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Background: Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition. Methods and Findings: We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I² values 0.0%- 16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18-1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00-1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01-1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04-1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p,0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p,0.001), respectively. Conclusions: This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate extended acceptability of vaginal use of a carrageenan-based candidate microbicide and placebo in northern Thai women. Methods: As part of a randomized, placebo-controlled, triple-blinded clinical trial, women were asked to insert gel with each vaginal sex act and at least three times per week for 1 year. Used applicators were collected monthly; acceptability questions were asked quarterly. Results: One hundred sixty-five women were enrolled (83 microbicide, 82 placebo); 148 (90%) remained in the study for 12 months. Gel use was high, with ≥87% returning at least three used applicators per week at each visit. Although acceptability was generally high, some decline in positive reporting was noted in terms of ease of application, timing of gel insertion, and gel volume over time. Approximately one quarter reported gel use increased her sexual pleasure. Over one quarter reported that gel volume of 5 mL was too much. All women with a steady partner at 12 months reported talking to their partner about using the gel. Only 2 women spontaneously mentioned being able to use a product covertly as one of the most appealing attributes of a potential microbicide. Conclusions: Although women in this study generally reported high acceptability and use, some found 5 mL of gel to be too much. Focusing on enhanced sexual pleasure and lubrication may be beneficial for marketing proven microbicides. Development of products will need to balance lubrication and efficacy with perceptions of too much volume. The ability to use a product covertly was not a high priority in this population. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study that assessed the safety and acceptability of the vaginal application of Carraguard, a carrageenan-derived candidate microbicide among women in Thailand. There were no abnormal vaginal flora, Pap smear abnormalities or abnormal genital clinical findings in Carraguard group. Carraguard and placebo group that used methylcellulose gel reported high acceptability.

[This corrects the article DOI: 10.1371/journal.pmed.1002511.]. [ABSTRACT FROM AUTHOR]

Background: Sociodemographic, behavioral and clinical correlates of the vaginal microbiome (VMB) as characterized by molecular methods have not been adequately studied. VMB dominated by bacteria other than lactobacilli may cause inflammation, which may facilitate HIV acquisition and other adverse reproductive health outcomes.Methods: We characterized the VMB of women in Kenya, Rwanda, South Africa and Tanzania (KRST) using a 16S rDNA phylogenetic microarray. Cytokines were quantified in cervicovaginal lavages. Potential sociodemographic, behavioral, and clinical correlates were also evaluated.Results: Three hundred thirteen samples from 230 women were available for analysis. Five VMB clusters were identified: one cluster each dominated by Lactobacillus crispatus (KRST-I) and L. iners (KRST-II), and three clusters not dominated by a single species but containing multiple (facultative) anaerobes (KRST-III/IV/V). Women in clusters KRST-I and II had lower mean concentrations of interleukin (IL)-1α (p < 0.001) and Granulocyte Colony Stimulating Factor (G-CSF) (p = 0.01), but higher concentrations of interferon-γ-induced protein (IP-10) (p < 0.01) than women in clusters KRST-III/IV/V. A lower proportion of women in cluster KRST-I tested positive for bacterial sexually transmitted infections (STIs; ptrend = 0.07) and urinary tract infection (UTI; p = 0.06), and a higher proportion of women in clusters KRST-I and II had vaginal candidiasis (ptrend = 0.09), but these associations did not reach statistical significance. Women who reported unusual vaginal discharge were more likely to belong to clusters KRST-III/IV/V (p = 0.05).Conclusion: Vaginal dysbiosis in African women was significantly associated with vaginal inflammation; the associations with increased prevalence of STIs and UTI, and decreased prevalence of vaginal candidiasis, should be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Dysbiosis of the vaginal microbiome poses a serious risk for sexual human immunodeficiency virus type 1 (HIV-1) transmission. Prevotella spp are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished P timonensis-enhanced infection. Our study shows that the vaginal microbiome directly affects mucosal CD4+ T-cell susceptibility, emphasizing importance of vaginal dysbiosis diagnosis and treatment., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Antimicrobial stewardship interventions mainly focus on initial antibiotic prescriptions, with few considering within-episode repeat prescriptions. We aimed to describe the magnitude, type and determinants of within-episode repeat antibiotic prescriptions in patients presenting to primary care with respiratory tract infections (RTIs)., Methods: We conducted a population-based cohort study among 530 sampled English general practices within the Clinical Practice Research Datalink (CPRD). All individuals with a primary care RTI consultation for which an antibiotic was prescribed between March 2018 and February 2022. Main outcome measurement was repeat antibiotic prescriptions within 28 days of a RTI visit stratified by age (children vs. adults) and RTI type (lower vs. upper RTI). Multivariable logistic regression and principal components analyses were used to identify risk factors and patient clusters at risk for within-episode repeat prescriptions., Findings: 905,964 RTI episodes with at least one antibiotic prescription were identified. In adults, 19.9% (95% CI 19.3-20.5%) had at least one within-episode repeat prescription for a lower RTI, compared to 10.5% (95% CI 10.3-10.8%) for an upper RTI. In children, this was around 10% irrespective of RTI type. The majority of repeat prescriptions occurred a median of 10 days after the initial prescription and was the same antibiotic class in 48.3% of cases. Frequent RTI related GP visits and prior within-RTI-episode repeat antibiotic prescriptions were main factors associated with repeat prescriptions in both adults and children irrespective of RTI type. Young (<2 years) and older (65+) age were associated with repeat prescriptions. Among those aged 2-64 years, allergic rhinitis, COPD and oral corticosteroids were associated with repeat prescriptions., Interpretations: Repeat within-episode antibiotic use accounts for a significant proportion of all antibiotics prescribed for RTIs, with same class antibiotics unlikely to confer clinical benefit and is therefore a prime target for future antimicrobial stewardship interventions., Competing Interests: Declaration of Competing Interest No conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Earlier studies showed that BCG vaccination improves antibody responses of subsequent vaccinations. Similarly, in older volunteers we found an increased IgG receptor-binding domain (RBD) concentration after SARS-CoV-2 infection if they were recently vaccinated with BCG. This study aims to assess the effect of BCG on the serum antibody concentrations induced by COVID-19 vaccination in a population of adults older than 60 years. Serum was collected from 1,555 participants of the BCG-CORONA-ELDERLY trial a year after BCG or placebo, and we analyzed the anti-SARS-CoV-2 antibody concentrations using a fluorescent-microsphere-based multiplex immunoassay. Individuals who received the full primary COVID-19 vaccination series before serum collection and did not test positive for SARS-CoV-2 between inclusion and serum collection were included in analyses (n = 945). We found that BCG vaccination before first COVID-19 vaccine (median 347 days [IQR 329-359]) did not significantly impact the IgG RBD concentration after COVID-19 vaccination in an older European population., Competing Interests: M.N. is scientific founder and on the scientific advisory board of TTxD. J.W. received funding from the Netherlands Organisation for Health Research and Development (ZonMw) for a project entitled “BCG vaccination to minimise COVID-19 disease severity and duration” with project number 10430 01 201 0026. This project is distinct from the project described in the current publication but the investigators of the two projects overlap., (© 2023 The Author(s).)

Objectives: We estimated vaccine effectiveness (VE) of primary and booster vaccinations against SARS-CoV-2 infection overall and in four risk groups defined by age and medical risk condition during the Delta and Omicron BA.1/BA.2 periods., Methods: VAccine Study COvid-19 is an ongoing prospective cohort study among Dutch adults. The primary end point was a self-reported positive SARS-CoV-2 test from July 12, 2021 to June 06, 2022. The analyses included only participants without a previous SARS-CoV-2 infection based on a positive test or serology. We used Cox proportional hazard models with vaccination status as the time-varying exposure and adjustment for age, sex, educational level, and medical risk condition., Results: A total of 37,170 participants (mean age 57 years) were included. In the Delta period, VE <6 weeks after the primary vaccination was 80% (95% confidence interval 69-87) and decreased to 71% (65-77) after 6 months. VE increased to 96% (86-99) shortly after the first booster vaccination. In the Omicron period, these estimates were 46% (22-63), 25% (8-39), and 57% (52-62), respectively. For the Omicron period, an interaction term between vaccination status and risk group significantly improved the model (P <0.001), with generally lower VEs for those with a medical risk condition., Conclusion: Our results show the benefit of booster vaccinations against infection, also in risk groups; although, the additional protection wanes quite rapidly., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess the performances of three commonly used antigen rapid diagnostic tests used as self-tests in asymptomatic individuals in the Omicron period., Methods: We performed a cross-sectional diagnostic test accuracy study in the Omicron period in three public health service COVID-19 test sites in the Netherlands, including 3600 asymptomatic individuals aged ≥ 16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex [Flowflex], MP Biomedicals (MPBio), or Siemens-Healthineers CLINITEST [CLINITEST]) to perform unsupervised at home. Diagnostic accuracies of each self-test were calculated., Results: Overall sensitivities were 27.5% (95% CI, 21.3-34.3%) for Flowflex, 20.9% (13.9-29.4%) for MPBio, and 25.6% (19.1-33.1%) for CLINITEST. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively. Specificities were >99% for all tests in most analyses., Discussion: The sensitivities of three commonly used SARS-CoV-2 antigen rapid diagnostic tests when used as self-tests in asymptomatic individuals in the Omicron period were very low. Antigen rapid diagnostic test self-testing in asymptomatic individuals may only detect a minority of infections at that point in time. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield, and individuals should be advised to re-test when symptoms develop., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic., Methods: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919)., Results: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication., Conclusions: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection., Study Design: Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725)., Results: Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association., Conclusion: We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk., Implications: Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Immune mediated inflammatory diseases (IMIDs) have similarities in pathophysiology and treatment. Not much is known, however, about health-related quality of life (HR-QoL) in IMIDs. We assessed and compared HR-QoL, using the validated EuroQoL 5-dimensions 5-levels questionnaire, in an observational cohort comprising 530 patients (67.5% female, mean age 49 years (95% CI 35.9-50.9), mean disease duration 31.0 months (95% CI 27.2-34.8)), with the following IMIDs: connective tissue diseases (32.6%), uveitis (20.8%), inflammatory arthritis (17.7%), psoriasis (15.5%), vasculitis (6.2%), primary antiphospholipid syndrome (4.2%), and autoinflammatory diseases (2.8%). Patients used either no anti-inflammatory therapy (31.5%), monotherapy (28.7%), or a combination of anti-inflammatory drugs (39.8%). The mean HR-QoL utility score was 0.75 (95% CI 0.72-0.78). Multinominal logistic regression analysis showed a statistically significant association between a very low HR-QoL (utility score (<0.70)) and female sex, rheumatological IMID or psoriasis, smoking or having smoked in the past, and current biological disease modifying anti-rheumatic drugs use., (Copyright © 2020 University Medical Centre Utrecht. Published by Elsevier Inc. All rights reserved.)

Background: Metronidazole is the first-line treatment for bacterial vaginosis, but cure rates are suboptimal and recurrence rates high., Objectives: To evaluate the impact of a standard course of oral metronidazole treatment (500 mg twice per day for 7 days) on the vaginal microbiota of Rwandan bacterial vaginosis patients using microscopy and 16S rRNA gene sequencing, and to evaluate correlates of treatment failure., Study Design: HIV-negative, nonpregnant women aged 18-45 years with bacterial vaginosis and/or Trichomonas vaginalis (N=68) were interviewed and sampled before and after metronidazole treatment. They were also screened, and treated if applicable, for other urogenital infections. The vaginal microbiota was assessed by Gram stain Nugent scoring, Illumina 16S rRNA HiSeq sequencing (relative abundances), and BactQuant 16S gene quantitative polymerase chain reaction (estimated concentrations). Only women with a pretreatment Nugent score of 7-10 and a valid posttreatment Nugent score (N=55) were included in metronidazole treatment failure analyses, with treatment failure defined as a posttreatment Nugent score of 4-10., Results: The bacterial vaginosis cure rate by Nugent scoring was 54.5%. The mean total vaginal bacterial concentration declined from 6.59 to 5.85 log 10 /μL (P<.001), which was mostly due to a reduction in mean bacterial vaginosis-associated anaerobes concentration (all bacterial vaginosis-associated anaerobe taxa combined) from 6.23 to 4.55 log 10 /μL (P<.001). However, only 16.4% of women had a bacterial vaginosis anaerobes concentration reduction of more than 50%, and only 3 women had complete eradication. The mean concentration of lactobacilli (all species combined) increased from 4.98 to 5.56 log 10 /μL (P=.017), with L. iners being the most common species pre- and posttreatment. The mean concentration of pathobionts (defined as Proteobacteria, streptococci, staphylococci, enterococci, and a few others) did not change significantly: from 1.92 log 10 /μL pretreatment to 2.01 log 10 /μL posttreatment (P=.939). Pretreatment pathobionts concentration, and having a pretreatment vaginal microbiota type containing more than 50% Gardnerella vaginalis (compared with less than 50%), were associated with increased likelihood of treatment failure, but the latter did not reach statistical significance (P=.044 and P=.084, respectively)., Conclusions: Metronidazole alone may not cure women with high G. vaginalis relative abundance, potentially due to biofilm presence, and women with high pathobionts concentration. These women may benefit from additional biofilm-disrupting and/or pathobiont-targeting treatments., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Bacterial vaginosis (BV) is a common yet poorly understood vaginal condition that has become a major focus of HIV transmission and immunology research. Varied terminologies are used by clinicians and researchers to describe microbial communities that reside in the female reproductive tract (FRT), which is driven, in part, by microbial genetic and metabolic complexity, evolving diagnostic and molecular techniques, and multidisciplinary perspectives of clinicians, epidemiologists, microbiologists, and immunologists who all appreciate the scientific importance of understanding mechanisms that underlie BV. This Perspectives article aims to clarify the varied terms used to describe the cervicovaginal microbiota and its "nonoptimal" state, under the overarching term of BV. The ultimate goal is to move toward language standardization in future literature that facilitates a better understanding of the impact of BV on FRT immunology and risk of sexually transmitted infections, including HIV.

The most common dysbiosis of the vaginal microbiome (defined here as a vaginal microbiome not dominated by lactobacilli) is bacterial vaginosis, an anaerobic polybacterial dysbiosis. Other dysbiotic states of importance to global health are vaginal microbiota with a high abundance of streptococci, staphylococci or Enterobacteriaceae, vaginal candidiasis and trichomoniasis. Knowledge about the different types of dysbiosis and their relationship to urogenital and reproductive disease burden has increased in recent years by applying non-culture-based techniques, but is far from complete. The burden of bacterial vaginosis is highest in sub-Saharan Africa and in women of sub-Saharan African descent living elsewhere. Vaginal dysbiosis has been associated with increased susceptibility to and transmission of HIV and other sexually transmitted infections and increased risk of pelvic inflammatory disease, preterm birth and maternal and neonatal infections. In this review, we summarize the contribution of vaginal dysbiosis to the global burden of each of these and highlight areas that require more research., (Crown Copyright © 2017. Published by Elsevier Masson SAS. All rights reserved.)

Cervicovaginal microbiota not dominated by lactobacilli may facilitate transmission of HIV and other sexually transmitted infections (STIs), as well as miscarriages, preterm births and sepsis in pregnant women. However, little is known about the exact nature of the microbiological changes that cause these adverse outcomes. In this study, cervical samples of 174 Rwandan female sex workers were analyzed cross-sectionally using a phylogenetic microarray. Furthermore, HIV-1 RNA concentrations were measured in cervicovaginal lavages of 58 HIV-positive women among them. We identified six microbiome clusters, representing a gradient from low semi-quantitative abundance and diversity dominated by Lactobacillus crispatus (cluster R-I, with R denoting 'Rwanda') and L. iners (R-II) to intermediate (R-V) and high abundance and diversity (R-III, R-IV and R-VI) dominated by a mixture of anaerobes, including Gardnerella, Atopobium and Prevotella species. Women in cluster R-I were less likely to have HIV (P=0.03), herpes simplex virus type 2 (HSV-2; P<0.01), and high-risk human papillomavirus (HPV; P<0.01) and had no bacterial STIs (P=0.15). Statistically significant trends in prevalence of viral STIs were found from low prevalence in cluster R-I, to higher prevalence in clusters R-II and R-V, and highest prevalence in clusters R-III/R-IV/R-VI. Furthermore, only 10% of HIV-positive women in clusters R-I/R-II, compared with 40% in cluster R-V, and 42% in clusters R-III/R-IV/R-VI had detectable cervicovaginal HIV-1 RNA (Ptrend=0.03). We conclude that L. crispatus-dominated, and to a lesser extent L. iners-dominated, cervicovaginal microbiota are associated with a lower prevalence of HIV/STIs and a lower likelihood of genital HIV-1 RNA shedding.

Background: The prevalence, incidence and persistence of human papillomavirus (HPV) types in sub-Saharan Africa are not well established. The objectives of the current study are to describe (predictors of) the epidemiology of HPV among high-risk women in Kigali, Rwanda., Methods: HIV-negative, high-risk women were seen quarterly for one year, and once in Year 2. HIV serostatus, clinical, and behavioral information were assessed at each visit, HPV types at Month 6 and Year 2, and other sexually transmitted infections (STI) at selected visits. HPV prevalence was also assessed in HIV-positive, high-risk women., Results: Prevalence of any HPV was 47.0% in HIV-negative women (median age 25 years) compared to 72.2% in HIV-positive women (median age 27 years; OR 2.9, 95% CI 1.9-4.6). Among HIV-negative women, cumulative incidence of high-risk (HR)-HPV was 28.0% and persistence 32.0% after a mean period of 16.6 and 16.9 months, respectively. Prior Chlamydia trachomatis and Neisseria gonorrhoeae infection, concurrent low-risk (LR)-HPV infection and incident HSV-2 were associated with HR-HPV prevalence among HIV-negative women; prior C. trachomatis infection and co-infection with LR-HPV and HPV16-related HPV types with HR-HPV acquisition. HPV16-related types were the most prevalent and persistent., Conclusions: High HPV prevalence, incidence and persistence were found among high-risk women in Kigali. HPV52 had the highest incidence; and, together with HPV33 and HPV58, were strongly associated with acquisition of other HR-HPV types in HIV-negative women.

Objective: To evaluate linkage-to-care, sexual behavior change, and psychosocial experiences among newly HIV-diagnosed female sex workers (FSWs) in Rwanda., Methods: FSWs (n = 800) with unknown serostatus were screened for HIV during 2007/2008. Women testing HIV positive (n = 192) were referred to care and asked to return for interviews and laboratory testing 12-36 months postdiagnosis. One hundred fourty-one women (73%) returned for the postdiagnosis visit., Results: Median CD4 count at diagnosis was 460 cells per microliter [interquartile range (IQR): 308-628], with 32% eligible for antiretroviral therapy (ART) per national CD4 criteria (median CD4: 235, IQR: 152-303). Postdiagnosis, 92% of women reported having disclosed their HIV status to a friend or relative, 85% reported having enrolled in HIV care (median 30 days after diagnosis, IQR: 7-360), including 89% among ART-eligible women. Among ART-eligible women in care, 87% had initiated ART, with a median follow-up CD4 count of 354 cells per microliter (IQR: 213-456). Women who did not initiate ART experienced a 6-month CD4 count change of -14 cells per microliter (IQR: -41 to 13). Three-quarters of women reported reduced sexual risk behavior postdiagnosis, with only 64% continuing to identify as FSWs. However, 53% reported past month condom use only "sometimes.", Conclusions: Timely linkage to care and ART uptake were high in this group of Rwandan FSWs. However, risky sexual behaviors remained common after enrollment in care. HIV-positive FSWs are an important and receptive group for targeted efforts to increase HIV diagnosis and linkage to care/treatment. Once in care, intensified and sustained HIV prevention education is necessary.

Background: HIV incidence estimation is increasingly being incorporated into HIV/AIDS surveillance activities in both resource-rich and developing countries. We conducted a systematic review to assess the availability of HIV incidence data from sub-Saharan Africa., Methods: We examined peer-reviewed articles, conference proceedings and technical reports published from 1987-2008. Incidence estimates were classified by country, year, population group, and estimation method (prospective study or the serologic testing algorithm for recent HIV seroconversion; STARHS)., Results: Our search yielded HIV incidence estimates for 15 of 44 sub-Saharan African countries, with 57 studies generating 264 unique estimates. Of these, 239 (91%) were obtained via prospective studies, and 25 (9%) via the STARHS method (24 using the BED-CEIA assay). Only five countries reported population-based estimates, and less than two-thirds of studies reported risk factor information. STARHS use increased over time, comprising 20% of estimates since 2006. However, studies that compared STARHS estimates with prospectively observed or modeled estimates often found substantial levels of disagreement, with STARHS often overestimating HIV incidence., Conclusions: Population-based HIV incidence estimates and risk factor information in sub-Saharan Africa remain scant but increasingly available. Regional STARHS data suggest a need for further validation prior to widespread use and incorporation into routine surveillance activities. In the meantime, prevalence and behavioral risk factor data remain important for HIV prevention planning.

Objective: To evaluate interrelationships between bacterial vaginosis (BV), vaginal yeast, vaginal practices (cleansing and drying/tightening), mucosal inflammation, and HIV acquisition., Methods: A multicenter, prospective, observational cohort study was conducted, enrolling 4531 HIV-negative women aged 18 to 35 years attending family planning clinics in Zimbabwe and Uganda. Participants were tested for HIV and reproductive tract infections and were interviewed about vaginal practices every 3 months for 15 to 24 months. BV was measured by Gram stain Nugent scoring, vaginal yeast by wet mount, and mucosal inflammation by white blood cells on Gram stain., Results: HIV incidence was 4.12 and 1.53 per 100 woman-years of follow-up in Zimbabwe and Uganda, respectively (a total of 213 incident infections). Women with BV or vaginal yeast were more likely to acquire HIV, especially if the condition was present at the same visit as the new HIV infection and the visit preceding it (hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.68 to 3.72 and HR = 2.97, 95% CI: 1.67 to 5.28 for BV and yeast, respectively). These relationships did not seem to be mediated by mucosal inflammation. Vaginal drying/tightening was associated with HIV acquisition in univariate (HR = 1.49, 95% CI: 1.03 to 2.15) but not multivariate models. Vaginal cleansing was not associated with HIV acquisition., Conclusions: BV and yeast may contribute more to the HIV epidemic than previously thought.

Background: Candidate vaginal microbicides could cause genital irritation, which in turn could facilitate HIV transmission instead of preventing it. While genital epithelial findings are documented in a standardized manner in most microbicide trials, little is known about background rates and predictors for many types of genital findings., Study Design: A secondary analysis was conducted using data from a Phase II expanded safety study of the candidate microbicide Carraguard gel (Population Council, NY, USA) in Thailand. Genital findings were identified by visual inspection of the cervix, vaginal walls and external genitalia during pelvic exams prior to gel use (screening and enrollment) and during gel use (at 2 weeks and Months 1-12). Women were interviewed about potential risk factors for genital findings at every visit and tested routinely for sexually transmitted and vaginal infections., Results: A total of 258 genital findings were identified in 152 woman-years of follow-up. Genital findings were positively associated with older age, increased parity, self-report of genital symptoms, positive HSV-2 serology, bacterial vaginosis by Nugent scoring and the presence of a genital finding at baseline. Furthermore, vaginal findings were positively associated with vaginal practices and yeast infections. Genital findings were negatively associated with use of hormonal contraception, inconsistently associated with frequency of sex and applicator use, and not associated with condom use., Conclusions: Several factors that are common in women of reproductive age account for the background rate of genital epithelial findings in this population.

Objective: To assess the safety of the candidate microbicide Carraguard gel in HIV-positive women and men., Design: A randomized, placebo-controlled, triple-blinded clinical trial of Carraguard gel when applied vaginally once per day for 14 intermenstrual days by sexually abstinent and sexually active HIV-positive women; and when applied directly to the penis once per day for 7 days by sexually abstinent HIV-positive men., Methods: In each cohort (n = 20 per cohort), participants were randomized to Carraguard, methylcellulose placebo, or no product (1:1:1). In addition to traditional microbicide trial safety endpoints, the effects of microbicide use on vaginal shedding of HIV-1 RNA and markers of genital inflammation, epithelial sloughing, and microhemorrhage were also explored., Results: Gel compliance was high in both gel-use groups in the 3 cohorts. Carraguard use was not associated with abnormal genital findings, other abnormal clinical findings, markers of genital inflammation, epithelial sloughing or microhemorrhage, or self-reported symptoms in women and men, or with abnormal vaginal flora or genital shedding of HIV-1 RNA in women. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups., Conclusions: Once-daily use of Carraguard for 7 to 14 days appeared to be safe in HIV-positive women and men.

Objective: To determine the safety and acceptability of vaginal application of Carraguard, a carrageenan-derived candidate microbicide gel., Design: A randomized, placebo-controlled, triple-blinded clinical trial was conducted in Chiang Rai, northern Thailand., Methods: Women were asked to insert one applicator of study gel vaginally at least three times per week (with or without sex) and to use gel with condoms every time they had sex. Safety was assessed by visual inspection of the vagina and cervix, changes in vaginal flora and self-reported symptoms at day 14, month 1 and then monthly for up to 1 year. Acceptability was assessed through reported use of the gel, return of used and unused applicators, and quarterly interviews., Results: One hundred sixty-five women were randomized: 83 to Carraguard and 82 to the placebo (methylcellulose gel) group. Study gel use was similarly high in both groups throughout the trial with an average of four applicators per week. Carraguard use was not associated with abnormal genital clinical findings, abnormal vaginal flora, Pap smear abnormalities or other abnormal clinical signs or symptoms. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. Participants in both groups reported high acceptability., Conclusions: Carraguard can safely be used an average of four times per week with or without sex and is acceptable to Thai women. A Phase III efficacy trial of Carraguard is warranted and is currently ongoing in South Africa.

Background: Notifying and treating sexual partners of women or men diagnosed with a sexually transmitted infection (STI) is imperative to reducing STI transmission., Methods: As part of a study to examine the introduction of home-based STI testing and rapid-point-of-care diagnostics in a low income population of women in São Paulo, Brazil, we offered 108 women diagnosed with an STI the opportunity to contact partner(s) herself have a clinician contact partner(s) or provide her with medication for partner(s)., Results: Offering partner-delivered medication to women with gonorrhea, chlamydia and/or trichomoniasis, in addition to the standard referral strategies, resulted in high rates of partner treatment, with 80 percent of reported male partners and 96 percent of notified male partners treated. Type of partnership strongly predicted whether the partner was successfully treated. More than half of women interviewed reported partner-delivered medication as their first choice for partner notification in the future., Conclusion: As diagnostic capability for STIs improves in Brazil and other Latin America countries, offering expanded options for partner notification will be an important tool to reduce infection rates. Partner-delivered therapy should be prioritized as it increases the number of partners treated. Introduction of this method will require discussions with providers to remove potential barriers to implementation.