 2008 and April 2009, immediately before VMMC program scale-up commenced. Here we present results limited to women (n = 1088) and uncircumcised males (n = 460) to provide insight into factors contributing to the acceptability and preference for MC in those targeted by VMMC programs. Separate multivariable models examining preference for circumcision were defined for married men, unmarried men, and women. Belief in the protective effect of circumcision on HIV risk was strongly associated with preference for MC in all models. Other important factors included education, perceived improvement in sexual pleasure, and perceptions of impact on condom utilization. Identified barriers to circumcision were the belief that circumcision was not part of the local culture, the perception of a long healing period following the procedure, the lack of a specific impetus to seek out services, and the general fear of pain associated with becoming circumcised. A minority of participants expressed beliefs suggesting that behavioral risk compensation with increased MC prevalence and awareness is a possibility. This work describes the early impact of a large-scale VMMC program on beliefs and behaviors regarding MC and HIV risk. It is hoped that our findings may offer guidance into anticipating potential impacts that similar programs may observe in populations throughout Eastern Africa.

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

BACKGROUND: Trichomonas 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. METHODS: We 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. RESULTS: Among 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). CONCLUSION: Detection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after T. vaginalis infection.

Establishing and sustaining a healthy vaginal environment: analysis of data from a randomized trial of periodic presumptive treatment for vaginal infections.

Data from a randomized trial of oral periodic presumptive treatment (PPT) to reduce vaginal infections were analyzed to assess the effect of the intervention on a healthy vaginal environment (normal flora confirmed by Gram stain with no candidiasis or trichomoniasis). The incidence of a healthy vaginal environment was 608 cases per 100 person-years in the intervention arm and 454 cases per 100 person-years in the placebo arm (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.17-1.58). Sustained vaginal health (healthy vaginal environment for ≥3 consecutive visits) was also more frequent in the intervention arm (HR, 1.69; 95% CI, 1.23-2.33). PPT is effective at establishing and sustaining a healthy vaginal environment.

Acceptability of medical male circumcision among uncircumcised men in Kenya one year after the launch of the national male circumcision program.

BACKGROUND: Numerous studies have demonstrated that male circumcision (MC) reduces the incidence of the Type-1 human immunodeficiency virus (HIV) among heterosexual men by at least half. METHODS: One year after the launch of a national Voluntary Medical Male Circumcision program in Kenya, this study conducted 12 focus group discussions among uncircumcised men in Nyanza Province to assess the revealed, non-hypothetical, facilitators and barriers to the uptake of MC. RESULTS: The primary barriers to MC uptake included time away from work; culture and religion; possible adverse events; and the post-surgical abstinence period. The primary facilitators of MC uptake included hygiene; social pressure; protection against HIV and other sexually transmitted infections; and improved sexual performance and satisfaction. CONCLUSIONS: Some activities which might increase MC uptake include dispelling MC misconceptions; increasing involvement of religious leaders, women's groups, and peer mobilizers for MC promotion; and increasing the relevance of MC among men who are already practicing an HIV prevention method.

Emergence of quinolone resistance and cephalosporin MIC creep in Neisseria gonorrhoeae isolates from a cohort of young men in Kisumu, Kenya, 2002 to 2009.

We evaluated antimicrobial resistance in Neisseria gonorrhoeae isolated from men enrolled in a randomized trial of male circumcision to prevent HIV. Urethral specimens from men with discharge were cultured for N. gonorrhoeae. MICs were determined by agar dilution. Clinical and Laboratory Standards Institute (CLSI) criteria defined resistance: penicillin, tetracycline, and azithromycin MICs of ≥2.0 µg/ml; a ciprofloxacin MIC of ≥1.0 µg/ml; and a spectinomycin MIC of ≥128.0 µg/ml. Susceptibility to ceftriaxone and cefixime was shown by an MIC of ≤0.25 µg/ml. Additionally, PCR amplification identified mutations in parC and gyrA genes in selected isolates. From 2002 to 2009, 168 N. gonorrhoeae isolates were obtained from 142 men. Plasmid-mediated penicillin resistance was found in 65%, plasmid-mediated tetracycline resistance in 97%, and 11% were ciprofloxacin resistant (quinolone-resistant N. gonorrhoeae [QRNG]). QRNG appeared in November 2007, increasing from 9.5% in 2007 to 50% in 2009. Resistance was not detected for spectinomycin, cefixime, ceftriaxone, or azithromycin, but MICs of cefixime (P = 0.018), ceftriaxone (P < 0.001), and azithromycin (P = 0.097) increased over time. In a random sample of 51 men, gentamicin MICs were as follows: 4 µg/ml (n = 1), 8 µg/ml (n = 49), and 16 µg/ml (n = 1). QRNG increased rapidly and alternative regimens are required for N. gonorrhoeae treatment in this area. Amid emerging multidrug-resistant N. gonorrhoeae, antimicrobial resistance surveillance is essential for effective drug choice. High levels of plasmid-mediated resistance and increasing MICs for cephalosporins suggest that selective pressure from antibiotic use is a strong driver of resistance emergence.

Implementing voluntary medical male circumcision for HIV prevention in Nyanza Province, Kenya: lessons learned during the first year.

BACKGROUND: In 2007, the World Health Organization endorsed male circumcision as an effective HIV prevention strategy. In 2008, the Government of Kenya (GoK) launched the national voluntary medical male circumcision (VMMC) program in Nyanza Province, the geographic home to the Luo, the largest non-circumcising ethnic group in Kenya. Currently, several other African countries are in the early stages of implementing this intervention. METHODS AND RESULTS: This paper uses data from a health facility needs assessment (n = 81 facilities) and a study to evaluate the implementation of VMMC services in 16 GoK facilities (n = 2,675 VMMC clients) to describe Kenya's experience in implementing the national program. The needs assessment revealed that no health facility was prepared to offer the minimum package of services as outlined by the national guidelines, and partner organizations were called upon to fill this gap. The findings concerning human resource shortages facilitated the GoK's decision to endorse trained nurses to provide VMMCs, enabling more facilities to offer the service. Findings from the evaluation study resulted in replacing voluntary counseling and testing (VCT) with provider-initiated testing and counseling (PITC) and subsequently doubling the proportion of VMMC clients tested for HIV. CONCLUSIONS: This paper outlines how certain challenges, like human resource shortages and low HIV test rates, were addressed through national policy changes, while other challenges, like large fluctuations in demand, were addressed locally. Currently, the program requires significant support from partner organizations, but a strategic plan is under development to continue to build capacity in GoK staff and facilities. Coordination between all parties was essential and was facilitated through the formation of national, provincial, and district VMMC task forces. The lessons learned from Kenya's VMMC implementation experience are likely generalizable to other African countries.

Anal sex, vaginal practices, and HIV incidence in female sex workers in urban Kenya: implications for the development of intravaginal HIV prevention methods.

Multiple intravaginal HIV prevention methods, including microbicide gels, barriers, and intravaginal rings, are in clinical development in Africa. Development of intravaginal HIV prevention products requires an understanding of sexual behavior, sexually transmitted infection (STI), and vaginitis prevalences, and sexual and vaginal practices in potential target populations. We assessed these factors in a cohort of Kenyan female sex workers (FSW). Women who reported exchanging sex for money/gifts at least three times in the past month and who were HIV uninfected were enrolled and followed for 6 months. STI prevalence and HIV incidence were analyzed by multivariate logistic regression analysis, controlling for demographic and behavioral factors. Thirty-seven percent (74/200) reported having had anal sex. Frequency of anal sex was higher with regular and casual partners than with primary partners. Women were less likely to use condoms for anal sex than for vaginal sex with regular or casual partners. Vaginal washing was universal (100%). HIV incidence was 5.6 per 100 person-years (95% CI 1.62, 11.67). HIV incidence was not associated with any demographic or risk behavior. The relatively high rate of anal sex and universal vaginal washing may complicate both safety and efficacy evaluation of intravaginal products and should be taken into account in trial design. This FSW population had significant HIV incidence and needs continued HIV prevention interventions.

Reasons for ineligibility in phase 1 and 2A HIV vaccine clinical trials at Kenya AIDS vaccine initiative (KAVI), Kenya.

BACKGROUND: With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries--worst affected by the HIV pandemic--have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. METHODOLOGY: Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. PRINCIPAL FINDINGS: Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrollment. CONCLUSIONS: Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. TRIAL REGISTRATION: Protocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2](registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted.

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.

Widow inheritance and HIV prevalence in Bondo District, Kenya: baseline results from a prospective cohort study.

BACKGROUND: Widow Inheritance is a widespread cultural practice in sub-Saharan Africa that has been postulated as contributing to risk of HIV transmission. We present baseline results from a study designed to investigate the association between widow inheritance and HIV acquisition. METHODS AND FINDINGS: We performed a cross-sectional analysis of baseline data from a prospective cohort study to investigate if widow inheritance is a risk practice for HIV infection. Study participants were 1,987 widows who were interviewed regarding their inheritance status and sexual behavior profile and tested for HIV. Of these widows, 56.3% were inherited. HIV prevalence, at 63%, was similar among non-inherited and inherited widows. We stratified exposure status by the relationship of the widow to the inheritor and the reason for inheritance, and reexamined the HIV status of four subgroups of inherited women relative to the HIV status of non-inherited women. When adjusting for age and level of formal education, widows who were inherited by non-relatives for sexual ritual were significantly more likely to be infected than widows who were not inherited (OR = 2.07; 95%CI 1.49-2.86); widows who were inherited by relatives for sexual ritual also had elevated odds of HIV infection (OR = 1.34; 95%CI = 1.07-1.70). Widows who were inherited by relatives for companionship were less likely than women who were not inherited to be infected with HIV (OR = 0.85; 95%CI 0.63-1.14). CONCLUSIONS: HIV prevalence among inherited widows varied depending upon why and by whom they were inherited. The cohort study will determine the risk for HIV acquisition among the HIV seronegative widows in this sample.

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.

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.

Circumcision and reduced risk of self-reported penile coital injuries: results from a randomized controlled trial in Kisumu, Kenya.

PURPOSE: Injuries to the penis during intercourse represent a hypothesized mechanism by which uncircumcised men are at increased risk for HIV. There are no published, systematically collected data regarding mild penile coital trauma to our knowledge. We identified risks of self-reported penile coital injuries in men 18 to 24 years old in a randomized trial of circumcision to prevent HIV in Kisumu, Kenya. MATERIALS AND METHODS: Each participant underwent standardized interview, medical history and physical examination at baseline, and 6, 12, 18 and 24 months after enrollment. Self-reported penile coital injuries were assessed at each visit, and were defined as penis feels sore during sex, penis gets scratches, cuts or abrasions during sex, and skin of the penis bleeds after sex. Generalized estimating equation analysis estimated odds ratios for penile coital injuries. RESULTS: From February 2002 to September 2005, 2,784 participants were randomized. At baseline 1,775 (64.4%) men reported any coital injury including 1,313 (47.6%) soreness, 1,328 (48.2%) scratches, abrasions or cuts and 461 (16.7%) bleeding. On multivariable analysis coital injury risk was lower for circumcised than for uncircumcised men with soreness (OR 0.71, 95% CI 0.64-0.80), scratches/abrasions/cuts (OR 0.52, 95% CI 0.46-0.59), bleeding (OR 0.62, 95% CI 0.51-0.75) and any coital injury (OR 0.61, 95% CI 0.54-0.68). Other significant risks included increasing age, multiple recent sex partners, HSV-2 seropositivity and genital ulcers (p <0.05). Condom use, cleaning the penis soon after intercourse and being married/cohabiting were protective (p <0.05, each). CONCLUSIONS: Self-reported penile coital injuries were common in these healthy young men. Circumcised men were at lower risk for coital injuries. Verifying penile coital injuries, the mechanism of acquisition and the association with HIV risk is needed.

Spatial distribution and cluster analysis of sexual risk behaviors reported by young men in Kisumu, Kenya.

BACKGROUND: The well-established connection between HIV risk behavior and place of residence points to the importance of geographic clustering in the potential transmission of HIV and other sexually transmitted infections (STI). METHODS: To investigate the geospatial distribution of prevalent sexually transmitted infections and sexual behaviors in a sample of 18-24 year-old sexually active men in urban and rural areas of Kisumu, Kenya, we mapped the residences of 649 men and conducted spatial cluster analysis. Spatial distribution of the study participants was assessed in terms of the demographic, behavioral, and sexual dysfunction variables, as well as laboratory diagnosed STIs. To test for the presence and location of clusters we used Kulldorff's spatial scan statistic as implemented in the Satscan program. RESULTS: The results of this study suggest that sexual risk behaviors and STIs are evenly distributed in our sample throughout the Kisumu district. No behavioral or STI clusters were detected, except for condom use. Neither urban nor rural residence significantly impacted risk behavior or STI prevalence. CONCLUSION: We found no association between place of residence and sexual risk behaviors in our sample. While our results can not be generalized to other populations, the study shows that geospatial analysis can be an important tool for investigating study sample characteristics; for evaluating HIV/STI risk factors; and for development and implementation of targeted HIV and STI control programs in specifically defined populations and in areas where the underlying population dynamic is poorly understood.

Abundant expression of HIV target cells and C-type lectin receptors in the foreskin tissue of young Kenyan men.

A biological explanation for the reduction in HIV-1 (HIV) acquisition after male circumcision may be that removal of the foreskin reduces the number of target cells for HIV. The expression of potential HIV target cells and C-type lectin receptors in foreskin tissue of men at risk of HIV infection were thus analyzed. Thirty-three foreskin tissue samples, stratified by Herpes simplex virus type 2 status, were obtained from a randomized, controlled trial conducted in Kenya. The samples were analyzed by confocal in situ imaging microscopy and mRNA quantification by quantitative RT-qPCR. The presence and location of T cells (CD3(+)CD4(+)), Langerhans cells (CD1a(+)Langerin/CD207(+)), macrophages (CD68(+) or CD14(+)), and submucosal dendritic cells (CD123(+)BDCA-2(+) or CD11c(+)DC-SIGN(+)) were defined. C-type lectin receptor expressing cells were detected in both the epithelium and submucosa, and distinct lymphoid aggregates densely populated with CD3(+)CD4(+) T cells were identified in the submucosa. Although the presence of lymphoid aggregates and mRNA expression of selected markers varied between study subjects, Herpes simplex virus type 2 serostatus was not the major determinant for the detected differences. The detection of abundant and superficially present potential HIV target cells and submucosal lymphoid aggregates in foreskin mucosa from a highly relevant HIV risk group demonstrate a possible anatomical explanation that may contribute to the protective effect of male circumcision on HIV transmission.

Increased risk of HIV acquisition among Kenyan men with human papillomavirus infection.

BACKGROUND: Few data on the effect of human papillomavirus (HPV) infection on human immunodeficiency virus (HIV) acquisition are available. METHODS: HIV-seronegative, sexually active, 18-24-year-old Kenyan men participating in a randomized trial of male circumcision provided exfoliated penile cells from 2 anatomical sites (glans/coronal sulcus and shaft) at baseline. The GP5+/6+ polymerase chain reaction assay ascertained a wide range of HPV DNA types at the baseline visit. The risk of HIV infection was estimated using Kaplan-Meier methods and hazard ratios from proportional hazards models. RESULTS: Of 2168 uncircumcised men with baseline HPV data, 1089 (50%) were positive for HPV DNA. The cumulative incidence of HIV infection by 42 months was 5.8% (95% confidence interval [CI], 3.6%-7.9%) among men with HPV-positive glans/coronal sulcus specimens, versus 3.7% [95% CI, 1.8%-5.6%] among men with HPV-negative glans/coronal sulcus specimens (P = .01). Controlling for subsequent circumcision status, baseline herpes simplex virus type 2 serostatus, and sexual and sociodemographic risk factors, the hazard ratio for HIV infection among men with HPV-positive glans/coronal sulcus specimens was 1.8 (95% CI, 1.1-2.9), compared with men with HPV-negative glans/coronal sulcus specimens. CONCLUSION: The results suggest an independent increased risk of HIV seroconversion among HPV-positive men. If this finding is confirmed in other studies, HPV prevention could be another tool for HIV prevention.

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

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

Determinants of consistent condom use vary by partner type among young men in Kisumu, Kenya: a multi-level data analysis.

To evaluate whether determinants of consistent condom use vary by partner type among young sexually active Kenyan men, we conducted a cross-sectional assessment of lifetime sexual histories from a sub-sample of men enrolled in a clinical trial of male circumcision. 7913 partnerships of 1370 men were analyzed. 262 men (19%) reported never, 1018 (74%) sometimes and 92 (7%) always using a condom with their partners. Condoms were always used in 2672 (34%) of the total relationships-212 (70%) of the relationships with sex workers, 1643 (40%) of the casual and 817 (23%) of the regular/marital relationships. Factors influencing condom use varied significantly by partner type, suggesting that HIV prevention messages promoting condom use with higher-risk partners have achieved a moderate level of acceptance. However, in populations of young, single men in generalized epidemic settings, interventions should promote consistent condom use in all sexual encounters, independently of partner type and characteristics.