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Introduction: Low-level HIV epidemic settings like Singapore face the challenge of reaching men at-risk who have less contact with programmes. We investigated patterns of meeting platform use by men seeking male sexual partners (MSM) as potential marker of risk to differentiate sub-groups for interventions., Methods: Latent Class Analysis (LCA) was applied to a survey sample of MSM recruited from bars/clubs, saunas and a smartphone application, using purposive sampling. The best-fit LCA model which identified homogeneous sub-groups with similar patterns of meeting platform was factored in multivariable regression to identify associations with risk behaviors on the pathway to HIV infection., Results: Overall 1,141 MSM were recruited from bars/clubs ( n = 426), saunas ( n = 531), and online ( n = 184). Five patterns emerged, reflecting salient platform use characteristics: Sauna-centric (SC; n = 413), App-centric (AC; n = 276), Multiple-platforms (MP; n = 123), Platform-inactive (PI; n = 257), and "Do not hook up" (DNH; n = 72) classes. Men in the SC and MP classes had high probabilities of using saunas to meet partners; SC were older and less likely to have disclosed their sexual orientation. The MP class had high probabilities of connecting across all platforms in addition to saunas and more likely to have disclosed their sexual orientation, than the PI class. Men in the SC and MP classes had twice the odds of reporting multiple sex partners (aOR SC = 2.1; 95%CI: 1.33.2; aOR MP = 2.2; 95%CI: 1.14.6). Single/non-partnered MSM and those using alcohol/drugs during sex had 1.7 (95%CI: 1.22.5) and 3.2 (95%CI: 2.05.1) the odds respectively, of reporting multiple sex partners. The SC and MP classes had higher odds of engaging in group sex while MSM using alcohol/drugs during sex had twice the odds of reporting group sex. Alcohol/drugs and group sex were independently associated with condomless sex (as was lower education). Group sex, alcohol/drugs during sex, disclosure of sexual orientation or being Singaporean/permanent resident were associated with recent testing for HIV., Discussion: The five distinct risk profiles identified can help tailor differentiated HIV interventions-combined with field knowledge and other prevention-to expand HIV self-testing, Pre-Exposure Prophylaxis and other services (e.g., Mpox vaccination) to sub-groups at risk., Competing Interests: CK is employed by Action for AIDS Singapore. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tavitian-Exley, Hao, Chen, Wong, Kwok and Toh.)

Hormonal contraception (HC), particularly injectable depot-medroxyprogesterone acetate (DMPA), has been associated with increased HIV acquisition and higher levels of cervical regulated upon activation, normal T-cell expressed, and secreted (RANTES), also associated with HIV seroconversion. Longitudinal changes in cervical immunity associated with DMPA and combined oral contraceptives (COCs) have not been studied. Cervical samples from 216 HIV seroconverters in Uganda and Zimbabwe with matched samples from 727 HIV-uninfected controls were collected at two quarterly visits before (t - 2, t - 1), at (t0), and two visits following (t + 1, t + 2) HIV seroconversion and corresponding visits for HIV-negative controls. We measured 10 biomarkers of inflammation and immunity and used generalized linear models to estimate and compare biomarker levels across HIV status, contraceptive, and pregnancy groups. Biomarkers remained relatively stable across visits for controls, while in HIV-infected women cervical immunity started to change before seroconversion with RANTES and BD-2 increased and secretory leukocyte protease inhibitor (SLPI) decreased at t - 1 and continued to change at t0 with ICAM-1 up and IL-8 down and with more biomarkers after seroconversion (IL-1β, IL-6, MIP-3α, VEGF, and IL-1RA down and IL-1RA:IL-1β ratio up). In multivariable analyses, seroconverters had higher BD-2 at t - 1, higher RANTES and lower SLPI from t - 1 through t + 2, and lower IL-8 and IL-1RA at and/or after seroconversion compared to nonseroconverters. Compared to non-HC users, DMPA users had higher RANTES at all visits and lower BD-2 at t - 2 through t0, while COC users and pregnant women had higher IL-8 and SLPI at all visits; COC users also had lower BD-2 preseroconversion; pregnant women had lower RANTES at t0 - t + 2. Longitudinal patterns of cervical immunity differ between HIV seroconverters and HIV-negative women; seroconverters demonstrate increased RANTES and decreased SLPI starting before and continuing postseroconversion. Furthermore, these patterns are differentially regulated by DMPA, COC, and pregnancy.

Background: Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type., Methods and Findings: We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa and was 1.7% (95% CI: 1.2%, 2.6%; I2 = 55.2%) in Southern/Eastern Africa. Across the three primary region/population groups, HSV-2 and BV prevalence was high among 25-49-year-olds (ranging from 70% to 83% and 33% to 44%, respectively). The main study limitation is that the data are not from random samples of the target populations., Conclusions: Combining data from 18 HIV prevention studies, our findings highlight important features of STI/BV epidemiology among sub-Saharan African women. This methodology can be used where routine STI surveillance is limited and offers a new approach to obtaining critical information on STI and BV prevalence in LMICs.

In the majority of cases, human immunodeficiency virus type 1 (HIV-1) infection is transmitted through sexual intercourse. A single founder virus in the blood of the newly infected donor emerges from a genetic bottleneck, while in rarer instances multiple viruses are responsible for systemic infection. We sought to characterize the sequence diversity at early infection, between two distinct anatomical sites; the female reproductive tract vs. systemic compartment. We recruited 72 women from Uganda and Zimbabwe within seven months of HIV-1 infection. Using next generation deep sequencing, we analyzed the total genetic diversity within the C2-V3-C3 envelope region of HIV-1 isolated from the female genital tract at early infection and compared this to the diversity of HIV-1 in plasma. We then compared intra-patient viral diversity in matched cervical and blood samples with three or seven months post infection. Genetic analysis of the C2-V3-C3 region of HIV-1 env revealed that early HIV-1 isolates within blood displayed a more homogeneous genotype (mean 1.67 clones, range 1-5 clones) than clones in the female genital tract (mean 5.7 clones, range 3-10 clones) (p<0.0001). The higher env diversity observed within the genital tract compared to plasma was independent of HIV-1 subtype (A, C and D). Our analysis of early mucosal infections in women revealed high HIV-1 diversity in the vaginal tract but few transmitted clones in the blood. These novel in vivo finding suggest a possible mucosal sieve effect, leading to the establishment of a homogenous systemic infection.

Traditional healers provide healthcare to a substantial proportion of people living with HIV infection (PLHIV) in high HIV burden countries in sub-Saharan Africa. However, the impact on the health of retained patients visiting traditional healers is unknown. In 2011, a study to asses adherence to anti-retroviral therapy (ART) performed in 18 purposefully selected HIV treatment centers in Tanzania, Zambia and Uganda showed that 'consulting a traditional healer/herbalist because of HIV' was an independent risk factor for incomplete ART adherence. To identify characteristics of PLHIV on ART who were also consulting traditional healers, we conducted a secondary analysis of the data from this study. It was found that 260 (5.8%) of the 4451 patients enrolled in the study had consulted a traditional healer during the last three months because of HIV. In multivariable analysis, patients with fewer HIV symptoms, those who had been on ART for >5.3 years and those from Tanzania were more likely to have consulted a traditional healer. However, at the time of the study, there was a famous healer in Manyara district, Loliondo village of Tanzania who claimed his herbal remedy was able to cure all chronic diseases including HIV. HIV treatment programs should be aware that patients with fewer HIV symptoms, those who have been on ART for five or more years, and patients attending ART centers near famous traditional healers are likely to consult traditional healers. Such patients may need more support or counseling about the risks of both stopping ART and poor adherence. Considering the realities of inadequate human resources for health and the burden of disease caused by HIV in sub-Saharan Africa, facilitating a collaboration between allopathic and traditional health practitioners is recommended.

Introduction: Long-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes., Methods: Newly HIV infected Ugandan and Zimbabwean women (N=303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5years., Results: Ugandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P<0.001), a difference not associated with any other clinical parameters. Relative replicative fitness and entry efficiency of HIV-1 variants directly correlated with virulence in the patients, subtype D>A>C (P<0.001, ANOVA)., Discussion: HIV-1 subtype C was less virulent than either A or D in humans; the latter being the most virulent. Longer periods of asymptomatic HIV-1 subtype C could explain the continued expansion and dominance of subtype C in the global epidemic., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cervicovaginal HIV shedding is associated with increased female-to-male and mother-to-child transmission. Genital inflammation may increase shedding through cytokines/chemokines which recruit and activate HIV target cells. We evaluated whether cervical immune mediators present before seroconversion affected HIV shedding and whether mediators differed between shedders and nonshedders., Methods: We used cervical samples from 187 African women with documented HIV seroconversion in the Hormonal Contraception and HIV study. Samples were from the two visits before seroconversion (T-2 and/or T-1), and/or at seroconversion (T0), and/or the two visits (T + 1 and/or T + 2) after seroconversion. We measured interleukin (IL)-1β, IL-1 Receptor Antagonist (IL-1RA), IL-6, IL-8, RANTES (Regulated on Activation, Normal T-Cell Expressed and Secreted), MIP-3α, vascular endothelial growth factor (VEGF), Intercellular Adhesion Molecule-1 (ICAM-1), secretory leukocyte protease inhibitor (SLPI), and BD-2 and used the Wilcoxon test and generalized linear models to evaluate the association between mediators and shedding., Results: The only immune mediator that differed at T-1 was RANTES, which was higher among shedders (p ≤ .05). HIV seroconversion was followed by significant decreases in many mediators, but a significant increase in RANTES. The magnitude of the change was significantly different for shedders versus nonshedders with regard to RANTES (increased in both groups, significantly more so in shedders), SLPI (decreased in both groups, significantly more so in shedders), and MIP-3α (decreased in shedders and increased in nonshedders). At T0, shedders had lower levels of SLPI and MIP-3α than nonshedders., Conclusions: In this study, a specific immune mediator profile was associated with risk of cervical HIV shedding. Higher and increasing levels of RANTES and lower and decreasing levels of SLPI and MIP-3α were associated with increased risk of HIV shedding.

Objective: To describe pregnancy outcomes among HIV-infected women and examine factors associated with live birth among those receiving and not receiving combination antiretroviral therapy (cART)., Methods: The present analysis included women with HIV from Uganda and Zimbabwe who participated in a prospective cohort study during 2001-2009. Incident pregnancies and pregnancy outcomes were recorded quarterly. The Kaplan-Meier method was used to estimate incident pregnancy probabilities; factors associated with live birth were evaluated by Poisson regression with generalized estimating equations., Results: Among 306 HIV-infected women, there were 160 incident pregnancies (10.1 per 100 women-years). The pregnancy rate was higher among cART-naïve women than among those receiving cART (10.7 vs 5.5 per 100 women-years; P=0.047), and it was higher in Uganda than in Zimbabwe (14.4 vs 7.7 per 100 women-years; P<0.001). Significant associations were noted between a live birth and prenatal care (relative risk 3.9; 95% confidence interval 2.2-6.9) and illness during pregnancy (relative risk 0.8; 95% confidence interval 0.7-1.0)., Conclusion: Women not receiving cART have higher pregnancy rates than do those receiving cART, but cART use might not affect the risk of adverse pregnancy outcomes. Timely prenatal care and monitoring of illnesses during pregnancy should be incorporated into treatment services for HIV-infected women., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Little is known about the differences in clinical manifestations between women with various HIV-1 subtypes during acute (AI) and early (EI) HIV infection. In a longitudinal cohort study, clinical signs and symptoms among Uganda and Zimbabwe women with AI and EI were compared with HIV-negative controls; symptoms were assessed quarterly for 15 to 24 months. Early HIV infection was defined as the first visit during which a woman tested HIV antibody positive. Women who were HIV negative serologically but DNA polymerase chain reaction positive were considered AI. In all, 26 women were classified AI and 192 EI, with 654 HIV-negative controls. Primary HIV infection (AI and EI) was associated with unexplained fever (P <.01), weight loss (P <.01), fatigue (P <.01), inguinal adenopathy (P <.01), and cervical friability (P =.01). More women with subtype C infection had unexplained fever, fatigue, and abnormal vaginal discharge compared to subtype A or D infection. Inguinal adenopathy occurred less often in women with subtype A infection than those with subtype C or D infection., (© The Author(s) 2013.)

Background: Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC., Methods and Findings: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship., Conclusions: This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.

Objective: To evaluate the effect of nevirapine-containing antiretroviral therapy (ART) on combined oral contraceptive (COC) effectiveness., Design: Nonrandomized prospective clinical trial., Methods: We enrolled HIV-infected women aged 18-35 years in South Africa and Uganda who had regular menses, were sexually active, and had no medical contraindications to COC use. We enrolled 196 women taking nevirapine-containing ART and 206 women not yet eligible for ART as a control group. We treated all participants with low-dose COCs. Our main outcomes were ovulation and pregnancy rates. We estimated ovulation in the first two cycles using weekly serum progesterone and tested for pregnancy monthly for 24 weeks., Results: The median age of participants was 29 and their median CD4 cell count was 486. In the ART group, 43 of 168 (26%) ovulated in cycle 1, 30 of 163 (18%) in cycle 2, and 18 of 163 (11%) in both cycles. In the non-ART group, 26 of 168 (16%) ovulated in cycle 1, 31 of 165 (19%) in cycle 2, and 20 of 165 (12%) in both cycles. We found no significant difference in ovulation rates between groups: unadjusted odds ratio 1.36 (95% confidence interval 0.85-2.18). Pregnancy rates also did not differ: 10.0 per 100-women-years in the ART group and 10.1 per 100-women-years in the non-ART group. Self-reported COC adherence, condom use, vaginal bleeding, and adverse events were similar. Five serious adverse events were reported, all in the non-ART group., Conclusion: ART use did not affect risk of ovulation or pregnancy in women taking COCs, suggesting that nevirapine-containing ART does not interfere with COC contraceptive effectiveness.

Background: Hormonal contraception (HC) use by HIV-infected women has been identified by the World Health Organization as an important strategy for reducing vertical HIV transmission. Little is known about the factors associated with HC discontinuation among HIV-infected women., Methods: We analyzed data from a prospective study of HC use among 231 HIV-infected users with oral contraceptive (OC) or injectable depot medroxyprogesterone acetate (DMPA) in Uganda and Zimbabwe. We used Kaplan-Meier survival curves to estimate the median duration of OC and DMPA use and use of any highly effective contraceptive method. Cox proportional hazards models were used to investigate factors associated with HC discontinuation., Results: Median duration was 36 months [95% confidence interval (CI): 14 to 61] for OC use and 19 months (95% CI: 14 to 24) for DMPA use. Median duration of any highly effective method was 36 months (95% CI: 26 to N/A) for OC users and 22 months (95% CI: 14 to 38) for DMPA users. In multivariable analyses, living in Zimbabwe [hazard ratio (HR): 0.39; 95% CI: 0.18 to 0.83], no partner (HR: 7.18; 95% CI: 3.05 to 16.88), and cervical infection (HR: 1.99; 95% CI: 0.90 to 4.41) were associated with OC discontinuation. No partner (HR: 2.00; 95% CI: 1.12 to 3.58), nausea (HR: 1.84; 95% CI: 1.02 to 3.34), and excessive night sweats (HR: 1.80; 95% CI: 0.95 to 3.40) were associated with DMPA discontinuation., Conclusion: Long-term use of HC methods is acceptable to HIV-infected women. Women discontinue for a variety of reasons, primarily unrelated to HIV. Alternative methods and ongoing contraceptive counseling is essential to reduce unplanned pregnancies and vertical HIV transmission.

Objective: Mycoplasma genitalium is an emerging sexually transmitted infection (STI) and has been associated with reproductive tract infections and HIV in cross-sectional studies. In this longitudinal study, we assess whether M. genitalium is associated with risk of acquiring HIV-1 infection., Design: Nested case-control study within a large prospective study in Zimbabwe and Uganda, Methods: A total of 190 women who seroconverted to HIV-1 during follow-up (cases) were matched with up to two HIV-negative controls. Mycoplasma genitalium testing was performed by PCR-ELISA, using archived cervical samples from the HIV-1 detection visit and the last HIV-negative visit for cases, and equivalent visits in follow-up time for controls. Risk factors for HIV-1 acquisition were analyzed using conditional logistic regression, with M. genitalium as the primary exposure., Results: Mycoplasma genitalium was a common infection in these populations (14.8 and 6.5% prevalence among cases and controls, respectively, at the visit prior to HIV-1 detection), and more prevalent than other nonviral STIs. We found a greater than two-fold independent increased risk of HIV-1 acquisition among women infected with M. genitalium at the visit prior to HIV-1 acquisition [adjusted odds ratio (AOR) = 2.42; 95% confidence interval (CI) 1.01-5.80), and at time of HIV-1 acquisition (AOR = 2.18; 95% CI 0.98-4.85). An estimated 8.7% (95% CI 0.1-12.2%) of incident HIV-1 infections were attributable to M. genitalium., Conclusion: This is the first longitudinal study to assess the relationship between M. genitalium and HIV-1 acquisition. If findings from this research are confirmed, M. genitalium screening and treatment among women at high risk for HIV-1 infection may be warranted as part of an HIV-1 prevention strategy.

Background: We examined hormonal contraceptive (HC) discontinuation and factors associated with discontinuation among HIV-uninfected women and the effect of HIV diagnosis on subsequent contraceptive use., Study Design: We analyzed 4461 HIV-uninfected women from a prospective study of HC and HIV acquisition in Uganda, Zimbabwe and Thailand. Participants were ages 18-35 years, not pregnant, and using oral contraceptives (OCs) or injectable depot medroxyprogesterone acetate (DMPA) for at least 3 months before enrollment (median duration of OC and DMPA use before enrollment was 11.7 and 8.9 months, respectively). We compared the probability of OC and DMPA discontinuation using survival analysis and factors related to discontinuation using Cox regression. We also analyzed contraceptive patterns among 194 women who became infected with HIV., Results: Median duration of use after study enrollment was 15.6 months for OCs and 18.5 months for DMPA. Continuation rates for both methods were highest in Thailand. Factors associated with OC discontinuation included, nausea, breast tenderness, condom use, and no sex. Factors associated with DMPA discontinuation included young age, breast tenderness, nausea, irregular bleeding, high-risk sexual behaviors, partner risk, condom use, and no sex. Following an HIV diagnosis, 135 (98.5%) of 137 hormonal users continued HC and 14 (25%) of 57 nonusers began using HC., Conclusions: Contraceptive continuation for OCs and DMPA was relatively high over 2 years. Young women, those reporting side effects, and those using condoms are more likely to discontinue and need ongoing contraceptive counseling. Many women receiving HIV-positive diagnoses desire effective contraception., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity, altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV)., Methods: One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before, at, and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes., Results: We observed ∼5-fold higher odds of multiple (≥2) new HPV detections only after HIV acquisition, relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed ∼2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition, relative to HIV-uninfected women in multivariable models., Conclusions: These findings suggest that HIV infection has an immediate impact on genital tract immunity, as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

Hormonal contraceptives are used widely worldwide; their effect on HIV acquisition remains unresolved. We reanalyzed data from the Hormonal Contraception and HIV Study using marginal structural modeling to reduce selection bias due to time-dependent confounding. Replicating our original analysis closely, we found that depo-medroxyprogesterone acetate (DMPA) but not combined oral contraceptive (COC) was associated with increased HIV acquisition. Also, young (18-24 years) but not older women who used DMPA and COCs were at increased HIV risk.

We conducted a cross-sectional study with 208 HIV-uninfected and 188 HIV-infected women in Uganda and Zimbabwe to investigate differences in median CD4 counts. Absolute CD4 counts were determined by flow cytometry. Multivariate analyses were used to examine the association of country and HIV-infection status on CD4 counts. Median CD4 counts were significantly lower in Zimbabwe than in Uganda overall (649 and 783 cells/mm(3), P = 0.009) and among HIV-infected women (470 and 614 cells/mm(3), P = 0.003). In separate multivariable models, CD4 counts were significantly lower in Zimbabwe in HIV-uninfected (P = 0.014) and infected (P < 0.001) women, controlling for age, contraceptive method, education and living with partner status. In a model combining HIV-uninfected and infected women, there was no significant interaction between country and HIV infection status (P = 0.344), suggesting that the relationship between country and CD4 count was not significantly modified by HIV infection status. This study reinforces the importance of establishing country-specific reference CD4 levels as CD4 count continues to be used as a key biomarker in clinical decision-making for HIV-infected individuals in sub-Saharan Africa.

Objective: : To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbabwean and Ugandan women., Methods: : A multicenter prospective observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Uganda. Participants were interviewed, and tested for HIV and RTIs every 3 months for 15 to 24 months. They received HIV risk reduction counseling, male condoms, and treatment for curable RTIs., Results: : Despite HIV risk reduction counseling and regular screening and treatment for RTIs, the HIV incidence did not decline during the study. Positive HSV-2 serostatus at baseline (hazard ratio [HR] = 3.69, 95% confidence interval = 2.45-5.55), incident HSV-2 (HR = 5.35, 3.06-9.36), incident Neisseria gonorrhoeae (HR = 5.46, 3.41-8.75), and altered vaginal flora during the study (bacterial vaginosis [BV]: HR = 2.12, 1.50-3.01; and intermediate flora: HR = 2.02, 1.39-2.95) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs (Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, and vaginal yeasts). For N. gonorrhoeae, C. trachomatis, T. vaginalis, and vaginal yeasts, the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection. Population attributable risk percent (PAR%) calculations show that HSV-2 contributes most to acquisition of new HIV infections (50.4% for baseline HSV-2 and 7.9% for incident HSV-2), followed by altered vaginal flora (17.2% for bacterial vaginosis and 11.8% for intermediate flora)., Conclusions: : A substantial proportion of new HIV infections in Zimbabwean and Ugandan women are attributable to RTIs, particularly HSV-2 and altered vaginal flora.

Background: Trichomoniasis vaginalis is the most common nonviral sexually transmitted infection (STI) worldwide, with a particularly high prevalence in regions of human immunodeficiency virus (HIV) endemicity. However, its impact as a cofactor for HIV acquisition is poorly understood., Methods: Samples from 213 women who experienced HIV seroconversion (cases) during a longitudinal study involving 4450 women in Uganda and Zimbabwe were matched with samples from HIV-uninfected women (controls). All samples underwent polymerase chain reaction (PCR) analysis for Trichomonas vaginalis DNA. For cases, analyzed samples were from the visit in which HIV seroconversion was detected and the visit preceding detection of seroconversion; for controls, one analyzed sample was from the visit matched by follow-up duration to the cases' seroconversion visit, and the other sample was from the visit immediately preceding the matched visit., Results: The prevalence of T. vaginalis infection before HIV infection was 11.3% in cases and 4.5% in controls (P = .002). In multivariable analysis controlling for hormonal contraception, other STIs, behavioral, and demographic factors, the adjusted odds ratio for HIV acquisition was 2.74 (95% confidence interval, 1.25-6.00) for T. vaginalis-positive cases. The presence of behavioral risk factors for HIV infection, study recruitment from a referral population at high-risk for HIV, primary sex partner-associated risk for HIV infection, and herpes simplex virus type 2 seropositivity were also predictive of incident HIV infection., Conclusions: T. vaginalis infection is strongly associated with an increased risk for HIV infection in this general population of African women. Given the high prevalence of T. vaginalis infection in HIV-endemic areas, T. vaginalis control may have a substantial impact on preventing HIV acquisition among women.

Objective: This study evaluated the effect of the so-called universal placebo compared to the polystyrene sulfonate (PSS) placebo on genital irritation., Design: A single-center, Phase I, randomized, closed-label study was performed to evaluate the genital irritation of microbicide placebo gels. Thirty healthy, sexually abstinent women were randomly assigned to apply 3.5 mL of either the universal placebo or the PSS placebo gel intravaginally twice daily for 14 days., Methods: Genital irritation was assessed by signs as seen on pelvic examination and colposcopy and reports of symptoms. Vaginal health was assessed by wet mounts, Gram stains for Nugent score and polymorphonuclear leukocytes, and semiquantitative vaginal cultures. Acceptability was assessed as reported on the follow-up questionnaire., Results: The universal placebo was less irritating than the PSS placebo with a lower proportion of women experiencing signs and/or symptoms of genital irritation throughout follow-up (36% compared to 80%, p=.0253). The universal placebo was associated with few and mild genital symptoms, few and minor colposcopic findings and good vaginal health with no clinically significant changes in genital flora. Most participants found the feel of the universal placebo gel neutral or pleasant, and all participants found it odorless., Conclusions: The universal placebo appeared safe and acceptable when used twice daily for 14 days. The strategy of creating a de novo inert universal placebo is a successful approach. The universal placebo is appropriate for use as a placebo gel in HIV prevention trials with microbicide candidates.

Objective: To assess whether the risk of complications is higher in HIV-1-infected women compared with non-infected women in the two years following insertion of the intrauterine contraceptive device., Design: Prospective cohort study., Population: Six hundred and forty-nine women (156 HIV-1-infected, 493 non-infected) in Nairobi, Kenya who requested an intrauterine contraceptive device and met local eligibility criteria., Methods: We gathered information on complications related to the use of the intrauterine contraceptive device, including pelvic inflammatory disease, removals due to infection, pain or bleeding, expulsions, and pregnancies at one, four, and 24 months after insertion by study physicians masked to participants' HIV-1 status. Cox regression was used to estimate hazard ratios., Results: Complications were identified in 94 of 636 women returning for follow up (14.7% of HIV-1-infected, 14.8% of non-infected). The incidence of pelvic inflammatory disease was rare in both infected (2.0%) and non-infected (0.4%) groups. Multivariate analyses suggested no association between HIV-1 infection and increased risk of overall complications (hazard ratio = 1.0; 95% CI 0.6-1.6). Infection-related complications (e.g. any pelvic tenderness, removal for infection or pain) were also similar between groups (10.7% of HIV-1-infected, 8.8% of non-infected; P = 0.50), although there was a non-significant increase in infection-related complications among HIV-1-infected women with use of the intrauterine contraceptive device longer than five months (hazard ratio = 1.8; 95% CI 0.8-4.4). Neither overall nor infection-related complications differed by CD4 (immune) status., Conclusions: HIV-1-infected women often have a critical need for safe and effective contraception. The intrauterine contraceptive device may be an appropriate contraceptive method for HIV-1-infected women with ongoing access to medical services.