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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial.

BACKGROUND: Male circumcision could provide substantial protection against acquisition of HIV-1 infection. Our aim was to determine whether male circumcision had a protective effect against HIV infection, and to assess safety and changes in sexual behaviour related to this intervention. METHODS: We did a randomised controlled trial of 2784 men aged 18-24 years in Kisumu, Kenya. Men were randomly assigned to an intervention group (circumcision; n=1391) or a control group (delayed circumcision, 1393), and assessed by HIV testing, medical examinations, and behavioural interviews during follow-ups at 1, 3, 6, 12, 18, and 24 months. HIV seroincidence was estimated in an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, with the number NCT00059371. FINDINGS: The trial was stopped early on December 12, 2006, after a third interim analysis reviewed by the data and safety monitoring board. The median length of follow-up was 24 months. Follow-up for HIV status was incomplete for 240 (8.6%) participants. 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped. The 2-year HIV incidence was 2.1% (95% CI 1.2-3.0) in the circumcision group and 4.2% (3.0-5.4) in the control group (p=0.0065); the relative risk of HIV infection in circumcised men was 0.47 (0.28-0.78), which corresponds to a reduction in the risk of acquiring an HIV infection of 53% (22-72). Adjusting for non-adherence to treatment and excluding four men found to be seropositive at enrollment, the protective effect of circumcision was 60% (32-77). Adverse events related to the intervention (21 events in 1.5% of those circumcised) resolved quickly. No behavioural risk compensation after circumcision was observed. INTERPRETATION: Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa. Where appropriate, voluntary, safe, and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible.

Adult male circumcision: effects on sexual function and sexual satisfaction in Kisumu, Kenya.

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.

Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women.

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.

Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding.

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.

A decrease in albumin in early HIV type 1 infection predicts subsequent disease progression.

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.

Higher pre-infection vitamin E levels are associated with higher mortality in HIV-1-infected Kenyan women: a prospective study.

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.

Vaginal washing and increased risk of HIV-1 acquisition among African women: a 10-year prospective study.

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.

High levels of cervical HIV-1 RNA during early HIV-1 infection.

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).