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To determine the effects of plasma, genital, and breast milk human immunodeficiency virus type 1 (HIV-1) and breast infections on perinatal HIV-1 transmission, a nested case-control study was conducted within a randomized clinical trial of breast-feeding and formula feeding among HIV-1-seropositive mothers in Nairobi, Kenya. In analyses comparing 92 infected infants with 187 infants who were uninfected at 2 years, maternal viral RNA levels >43,000 copies/mL (cohort median) were associated with a 4-fold increase in risk of transmission (95% confidence interval [CI], 2.2-7.2). Maternal cervical HIV-1 DNA (odds ratio [OR], 2.4; 95% CI, 1.3-4.4), vaginal HIV-1 DNA (OR, 2.3; 95% CI, 1.1-4.7), and cervical or vaginal ulcers (OR, 2.7; 95% CI, 1.2-5.8) were significantly associated with infant infection, independent of plasma virus load. Breast-feeding (OR, 1.7; 95% CI, 1.0-2.9) and mastitis (relative risk [RR], 3.9; 95% CI, 1.2-12.7) were associated with increased transmission overall, and mastitis (RR, 21.8; 95% CI, 2.3-211.0) and breast abscess (RR, 51.6; 95% CI, 4.7-571.0) were associated with late transmission (occurring >2 months postpartum). Use of methods that decrease infant exposure to HIV-1 in maternal genital secretions or breast milk may enhance currently recommended perinatal HIV-1 interventions. [ABSTRACT FROM AUTHOR]

From a cohort of female sex workers in Nairobi, Kenya, 163 women were observed to seroconvert to human immunodeficiency virus type 1 (HIV-1) and followed to study progression to HIV-1-related disease. The effect of several covariables on disease progression was studied using a Weibull proportional hazards model. The Weibull survival model was fitted to the observed incubation times. Estimates of the median duration to CDC stage IV-A and IV-C disease were 3.5 and 4.4 years, respectively. Condom use before seroconversion was associated with a reduced risk of CDC stage IV-A disease (relative risk = .64, P < .05). The incubation time of HIV-1-related disease is extremely short in this population. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence and correlates of human immunodeficiency virus (HIV)-infected cells in urethral secretions, samples were collected from 106 HIV-seropositive men with and without urethritis. HIV DNA was detected by polymerase chain reaction in 27% of 184 urethral specimens and was associated with CD4 cell depletion (P for trend, .03) and with urethritis (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.2-4.6) or gonorrhea (OR, 2.9; 95% CI, 1.5-5.8). Two multivariate models were constructed that included age, CD4 cell count < 200/mm3, and either urethritis or gonococcal infection. Detection of HIV-infected cells in urethral secretions was independently associated with < 200 CD4 cells/mm3 (OR, 2.2; 95% CI, 0.9-5.2; P = .05) and urethritis (OR, 2.7; 95% CI, 1.3-5.3; P = .003) in the first model and with gonococcal infection (OR, 3.2; 95% CI, 1.6-6.4; P < .001) in the second model. Successful treatment of gonococcal urethritis was associated with a 2-fold reduction in urethral HIV DNA (44% vs. 21%; P = .02). Thus, treatment of gonococcal urethritis may be an effective strategy for reducing HIV transmission. [ABSTRACT FROM AUTHOR]

With the objective of determining if specific sexually transmitted diseases (STDs) are associated with prematurity (birth weight less than or equal to 2500 g and gestational age less than or equal to 36 weeks), a case-control study was conducted to evaluate women for serologic evidence of syphilis and human immunodeficiency virus infection and microbiologic evidence of cervical infection with Neisseria gonorrhoeae, Chlamydia trachomatis, and Haemophilus species and vaginal infection with genital mycoplasma, Streptococcus agalactiae, and Enterobacteriaceae. Gram stains of vaginal secretions were evaluated for bacterial vaginosis. Among 166 cases and 175 controls, infection with N. gonorrhoeae was associated with preterm birth. Four percent of controls and 11% of cases were infected with N. gonorrhoeae (odds ratio 2.9, 95% confidence interval 1.2-7.2). This association was independent of age, rupture of membranes, and hypertension. Other STDs were not associated with preterm birth. The attributable risk of gonococcal infection was 14%. Gonococcal infection appears to be responsible for a substantial proportion of premature births and is theoretically preventable by antenatal case detection and treatment. [ABSTRACT FROM AUTHOR]

To examine associations between method of contraception, sexually transmitted diseases (STDs), and incident human immunodeficiency virus type 1 (HIV-1) infection, a prospective observational cohort study was done among female sex workers attending a municipal STD clinic in Mombasa, Kenya. Demographic and behavioral factors significantly associated with HIV-1 infection included type of workplace, condom use, and parity. In multivariate models, vulvitis, genital ulcer disease, vaginal discharge, and Candida vaginitis were significantly associated with HIV-1 seroconversion. Women who used depo medroxyprogesterone acetate (DMPA) had an increased incidence of HIV-1 infection (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.4-3.4). In a multivariate model controlling for demographic and exposure variables and biologic covariates, the adjusted HR for HIV-1 infection among DMPA users was 2.0 (CI, 1.3-3.1). There was a trend for an association between use of high-dose oral contraceptive pills and HIV-1 acquisition (HR, 2.6; CI, 0.8-8.5). [ABSTRACT FROM AUTHOR]

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.

Human papillomavirus (HPV)-associated penile lesions in men may increase the risk of HPV transmission to their female partners. Risk factor data on HPV-associated penile lesions are needed from regions with a high burden of cervical cancer. Visual inspection of the penis was conducted using a colposcope at the 24-month visit among participants in a randomized controlled trial of male circumcision in Kenya, from May 2006 to October 2007. All photos were read independently by two observers for quality control. Penile exfoliated cells sampled from the glans/coronal sulcus and the shaft were tested for HPV DNA using GP5+/6+ PCR and for HPV16, 18 and 31 viral loads using a real time PCR assay. Of 275 men, 151 were circumcised and 124 uncircumcised. The median age was 22 years. Circumcised men had a lower prevalence of flat penile lesions (0.7%) versus uncircumcised (26.0%); adjusted odds ratio (OR) = 0.02; 95% confidence interval (CI) = 0.003-0.1. Compared to men who were HPV negative, men who were HPV DNA positive (OR = 6.5; 95% CI = 2.4-17.5) or who had high HPV16/18/31 viral load (OR = 5.2; 95% CI = 1.1-24.4) had higher odds of flat penile lesions. Among men with flat penile lesions, HPV56 (29.0%) and 16 (25.8%) were the most common types within single or multiple infections. Flat penile lesions are much more frequent in uncircumcised men and associated with higher prevalence of HPV and higher viral loads. This study suggests that circumcision reduces the prevalence of HPV-associated flat lesions and may ultimately reduce male-to-female HPV transmission., (Copyright © 2011 UICC.)

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.

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.

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.

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.

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.

Background: Male circumcision has been shown to reduce the transmission of HIV from women to men through vaginal sex by approximately 60%. There is concern that men may engage in risk compensation after becoming circumcised, diminishing the benefits of male circumcision., Methods and Findings: We conducted qualitative interviews with 30 sexually active circumcised men in Kisumu, Kenya from March to November 2008. Most respondents reported no behavior change or increasing protective sexual behaviors including increasing condom use and reducing the number of sexual partners. A minority of men reported engaging in higher risk behaviors either not using condoms or increasing the number of sex partners. Circumcised respondents described being able to perform more rounds of sex, easier condom use, and fewer cuts on the penis during sex., Conclusions: Results illustrate that information about MC's protection against HIV has disseminated into the larger community and MC accompanied by counseling and HIV testing can foster positive behavior change and maintain sexual behavior.

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.

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., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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.

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.

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.

Human papillomavirus (HPV) prevalence was estimated from 2,705 sexually active, uncircumcised, human immunodeficiency virus seronegative men aged 17-28 years in Kisumu, Kenya. HPV prevalence was 51.1% (95% confidence interval: 49.2-53.0%) in penile cells from the glans/coronal sulcus and/or shaft. HPV prevalence varied by anatomical site, with 46.5% positivity in the glans/coronal sulcus compared with 19.1% in the shaft (p < 0.0001). High-risk HPV was detected in 31.2% of glans and 12.3% of shaft samples (p < 0.0001). HPV16 was the most common type and 29.2% of men were infected with more than one HPV type. Risk factors for HPV infection included presence of C. trachomatis, N. gonorrhea, self-reported sexually transmitted infections, and less frequent bathing. Lifetime number of sexual partners and herpes simplex virus type-2 seropositivity were also marginally associated with HPV infection.

Objectives: Several studies have demonstrated an association between herpes simplex virus type 2 (HSV-2) and HIV-1, but available data on risk factors for HSV-2 acquisition are limited. The objective of this analysis was to determine the incidence and risk factors for HSV-2 acquisition among HIV-1-seronegative female sex workers in Kenya., Methods: Between February 1993 and December 2006, HIV-1-seronegative women attending a municipal sexually transmitted infection (STI) clinic were invited to enroll in a prospective cohort study. Screening for HIV-1 and STIs were done at monthly follow-up visits. Archived blood samples were tested for HSV-2., Results: Of 1527 HIV-1-seronegative women enrolled, 302 (20%) were HSV-2 seronegative at baseline of whom 297 had at least one follow-up visit. HSV-2 incidence was high (23 cases/100 person-years; 115 cases). In multivariate analysis, HSV-2 was significantly associated with more recent entry into sex work, workplace and higher number of sex partners per week. Condom use was protective, although this was statistically significant only for the intermediate strata (25-75% condom use; HR 0.43; p = 0.05). There were statistical trends for bacterial vaginosis to increase HSV-2 risk (HR 1.56; p = 0.07) and for oral contraceptive use to decrease risk (HR 0.50; p = 0.08). The 23% annual HSV-2 incidence in this study is among the highest reported anywhere in the world., Conclusions: Women were at increased risk if they had recently entered sex work, had a higher number of sex partners or worked in bars. HSV-2 risk reduction interventions are urgently needed among high-risk African women.

Objective: Vaginal colonisation with Lactobacillus species is characteristic of normal vaginal ecology. The absence of vaginal lactobacilli, particularly hydrogen peroxide (H(2)O(2))-producing isolates, has been associated with symptomatic bacterial vaginosis (BV) and increased risk for HIV-1 acquisition. Identification of factors associated with vaginal Lactobacillus colonisation may suggest interventions to improve vaginal health., Methods: We conducted a prospective cohort study of correlates of vaginal Lactobacillus colonisation among Kenyan HIV-1 seronegative female sex workers. At monthly follow-up visits, vaginal Lactobacillus cultures were obtained. Generalised estimating equations were used to examine demographic, behavioural and medical correlates of Lactobacillus isolation, including isolation of H(2)O(2)-producing strains., Results: Lactobacillus cultures were obtained from 1020 women who completed a total of 8896 follow-up visits. Vaginal washing, typically with water alone or with soap and water, was associated with an approximately 40% decreased likelihood of Lactobacillus isolation, including isolation of H(2)O(2)-producing strains. Recent antibiotic use, excluding metronidazole and treatments for vaginal candidiasis, reduced Lactobacillus isolation by approximately 30%. H(2)O(2)-producing lactobacilli were significantly less common among women with Trichomonas vaginalis infection and those who were seropositive for herpes simplex virus type 2. In contrast, H(2)O(2)-producing lactobacilli were significantly more common among women with concurrent vaginal candidiasis., Conclusions: Modifiable biological and behavioural factors are associated with Lactobacillus colonisation in African women. Our results suggest intervention strategies to improve vaginal health in women at high risk for HIV-1.

Background: We examined the effect of male circumcision on the acquisition of 3 nonulcerative sexually transmitted infections (STIs)., Methods: We evaluated the incidence of STI among men aged 18-24 years enrolled in a randomized trial of circumcision to prevent human immunodeficiency virus (HIV) infection in Kisumu, Kenya. The outcome was first incident nonulcerative STI during 2 years of follow-up. STIs examined were laboratory-detected Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis infection., Results: There were 342 incident infections among 2655 men followed up. The incidences of infection due to N. gonorrhoeae, C. trachomatis, and T. vaginalis were 3.48, 4.55, and 1.32 cases per 100 person-years, respectively. The combined incidence of N. gonorrhoeae and C. trachomatis infection was 7.26 cases per 100 person-years (95% confidence interval, 6.49-8.13 cases per 100 person-years). The incidences of these STIs, individually or combined, did not differ by circumcision status as a time-dependent variable or a fixed variable based on assignment. Risks for incident STIs in multivariate analysis included an STI at enrollment, multiple sex partners within <30 days, and sexual intercourse during menses in the previous 6 months; condom use was protective., Conclusions: Circumcision of men in this population did not reduce their risk of acquiring these nonulcerative STIs. Improved STI control will require more-effective STI management, including partner treatment and behavioral risk reduction counseling.

Background: It has been suggested that vaginal colonization with lactobacilli may reduce the risk of vulvovaginal candidiasis (VVC), but supporting data are limited. Our objective was to determine the relationship between vaginal bacterial flora and VVC., Methods: We conducted a prospective cohort analysis that involved 151 Kenyan sex workers. At monthly follow-up visits, VVC was defined as the presence of yeast buds, pseudohyphae, or both on a wet preparation (including potassium hydroxide preparation) of vaginal secretions. Generalized estimating equations were used to identify correlates of VVC., Results: Participants returned for a median of 12 visits (interquartile range, 11-12 visits). VVC was identified at 162 visits, including 26 involving symptomatic VVC. Bacterial vaginosis was associated with fewer episodes of VVC (adjusted odds ratio [aOR], 0.29 [95% confidence interval {CI}, 0.16-0.50]). After excluding women with concurrent bacterial vaginosis, another possible cause of vaginal symptoms, the likelihood of symptomatic VVC was higher among those who had had yeast identified on wet preparation of vaginal secretions during the past 60 days (aOR, 4.06 [95% CI, 1.12-14.74]) and those with concurrent vaginal Lactobacillus colonization (aOR, 3.75 [95% CI, 1.30-10.83])., Conclusions: Contrary to the commonly posited hypothesis that vaginal Lactobacillus colonization has a protective effect, we found that such colonization was associated with a nearly 4-fold increase in the likelihood of symptomatic VVC.

Background: In certain parts of Africa, type-specific herpes simplex virus type 2 (HSV-2) ELISAs may have limited specificity. To date, no study has been conducted to validate HerpeSelect and Kalon type-specific HSV-2 ELISAs using both the Western blot and recombinant gG ELISA inhibition testing as reference standards., Methods: A total of 120 men who were HIV seronegative (aged 18-24 years) provided blood samples. HSV-2 IgG serum antibodies were detected using four different methods: HerpeSelect HSV-2 ELISA (n = 120), Kalon HSV-2 ELISA (n = 120), University of Washington Western blot (n = 101) and a recombinant inhibition test (n = 93)., Results: HSV-2 seroprevalence differed significantly by HSV-2 detection method, ranging from 24.8% with the Western blot to 69.8% with the HerpeSelect ELISA. Using the Western blot as the reference standard, the HerpesSelect had the highest sensitivity for HSV-2 antibody detection (100%) yet lowest specificity (40%). Similar results were obtained using the inhibition test as the reference standard. The sensitivity and specificity of the Kalon test versus the Western blot were 92% and 79%, respectively, and 80% and 82% versus the inhibition test. Using the inhibition test as the reference standard, the sensitivity of the Western blot appeared low (49%)., Conclusions: In men in western Kenya who were HIV seronegative, the HerpeSelect and Kalon type-specific ELISAs had high sensitivities yet limited specificities using the Western blot as reference standard. Overall, the Kalon ELISA performed better than the HerpeSelect ELISA in these young men from Kisumu. Further understanding is needed for the interpretation of HSV-2 inhibition or ELISA test positive/ Western blot seronegative results. Before HSV-2 seropositivity may be reliably reported in selected areas of Africa, performance studies of HSV-2 serological assays in individual geographical areas are recommended.

Objective: To evaluate relationships between HIV-1 evolution, including immune evasion, and markers of disease progression during chronic infection., Design: HIV-1 evolution and disease progression markers were evaluated over approximately 5 years of infection among 37 Kenyan women from a prospective, seroincident cohort. Evolution was measured in two genes, gag and env, which are primary targets of cellular and humoral immune responses, respectively., Methods: Proviral HIV-1 gag and env sequences were obtained from early and chronic infection when plasma viral load and CD4 cell counts were available. Human leukocyte antigen types were obtained to identify changes in gag cytotoxic T-lymphocyte epitopes. The breadth of the neutralizing antibody response was measured for each woman's plasma against a panel of six viruses. Tests of association were performed between virus evolution (diversity, divergence, and ratio of nonsynonymous to synonymous divergence), markers of disease progression (viral load and CD4 cell count), and immune parameters (gag cytotoxic T lymphocyte epitope mutation and neutralizing antibody breadth)., Results: HIV-1 gag and env diversity and divergence were highly correlated in early and late infection. Divergence in gag was strongly correlated with viral load, largely because of the accumulation of synonymous changes. Mutation in gag cytotoxic T-lymphocyte epitopes was associated with higher viral load. There was evidence for adaptive evolution in env, but the extent of env evolution was only weakly associated with neutralizing antibody breadth., Conclusion: Our results indicate that HIV-1 evolution in gag and env is highly correlated but exhibits gene-specific differences. The different immune pressures on these genes may partly explain differences in evolution and consequences for HIV-1 disease progression.

Introduction: Male circumcision is being promoted for HIV prevention in high-risk heterosexual populations. However, there is a concern that circumcision may impair sexual function., Aim: To assess adult male circumcision's effect on men's sexual function and pleasure., Methods: Participants in a controlled trial of circumcision to reduce HIV incidence in Kisumu, Kenya were uncircumcised, HIV negative, sexually active men, aged 18-24 years, with a hemoglobin >or=9.0 mmol/L. Exclusion criteria included foreskin covering less than half the glans, a condition that might unduly increase surgical risks, or a medical indication for circumcision. Participants were randomized 1:1 to either immediate circumcision or delayed circumcision after 2 years (control group). Detailed evaluations occurred at 1, 3, 6, 12, 18, and 24 months., Main Outcome Measures: (i) Sexual function between circumcised and uncircumcised men; and (ii) sexual satisfaction and pleasure over time following circumcision., Results: Between February 2002 and September 2005, 2,784 participants were randomized, including the 100 excluded from this analysis because they crossed over, were not circumcised within 30 days of randomization, did not complete baseline interviews, or were outside the age range. For the circumcision and control groups, respectively, rates of any reported sexual dysfunction decreased from 23.6% and 25.9% at baseline to 6.2% and 5.8% at month 24. Changes over time were not associated with circumcision status. Compared to before they were circumcised, 64.0% of circumcised men reported their penis was "much more sensitive," and 54.5% rated their ease of reaching orgasm as "much more" at month 24., Conclusions: Adult male circumcision was not associated with sexual dysfunction. Circumcised men reported increased penile sensitivity and enhanced ease of reaching orgasm. These data indicate that integration of male circumcision into programs to reduce HIV risk is unlikely to adversely effect male sexual function.

Background: Three randomized controlled trials (RCTs) have confirmed that male circumcision (MC) significantly reduces acquisition of HIV-1 infection among men. The objective of this study was to perform a comprehensive, prospective evaluation of risk compensation, comparing circumcised versus uncircumcised controls in a sample of RCT participants., Methods and Findings: Between March 2004 and September 2005, we systematically recruited men enrolled in a RCT of MC in Kenya. Detailed sexual histories were taken using a modified Timeline Followback approach at baseline, 6, and 12 months. Participants provided permission to obtain circumcision status and laboratory results from the RCT. We evaluated circumcised and uncircumcised men's sexual behavior using an 18-item risk propensity score and acquisition of incident infections of gonorrhea, chlamydia, and trichomoniasis. Of 1780 eligible RCT participants, 1319 enrolled (response rate = 74%). At the baseline RCT visit, men who enrolled in the sub-study reported the same sexual behaviors as men who did not. We found a significant reduction in sexual risk behavior among both circumcised and uncircumcised men from baseline to 6 (p<0.01) and 12 (p = 0.05) months post-enrollment. Longitudinal analyses indicated no statistically significant differences between sexual risk propensity scores or in incident infections of gonorrhea, chlamydia, and trichomoniasis between circumcised and uncircumcised men. These results are based on the most comprehensive analysis of risk compensation yet done., Conclusion: In the context of a RCT, circumcision did not result in increased HIV risk behavior. Continued monitoring and evaluation of risk compensation associated with circumcision is needed as evidence supporting its' efficacy is disseminated and MC is widely promoted for HIV prevention.

Background: Vaginal infections are common and have been associated with increased risk for acquisition of human immunodeficiency virus type 1 (HIV-1)., Methods: We conducted a randomized trial of directly observed oral treatment administered monthly to reduce vaginal infections among Kenyan women at risk for HIV-1 acquisition. A trial intervention of 2 g of metronidazole plus 150 mg of fluconazole was compared with metronidazole placebo plus fluconazole placebo. The primary end points were bacterial vaginosis (BV), vaginal candidiasis, trichomoniasis vaginalis (hereafter, "trichomoniasis"), and colonization with Lactobacillus organisms., Results: Of 310 HIV-1-seronegative female sex workers enrolled (155 per arm), 303 were included in the primary end points analysis. A median of 12 follow-up visits per subject were recorded in both study arms (P = .8). Compared with control subjects, women receiving the intervention had fewer episodes of BV (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.49-0.63) and more frequent vaginal colonization with any Lactobacillus species (HR, 1.47; 95% CI, 1.19-1.80) and H(2)O(2)-producing Lactobacillus species (HR, 1.63; 95% CI, 1.16-2.27). The incidences of vaginal candidiasis (HR, 0.84; 95% CI, 0.67-1.04) and trichomoniasis (HR, 0.55; 95% CI, 0.27-1.12) among treated women were less than those among control subjects, but the differences were not statistically significant., Conclusions: Periodic presumptive treatment reduced the incidence of BV and promoted colonization with normal vaginal flora. Vaginal health interventions have the potential to provide simple, female-controlled approaches for reducing the risk of HIV-1 acquisition.

Objectives: To identify factors associated with herpes simplex virus type 2 (HSV-2) infection among men aged 18-24 in Kisumu, Kenya., Methods: Baseline data from a randomised trial of male circumcision were analysed. Participants were interviewed for sociodemographic and behavioural risks. The outcome was HSV-2 by antibody status. Risk factors were considered singly and in combination through logistic regression models., Results: Among 2771 uncircumcised men, 766 (27.6%; 95% confidence interval (CI) 26.0% to 29.3%) tested antibody positive for HSV-2. The median age at first sex was 16 years, and the median number of lifetime sexual partners was four. HSV-2 seroprevalence increased from 19% among 18-year-olds to 43% among 24-year-olds (p<0.001). In multivariable analysis, statistically significant risks for infection were increasing age (adjusted odds ratio (AOR) = 1.22-2.58), being married or having a live-in female partner (AOR = 1.80; 95% CI 1.28 to 2.53), preferring "dry" sex (AOR = 1.39; 95% CI 1.14 to 1.69), reported penile cuts or abrasions during sex (AOR = 1.58; 95% CI 1.32 to 1.91), increasing lifetime sex partners (multiple response categories; AORs ranging from 1.65 to 1.97), and non-student occupation (multiple response categories; AORs ranging from 1.44 to 1.93). Risk decreased with reported condom used at last sex (AOR = 0.82; 95% CI 0.68 to 0.99)., Conclusion: Primary prevention efforts should be initiated at an early age. The same behavioural interventions used currently for HIV prevention-abstinence, reducing the number of sex partners and increasing condom use-should be effective for HSV-2 prevention.

We investigated the association between albumin levels and HIV-1 disease progression among 78 Kenyan women followed from before infection through a median of 70 months. With HIV-1 acquisition, median albumin decreased from 38.5 g/liter to 36.8 g/liter (p = 0.07) and the prevalence of hypoalbuminemia increased from 16% to 32% (p = 0.02). Each 1 g/liter decrease in albumin with HIV-1 acquisition was associated with a 13% increase (p = 0.01) in the risk of progressing to a CD4 count <200 cells/mul, after adjustment for set point plasma viral load. A decrease in albumin of over 10% was associated with a 3.5-fold increase in the risk of progressing to a CD4 count <200 cells/mul (95% CI 1.4-9.0, p = 0.008). Trends for an increased risk of mortality were also seen. A greater decrease in albumin levels accompanying HIV-1 acquisition may be a marker for changes in early infection associated with more rapid disease progression.

Background: Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results. A recent study from Uganda and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 (HSV-2), but not if they were HSV-2 seropositive., Objective: To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population. Hormonal contraception has previously been associated with increased HIV-1 risk in this population., Methods: Data were from a prospective cohort study of 1206 HIV-1 seronegative sex workers from Mombasa, Kenya who were followed monthly. Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases., Results: : Two hundred and thirty-three women acquired HIV-1 (8.7/100 person-years). HSV-2 prevalence (81%) and incidence (25.4/100 person-years) were high. In multivariate analysis, including adjustment for HSV-2, HIV-1 acquisition was associated with use of oral contraceptive pills [adjusted hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.00-2.13] and depot medroxyprogesterone acetate (adjusted HR, 1.73; 95% CI, 1.28-2.34). The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women. HSV-2 infection was associated with elevated HIV-1 risk (adjusted HR, 3.58; 95% CI, 1.64-7.82)., Conclusions: In this group of high-risk African women, hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition. HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus.

Background: Low vitamin E levels are often found in HIV-1 infection, and studies have suggested that higher levels may decrease the risk of disease progression. However, vitamin E supplementation has also been reported to increase CCR5 expression, which could increase HIV-1 replication. We hypothesized that vitamin E levels at HIV-1 acquisition may influence disease progression., Methods: Vitamin E status was measured in stored samples from the last pre-infection visit for 67 Kenyan women with reliably estimated dates of HIV-1 acquisition. Regression analyses were used to estimate associations between pre-infection vitamin E and plasma viral load, time to CD4 count <200 cells/muL, and mortality., Results: After controlling for potential confounding factors, each 1 mg/L increase in pre-infection vitamin E was associated with 0.08 log10 copies/mL (95% CI -0.01 to +0.17) higher set point viral load and 1.58-fold higher risk of mortality (95% CI 1.15-2.16). The association between higher pre-infection vitamin E and mortality persisted after adjustment for set point viral load (HR 1.55, 95% CI 1.13-2.13)., Conclusion: Higher pre-infection vitamin E levels were associated with increased mortality. Further research is needed to elucidate the role vitamin E plays in HIV-1 pathogenesis.

Background: Bacterial vaginosis (BV) is highly prevalent among African women and has been associated with adverse pregnancy outcomes, sexually transmitted diseases, and HIV-1., Goal: The goal of this study was to analyze the relationship among intravaginal practices, bathing, and BV., Study Design: The authors conducted a cross-sectional study of HIV-1-seronegative Kenyan female sex workers without symptoms of vaginal infections., Results: Of 237 women enrolled, 206 (87%) reported vaginal washing using either a finger or cloth. Increasing frequency of vaginal washing was associated with a higher likelihood of BV (chi(2) test for trend, P = 0.05). In multivariate analysis, vaginal lubrication with petroleum jelly (odds ratio [OR] = 2.8, 95% confidence interval [CI] = 1.4-5.6), lubrication with saliva (OR = 2.3, 95% CI = 1.1-4.8), and bathing less than the median for the cohort (14 times/week; OR = 4.6, 95% CI = 1.2-17.5) were associated with a significantly higher likelihood of BV., Conclusions: Modification of intravaginal and general hygiene practices should be evaluated as potential strategies for reducing the risk of BV.

Background: Antiretroviral therapy (ART) may decrease HIV-1 infectivity in women by reducing genital HIV-1 shedding., Objectives: To evaluate the time course and magnitude of decay in cervical and vaginal HIV-1 shedding as women initiate ART., Methods: This prospective, observational study of 20 antiretroviral-naive women initiating ART with stavudine, lamivudine, and nevirapine measured HIV-1 RNA in plasma, cervical secretions, and vaginal secretions. Qualitative polymerase chain reaction estimated HIV-1 DNA in cervical and vaginal samples. Perelson's two-phase viral decay model and non-linear random effects were used to compare RNA decay rates. Decreases in proviral DNA were evaluated using logistic regression and generalized estimating equations., Results: Significant decreases in the quantity of HIV-1 RNA were observed by day 2 in plasma (P < 0.001), day 2 in cervical secretions (P = 0.001), and day 4 in vaginal secretions (P < 0.001). Modeled initial and subsequent RNA decay rates in plasma, cervical secretions, and vaginal secretions were 0.6, 0.8, and 1.2 log10 virions/day, and 0.04, 0.05, and 0.06 log10 virions/day, respectively. The initial decay rate for vaginal HIV-1 RNA was more rapid than for plasma RNA (P = 0.02). Detection of HIV-1 DNA decreased significantly in vaginal secretions during the first week (P < 0.001). At day 28, 10 women had detectable HIV-1 RNA or proviral DNA in genital secretions., Conclusions: Genital HIV-1 shedding decreased rapidly after ART initiation, consistent with a rapid decrease in infectivity. However, incomplete viral suppression in half of these women may indicate an ongoing risk of transmission.

Introduction: We examined male circumcision outcomes among young adults in an African setting., Materials and Methods: Participants were healthy, sexually active, uncircumcised, HIV-seronegative males aged 18-24 years. The main outcomes measured included complications, healing, satisfaction and resumption of activities., Results: Of 1,475 procedures, 26 (1.8%) were associated with 27 adverse events, most commonly wound disruption/delayed healing (0.6%), wound infection (0.4%), and bleeding (0.3%). Adverse events per clinician averaged 3.8 and 2.1% for procedures 1-100 and 101-200, respectively, and <1% for procedures 201-300, 301-400 and >400, respectively (p < 0.001). Participants resumed normal general activities after a median of 1 postoperative day and 93% with regular employment resumed working within 1 week. After 30 days, 99% of participants reported being very satisfied. After 90 days, 65% reported having had sex, 45% reported that their partners had expressed an opinion, 92% of whom were very satisfied with the outcome., Conclusions: Safe and acceptable adult male circumcision services can be delivered in developing country settings., (Copyright 2007 S. Karger AG, Basel.)

Few data are available on genital tract viral replication early after HIV-1 acquisition, when infectivity is high. We compared cervical HIV-1 RNA from 60 women with paired samples from within 90 days after HIV-1 acquisition and at viral setpoint (4-24 months). Cervical HIV-1 was higher in early compared with setpoint samples (mean 3.43 versus 2.85 log10 copies/swab, P < 0.001). After adjusting for HIV-1-plasma RNA, cervical HIV-1 RNA from 30 days or less after infection was increased by 0.45 log10 copies/swab (P = 0.006).

Background: Low serum selenium has been associated with lower CD4 counts and greater mortality among HIV-1-seropositive individuals, but most studies have not controlled for serum albumin and the presence of an acute phase response., Methods: A cross-sectional study was conducted to evaluate relationships between serum selenium concentrations and CD4 count, plasma viral load, serum albumin, and acute phase response markers among 400 HIV-1-seropositive women., Results: In univariate analyses, lower CD4 count, higher plasma viral load, lower albumin, and the presence of an acute phase response were each significantly associated with lower serum selenium concentrations. In multivariate analyses including all four of these covariates, only albumin remained significantly associated with serum selenium. For each 0.1 g/dl increase in serum albumin, serum selenium increased by 0.8 microg/l (p < 0.001). Women with an acute phase response also had lower serum selenium (by 5.6 microg/l, p = 0.06)., Conclusion: Serum selenium was independently associated with serum albumin, but not with CD4 count or plasma viral load, in HIV-1-seropositive women. Our findings suggest that associations between lower serum selenium, lower CD4 count, and higher plasma viral load may be related to the frequent occurrence of low serum albumin and the acute phase response among individuals with more advanced HIV-1 infection.

Background: There is limited information on the natural history of human immunodeficiency virus type 1 (HIV-1) infection in Africa, especially from individuals with well-defined dates of infection. We used data from a prospective cohort study of female sex workers in Mombasa, Kenya, who were followed up monthly from before the date of HIV-1 infection., Methods: Antiretroviral-naive women who had a well-defined date of HIV-1 infection were included in this analysis. The effects of set point plasma viral load (measured 4-24 months after infection), early CD4+ cell count, and symptoms of acute HIV-1 infection on mortality were assessed using Cox proportional hazards analysis., Results: Among 218 women, the median duration of follow-up after HIV-1 infection was 4.6 years. Forty women died, and at 8.7 years (the time of the last death), the cumulative survival rate was 51% by Kaplan-Meier analysis. Higher set point viral load, lower early CD4+ cell count, and more-symptomatic acute HIV-1 illness each predicted death. In multivariate analysis, set point viral load (hazard ratio [HR], 2.28 per 1 log10 copies/mL increase; P=.001) and acute HIV-1 illness (HR, 1.14 per each additional symptom; P=.05) were independently associated with higher mortality., Conclusion: Among this group of African women, the survival rate was similar to that for HIV-1-infected individuals in industrialized nations before the introduction of combination antiretroviral therapy. Higher set point viral load and more-severe acute HIV-1 illness predicted faster progression to death. Early identification of individuals at risk for rapid disease progression may allow closer clinical monitoring, including timely initiation of antiretroviral treatment.

Background: Guidelines for initiating antiretrovirals are based on markers of advanced disease and are not directly linked to markers of HIV-1 transmission such as viral shedding., Methods: We evaluated genital HIV-1 shedding and risk behavior among 650 antiretroviral-naïve women stratified by WHO criteria for initiating antiretrovirals based on CD4 count and symptoms., Results: Genital HIV-1 concentrations increased in stepwise fashion with declining CD4 counts and the presence of symptoms. Compared with the reference group (asymptomatic with CD4 >350 cells/microL), those with advanced immunosuppression (CD4 <200 cells/microL) had significantly higher cervical HIV-1 RNA concentrations (2.4 log10 copies/swab vs. 3.8 log10 copies/swab, P < 0.001). However, women with CD4 counts <200 cells/microL were also less likely than the reference group to report intercourse during the past week (58% vs. 26%, P < 0.001)., Conclusions: Antiretroviral guidelines focusing on individuals with the most advanced immunosuppression will target those with the highest genital HIV-1 concentrations. However, individuals with less advanced immunosuppression also have high levels of genital HIV-1 and may be more sexually active. The effect of increased antiretroviral availability on the spread of HIV-1 might be enhanced by extending treatment, in addition to other risk reduction services, to those with less advanced disease.

Numerous epidemiologic studies have found significant associations between lack of circumcision and HIV-1 acquisition in men. To our knowledge, this is the first study of human foreskin tissue that examines biologic mechanisms that increase susceptibility of uncircumcised African men to HIV-1. Foreskin specimens from 20 men with and 19 men with no history of sexually transmitted infections were examined for HIV-1 target cells. Most Langerhans cells were found in the epithelium; most CD4+ T cells and macrophages were in the submucosa. There were no differences in HIV-1 target cells between men with and those without history of sexually transmitted infections. However Langerhans cells and macrophages were more abundant in the group with a history of infection. The densities and positions of HIV-1 target cells in the foreskin tissue of these Kenyan men indicate that the inner mucosal surface of the human foreskin contains cells that make it highly susceptible to HIV infection.

Background: No prospective study has examined the risk of HIV-1 acquisition associated with vaginal washing, although intravaginal practices have been identified as potentially important contributors to HIV-1 susceptibility., Objective: To evaluate the contribution of vaginal washing to incident HIV-1 infection., Design: Prospective cohort study., Methods: Data were derived from a 10-year study of risk factors for HIV-1 acquisition among 1270 Kenyan female sex workers. Intravaginal practices were ascertained at study enrollment. At monthly follow-up visits, women completed a standardized interview and specimens were collected for diagnosis of HIV-1 and genital tract infections., Results: : Compared with women who did not perform vaginal washing, there was an increased risk for acquiring HIV-1 among women who used water [adjusted hazard ratio (HR), 2.64; 95% confidence interval (CI), 1.00-6.97] or soap (adjusted HR 3.84; 95% CI, 1.51-9.77) to clean inside the vagina, after adjustment for demographic factors, sexual behavior, and sexually transmitted infections. Furthermore, women who performed vaginal washing with soap or other substances were at higher risk for HIV-1 compared with those who used water alone (adjusted HR, 1.47; 95% CI, 1.02-2.13)., Conclusions: In populations where vaginal washing is common, this practice may be an important factor promoting the spread of HIV-1. Intervention strategies aimed at modifying intravaginal practices should be evaluated as a possible female-controlled HIV-1 prevention strategy.

Objective: To develop a standard procedure for male circumcision in a resource-poor medical setting and prospectively evaluate the outcome in a randomized, controlled trial with the incidence of human immunodeficiency virus (HIV) as the main outcome, as studies suggest that circumcision is associated with a lower incidence of HIV and other sexually transmitted infections in high-risk populations., Subjects and Methods: Healthy, uncircumcised, HIV-seronegative men aged 18-24 years from Kisumu District, Kenya, were offered participation in a clinical trial using a standard circumcision procedure based on "usual" medical procedures in Western Kenya. The follow-up included visits at 3, 8 and 30 days after circumcision, with additional visits if necessary. Healing, satisfaction and resumption of activities were assessed at these visits and 3 months from randomization., Results: Overall, 17 (3.5%) of the 479 circumcisions were associated with adverse events judged definitely, probably or possibly related to the procedure. The most common adverse events were wound infections (1.3%), bleeding (0.8%), and delayed wound healing or suture line disruption (0.8%). After 30 days, 99% of participants reported being very satisfied with the procedure; approximately 23% reported having had sex and 15% reported that their partners had expressed an opinion, all of whom were very satisfied with the outcome. About 96% of the men resumed normal general activities within the first week after the procedure., Conclusion: Safe and acceptable adult male circumcision services can be delivered in developing countries should male circumcision ultimately be advocated as a public-health measure.