Search

Background: Bacterial vaginosis (BV) is a common cause of vaginitis and, for unknown reasons, is common in lesbian and bisexual women. We defined risks for prevalent BV in lesbian and bisexual women with attention to detailed sexual risk history.Methods: Women 16 to 35 years reporting sex with > or = 1 woman in prior year underwent computer-assisted self-interview with extensive sexual and medical history. BV was defined by Amsel criteria, and associations with subject characteristics were estimated by Poisson regression and generalized estimating equation to adjust for potential coenrollment of current sexual partners.Results: Of 335 participants (median age, 25 years; 22% nonwhite race), 6% reported douching, 24% sex with men, and 91% any sex in the prior 3 months. 96 (29%) had BV, 40% of whom reported corresponding symptoms. BV was associated with reporting a partner with BV (39% vs. 12%; multivariate relative risk [MRR], 4.53 [2.59 -7.93]), vaginal lubricant use (59% vs. 21%; MRR, 1.86 [0.94 -3.68]), or sharing vaginal sex toys in prior 3 months (33% vs. 21%; MRR, 1.70 [0.96 -3.01]). No association was seen for age, race, smoking, hormone use, douching, vaginal, anal or oral sex, or numbers of new partners. Lubricant use and shared vaginal toys were correlated (Spearman 0.29).Conclusions: BV is associated with practices that efficiently transmit vaginal fluid and with use of vaginal lubricant; since these are correlated, assessing independent effects will require further analysis. More research is required to understand relationships between role of transmission of BV-associated bacteria and vaginal lubricant on BV pathogenesis. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The purpose of this study was to examine frequency of and attitudes toward Papanicolaou (Pap) test screening in women who have sex with women (WSW) and to determine prevalence of genital human papillomavirus (HPV). METHODS: Women were eligible if they reported having engaged in sex with another woman in the preceding year Medical and sexual histories were obtained. Cervical specimens for Pap tests and cervical and vaginal specimens for HPV DNA testing were collected. RESULTS: HPV DNA was detected in 31 of 248 WSW (13%). Women who had never had sex with men were less likely to have undergone pelvic examinations and had fewer recent Pap tests. Reasons for not undergoing Pap tests included lack of insurance, previous adverse experiences, and belief that Pap tests were unnecessary. CONCLUSIONS: Despite the occurrence of genital HPV, WSW do not receive adequate Pap test screening. Pap test screening recommendations should not differ for WSW, regardless of sexual history with men. [ABSTRACT FROM AUTHOR]

Background and Objectives: Detection of subclinical Chlamydia trachomatis infection in women is a high but costly public health priority.Goals: To develop and test simple selective screening criteria for chlamydia in women, to assess the contribution of cervicitis to screening criteria, and to evaluate cost-effectiveness of selective versus universal screening.Study Design: Cross-sectional study and cost-effectiveness analysis of 11,141 family planning (FP) and 19,884 sexually transmitted diseases (STD) female clients in Washington, Oregon, Alaska, and Idaho who were universally tested for chlamydia using cell culture, direct fluorescent antibody, enzyme immunoassay, or DNA probe.Results: Prevalence of cervical chlamydial infection was 6.6%. Age younger than 20 years, signs of cervicitis, and report of new sex partner, two or more partners, or symptomatic partner were independent predictors of infection. Selective screening criteria consisting of age 20 years or younger or any partner-related risk detected 74% of infections in FP clients and 94% in STD clients, and required testing 53% of FP and 77% of STD clients. Including cervicitis in the screening criteria did not substantially improve their performance. Universal screening was more cost-effective than selective screening at chlamydia prevalences greater than 3.1% in FP clients and greater than 7% in STD clients.Conclusions: Age and behavioral history are as sensitive in predicting chlamydial infection as criteria that include cervicitis. Cost-effectiveness of selective screening is strongly influenced by the criteria's sensitivity in predicting infection, which was significantly higher in STD clients. At the chlamydia prevalences in the populations studied, it would be cost saving to screen universally in FP clinics and selectively in STD clinics, the reverse of current practice in many locales. [ABSTRACT FROM AUTHOR]

The diagnosis is tricky: You need to exclude other causes of abdominal pain and be keenly aware of the medical, sexual, and contraceptive factors that increase a woman's risk. [ABSTRACT FROM AUTHOR]

Background: Bacterial vaginosis affects millions of women and is associated with several serious health conditions. The cause of bacterial vaginosis remains poorly understood despite numerous studies based on cultures. Bacteria in microbial communities can be identified without cultivation by characterizing their ribosomal DNA (rDNA) sequences.Methods: We identified bacteria in samples of vaginal fluid with a combination of broad-range polymerase-chain-reaction (PCR) amplification of 16S rDNA with clone analysis, bacterium-specific PCR assay of 16S rDNA, and fluorescence in situ hybridization (FISH) performed directly on vaginal fluid from 27 subjects with bacterial vaginosis and 46 without the condition. Twenty-one subjects were studied with the use of broad-range PCR of 16S rDNA, and 73 subjects were studied with the use of bacterium-specific PCR.Results: Women without bacterial vaginosis had 1 to 6 vaginal bacterial species (phylotypes) in each sample (mean, 3.3), as detected by broad-range PCR of 16S rDNA, and lactobacillus species were the predominant bacteria noted (83 to 100 percent of clones). Women with bacterial vaginosis had greater bacterial diversity (P<0.001), with 9 to 17 phylotypes (mean, 12.6) detected per sample and newly recognized species present in 32 to 89 percent of clones per sample library (mean, 58 percent). Thirty-five unique bacterial species were detected in the women with bacterial vaginosis, including several species with no close cultivated relatives. Bacterium-specific PCR assays showed that several bacteria that had not been previously described were highly prevalent in subjects with bacterial vaginosis but rare in healthy controls. FISH confirmed that newly recognized bacteria detected by PCR corresponded to specific bacterial morphotypes visible in vaginal fluid.Conclusions: Women with bacterial vaginosis have complex vaginal infections with many newly recognized species, including three bacteria in the Clostridiales order that were highly specific for bacterial vaginosis. [ABSTRACT FROM AUTHOR]

Background: Few investigations have assessed contributions of both vaginal bacteria and proinflammatory immune mediators to human immunodeficiency virus (HIV) acquisition risk in a prospective cohort., Methods: We conducted a nested case-control study of African women who participated in a randomized placebo-controlled trial of daily oral versus vaginal tenofovir-based preexposure prophylaxis for HIV infection. Vaginal concentrations of 23 bacterial taxa and 16 immune mediators were measured. Relationships between individual bacterial concentrations or immune mediators and HIV risk were analyzed using generalized estimating equations in a multivariable model. Factor analysis assessed relationships between combinations of bacterial taxa, immune mediators, and HIV acquisition risk., Results: We identified 177 HIV pre-seroconversion visits from 150 women who acquired HIV and 531 visits from 436 women who remained HIV uninfected. Fourteen bacterial taxa and 6 proinflammatory cytokines and chemokines were individually associated with greater HIV risk after adjusting for confounders. Women with all 14 taxa versus <14 taxa (adjusted odds ratio [aOR], 4.45 [95% confidence interval {CI}, 2.20-8.98]; P < .001) or all 6 immune mediators versus <6 mediators (aOR, 1.77 [95% CI, 1.24-2.52]; P < .001) had greater risk for HIV acquisition. Factor analysis demonstrated that a bacterial factor comprised of 14 high-risk bacterial taxa (aOR, 1.57 [95% CI, 1.27-1.93]; P < 0.001) and the interferon gamma-induced protein 10 (highest quartile: aOR, 3.19 [95% CI, 1.32-7.72]; P = 0.002) contributed to the highest HIV risk., Conclusions: Bacterial and host biomarkers for predicting HIV acquisition risk identify women at greatest risk for HIV infection and can focus prevention efforts., Competing Interests: Potential conflicts of interest. D. N. F. and T. L. F. receive royalties from Becton Dickinson. S. S. has received speaking honoraria from Lupin Inc. S. S. and D. N. F. have developed intellectual property around the molecular detection of bacteria associated with HIV risk. During the course of this study, S. L. H. received consulting fees from Dare Biosciences and Lupin Inc, and her institution received support from Dickinson, Lupin, Dare, and Curetek. B. A. R. has received payment from Gilead Sciences Inc for service as a data and safety monitoring board member for previous and ongoing clinical trials. All other authors report no potential conflicts. 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. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Safer conception strategies can minimize HIV acquisition during periconception periods among women living in HIV-endemic areas. We examined uptake and predictors of persistent use of the same safer conception strategy among a cohort of HIV-uninfected South African women ages 18-35 years planning for pregnancy with a partner living with HIV or of unknown HIV-serostatus. The safer conception strategies we evaluated included oral PrEP, condomless sex limited to peak fertility, and waiting for a better time to have a child (until, for example, the risks of HIV acquisition are reduced and/or the individual is prepared to care for a child); persistence was defined as using the same safer conception strategy from the first visit through 9 months follow-up. Modified Poisson regression models were used to examine predictors of persistent use of the same strategy. The average age of 227 women in our cohort was 24.6 (range: 18.0, 35.7) years. In this cohort, 121 (74.2%) women reported persisting in the same strategy through 9 months. Employment and HIV knowledge were associated with the persistent use of any strategy. Our results highlight the need to provide safer conception services to women exposed to HIV during periconception periods. Findings also offer some insights into factors that might influence persistent use. Further research is needed to better understand how to involve male partners and how their involvement might influence women's consistent use of safer conception strategies during periconception periods., (© 2024. The Author(s).)

Competing Interests: Conflict of Interest and Sources of Funding: None declared.

Background: Integrating sexually transmitted infection (STI) and preexposure prophylaxis (PrEP) care may optimize sexual and reproductive health., Methods: We nested an STI substudy within a human immunodeficiency virus (HIV) prevention cohort (parent study) of 18- to 35-year-old women from South Africa, planning pregnancy with a partner with HIV or of unknown serostatus. Parent-study women completed annual surveys regarding HIV-risk perceptions and were offered oral PrEP. Preexposure prophylaxis initiators completed quarterly plasma tenofovir (TFV) testing. Substudy women completed STI screening at enrollment, 6 months, onset of pregnancy, and in the third trimester via examination, vaginal swabs tested via PCR for Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Mycoplasma genitalium , and blood tested for Treponema pallidum . Follow-up was 6 months. Women with STIs were treated, offered partner notification (PN) cards, and surveyed regarding PN practices. We describe STI prevalence and incidence, and model factors associated with prevalent infection. Sexually transmitted infection substudy and parent study-only participants were matched on age and number of days on study to assess HIV-risk perception scores between the 2 groups and the proportion with detectable TFV., Results: Among 50 substudy participants, 15 (30%) had prevalent STI. All 13 completing follow-up reported PN. Most did not prefer assisted PN. Mean HIV risk perception scores and proportion with detected plasma TFV were similar across groups., Conclusions: High STI prevalence supports the importance of laboratory screening to optimize sexual health for women planning pregnancy. Rates of self-reported PN are reassuring; low interest in assisted PN suggests the need for alternative approaches. Enhanced STI care did not affect HIV-risk perception or PrEP adherence, however both were relatively high in this cohort., Competing Interests: Conflict of interest: Gilead Sciences provided operational support and study drug for the parent study., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention., Methods and Findings: We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure ("high" adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as "high." Women who became pregnant were initially exited from the cohort by design; from March 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group., Conclusions: Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care., Trial Registration: ClinicalTrials.gov Identifier: NCT03832530 https://clinicaltrials.gov/ct2/show/NCT03832530?term=lynn+matthews&cond=hiv&cntry=UG&draw=2&rank=1., Competing Interests: LTM has received clinical research funding from Gilead Sciences. CWH has received clinical research funding from Gilead Sciences and Merck and, holds patents related to HIV prevention products licensed by Johns Hopkins to Prionde Biopharma, LLC, which he founded. PLA has received consultant fees from Merck, ViiV, and Gilead and research support from Gilead. JEH has received consultant fees from Merck and Natera. KEH is an employee and a shareholder of NoviSci/Target RWE, which has received fees from Janssen Research & Development (Janssen R&D) and Amgen Inc. outside the submitted work., (Copyright: © 2023 Matthews et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study explored the intersecting forms of stigma experienced by HIV-serodifferent couples with unmet reproductive goals in rural Uganda. The parent mixed-methods study, which included 131 HIV-exposed women with plans for pregnancy, offered comprehensive HIV prevention counselling and care over a nine-month period. In-depth interviews were conducted with 37 women and seven male partners to explore care experiences and the use of safer conception strategies. This secondary analysis explored how challenges conceiving informed pregnancy plans and HIV prevention behaviours. The following themes were developed (1) partnership conflicts arise from HIV- and infertility-related forms of stigma, contributing to gender-based violence, partnership dissolution and the pursuit of new partners; (2) cultural and gender norms pressure men and women to conceive and maintain partnerships, which is complicated by the stigma directed towards serodifferent couples; (3) frustration with low partner participation in safer conception strategies led to the decreased use of these methods of HIV prevention; (4) health care provider support promotes continued hope of conception and helps overcome stigma. In HIV-affected partnerships, these intersecting forms of stigma may impact HIV prevention. Seeking to fulfil their reproductive needs, partners may increase HIV transmission opportunities as they engage in condomless sex with additional partners and decrease adherence to prevention strategies. Future research programmes should consider the integration of fertility counselling with reproductive and sexual health care.

After the legalisation of abortion in the USA in 1973, the risk of infectious morbidity and mortality from this procedure notably decreased. With increasingly restrictive legislation targeting access to safe abortion services, reviewing infectious complications of unsafe pregnancy termination is crucial, particularly the diagnosis and management of life-threatening clostridial (and related anaerobic bacterial) infections that can complicate unsafe abortion. This Review deals with two especially devastating infections that are well-documented causes of septic abortion: the anaerobic, spore-forming pathogens Clostridium perfringens and Paeniclostridium sordellii. We seek to familiarise the reader with these bacteria, the clinical syndromes they can cause (with a focus on toxic shock syndrome), and provide a review of diagnosis and treatment options., Competing Interests: Declaration of interests DMA and JMM have had funding for unrelated research from the National Institutes of Health., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Highly efficacious oral pre-exposure prophylaxis (PrEP) is the global standard for human immunodeficiency virus (HIV)-1 prevention, including in clinical trials of novel PrEP agents using active-comparator designs. The analysis assessed whether incident sexually transmitted infections (STIs) can serve as a surrogate indicator of HIV-1 incidence that might occur in the absence of PrEP., Methods: We analyzed data from 3256 women randomized to placebo groups of oral and vaginal PrEP trials (MTN-003/VOICE and MTN-020/ASPIRE). Regression modeling assessed the correlation between incident individual STIs (Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, each considered separately) and incident HIV-1., Results: Across 18 sites in 4 countries (Malawi, South Africa, Uganda, Zimbabwe), STI and HIV-1 incidences were high: HIV-1 4.9, N gonorrhoeae 5.3, C trachomatis 14.5, and T vaginalis 7.1 per 100 person-years. There was limited correlation between HIV-1 incidence and incidence of individual STIs: N gonorrhoeae (r = 0.02, P = .871), C trachomatis (r = 0.49, P = <.001), and T vaginalis (r = 0.10, P = .481). The modest association with C trachomatis was driven by country-level differences in both C trachomatis and HIV-1, with no statistically significant association within countries., Conclusions: Sexually transmitted infection incidence did not reliably predict HIV-1 incidence at the population level among at-risk African women participating in 2 large PrEP trials., 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We provided sexually transmitted infection (STI) screening and facilitated partner notification and treatment among women participating in a periconception HIV prevention program in southwestern Uganda to understand follow-up STI incidence., Methods: Women at-risk for HIV exposure while planning for pregnancy completed laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis at enrollment and 6 months of follow-up and/or incident pregnancy; facilitated partner notification and treatment were offered for those with positive tests. We performed a logistic regression to determine correlates of follow-up STI., Results: Ninety-four participants completed enrollment STI screening with a median age of 29 (IQR 26-34); 23 (24%) had ≥1 STI. Of the 23 participants with enrollment STI(s), all completed treatment and 19 (83%) returned for follow-up; 18 (78%) reported delivering partner notification cards and discussing STIs with partner(s), and 14 (61%) reported all partners received STI treatment. Of the 81 (86%) who successfully completed follow-up STI screening, 17 (21%) had ≥1 STI. The STI incidence rate was 29.0 per 100 person-years. In univariable regression analysis, enrollment STI, younger age, less education, and alcohol consumption were all significantly associated with follow-up STI., Conclusions: We demonstrated high enrollment and follow-up STI rates and moderate participant-reported partner treatment among women planning for pregnancy in Uganda despite partner notification and treatment. Novel STI partner notification and treatment interventions are needed to decrease the STI burden, especially among women planning for and with pregnancy.

Women are disproportionately affected by sexually transmitted infections (STIs) throughout life. In addition to their high prevalence in women, STIs have debilitating effects on female reproductive health due to female urogenital anatomy, socio-cultural and economic factors. In this Review, we discuss the prevalence and impact of non-HIV bacterial, viral and parasitic STIs on the reproductive and sexual health of cisgender women worldwide. We analyse factors affecting STI prevalence among transgender women and women in low-income settings, and describe the specific challenges and barriers to improved sexual health faced by these population groups. We also synthesize the latest advances in diagnosis, treatment and prevention of STIs., (© 2022. Springer Nature Limited.)

Background: Bacterial vaginosis (BV) is a common cause of vaginal discharge and associated with vaginal acquisition of BV-associated bacteria (BVAB)., Methods: We used quantitative polymerase chain reaction assays to determine whether presence or concentrations of BVAB in the mouth, anus, vagina, or labia before BV predict risk of incident BV in 72 women who have sex with men., Results: Baseline vaginal and extra-vaginal colonization with Gardnerella spp, Megasphaera spp, Sneathia spp, BVAB-2, Dialister sp type 2, and other BVAB was more common among subjects with incident BV., Conclusions: Prior colonization with BVAB is a consistent risk for BV., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objective: Vaccine-preventable human papillomavirus (HPV) infection is common, especially in sub-Saharan Africa where HIV risk is also high. However, unlike other sexually transmitted infections (STIs), HPV's role in HIV acquisition is unclear. We evaluated this relationship using data from MTN-003, a clinical trial of HIV chemoprophylaxis among cisgender women in sub-Saharan Africa., Design: A case-control study., Methods: We matched 138 women who acquired HIV (cases) to 412 HIV-negative controls. Cervicovaginal swabs collected within 6 months before HIV seroconversion were tested for HPV DNA. We estimated the associations between carcinogenic (high-risk) and low-risk HPV types and types targeted by HPV vaccines and HIV acquisition, using conditional logistic regression models adjusted for time-varying sexual behaviors and other STIs., Results: Mean age was 23 (±4) years. Any, high-risk and low-risk HPV was detected in 84, 74 and 66% of cases, and 65, 55 and 48% of controls. Infection with at least two HPV types was common in cases (67%) and controls (49%), as was infection with nonavalent vaccine-targeted types (60 and 42%). HIV acquisition increased with any [adjusted odds ratio (aOR) 2.5, 95% confidence interval (95% CI) 1.3-4.7], high-risk (aOR 2.6, 95% CI 1.5-4.6) and low-risk (aOR 1.8, 95% CI 1.1-2.9) HPV. Each additional type detected increased HIV risk by 20% (aOR 1.2, 95% CI 1.1-1.4). HIV acquisition was associated with HPV types targeted by the nonavalent (aOR 2.1, 95% CI 1.3-3.6) and quadrivalent vaccines (aOR 1.9, 95% CI 1.1-3.2)., Conclusion: HPV infection is associated with HIV acquisition in sub-Saharan African women. In addition to preventing HPV-associated cancers, increasing HPV vaccination coverage could potentially reduce HIV incidence., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We describe the impact of universal masking and universal testing at admission on high-risk exposures to severe acute respiratory syndrome coronavirus 2 for healthcare workers. Universal masking decreased the rate of high-risk exposures per patient-day by 68%, and universal testing further decreased those exposures by 77%., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose of Review: This review highlights the intersection of the COVID-19, HIV, and STI pandemics and examines how harm reduction strategies can be applied broadly to controlling a pandemic., Recent Findings: Since the onset of the COVID-19 pandemic, remarkable advances in the understanding of COVID-19 prevention, diagnosis, and treatment have been made at a much faster pace than prior pandemics, yet much more still remains to be discovered. Many of the strategies to control the COVID-19 pandemic mirror those employed to stem the HIV pandemic. Harm reduction principles used in the HIV pandemic can be applied to reduce the morbidity and mortality of the COVID-19 pandemic through effective prevention, detection, and treatment strategies., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Introduction: Whether intramuscular depot medroxyprogesterone acetate (DMPA-IM) and norethisterone enanthate (NET-EN) have a differential impact on the incidence of sexually transmitted infection (STI) remains unclear. In the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, HIV-1 acquisition was higher for DMPA-IM users vs. NET-EN users. We compared DMPA-IM and NET-EN users with regard to chlamydia, gonorrhea, trichomoniasis, syphilis, and herpes simplex virus type 2 (HSV-2) infection., Materials and Methods: Prospective data were analyzed from VOICE, a randomized trial of HIV-1 chemoprophylaxis. Participants were evaluated annually and as indicated for chlamydia, gonorrhea, trichomoniasis, and syphilis. Stored specimens were tested for HSV-2. Proportional hazards models compared the risk of STI between DMPA-IM and NET-EN users., Results: Among 2,911 injectable contraception users in South Africa, 1,800 (61.8%) used DMPA-IM and 1,111 used NET-EN (38.2%). DMPA-IM and NET-EN users did not differ in baseline chlamydia: 15.1 vs. 14.3%, p = 0.54; gonorrhea: 3.4 vs. 3.7%, p = 0.70; trichomoniasis: 5.7 vs.5.0%, p = 0.40; or syphilis: 1.5 vs. 0.7%, p = 0.08; but differed for baseline HSV-2: (51.3 vs. 38.6%, p < 0.001). Four hundred forty-eight incident chlamydia, 103 gonorrhea, 150 trichomonas, 17 syphilis, and 48 HSV-2 infections were detected over 2,742, 2,742, 2,783, 2,945, and 756 person-years (py), respectively (chlamydia 16.3/100 py; gonorrhea 3.8/100 py; trichomoniasis 5.4/100 py; syphilis 0.6/100 py; HSV-2 6.4/100 py). Comparing DMPA-IM with NET-EN users, no difference was noted in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV2 infections, including when adjusted for confounders [chlamydia (aHR 1.03, 95% CI 0.85-1.25), gonorrhea (aHR 0.88, 95% CI 0.60-1.31), trichomoniasis (aHR 1.07, 95% CI 0.74-1.54), syphilis (aHR 0.41, 95% CI 0.15-1.10), and HSV-2 (aHR 0.83, 95% CI 0.45-1.54, p = 0.56)]., Discussion: Among South African participants enrolled in VOICE, DMPA-IM and NETEN users differed in prevalence of HSV-2 at baseline but did not differ in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV-2 infection. Differential HIV-1 acquisition, previously demonstrated in this cohort, does not appear to be explained by differential STI acquisition. However, the high incidence of multiple STIs reinforces the need to accelerate access to comprehensive sexual and reproductive health services., Competing Interests: Conflict of Interest: TP-P is the co-editor of the ‘Integration of HIV Prevention with Sexual and Reproductive Health Services’ special issue to which this manuscript is submitted. 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.

Unique compositional and functional features of the cervicovaginal microbiota have been associated with protection against and risk for sexually transmitted infections (STI). In men, our knowledge of the interaction between the penile microbiota and STI is less developed. The current state of our understanding of these microbiota and their role in select STIs is briefly reviewed, along with strategies that leverage existing findings to manipulate genital microbiota and optimize protection against STIs. Finally, we focus on major research gaps and present a framework for future studies., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Bacterial vaginosis (BV) is a vaginal dysbiotic condition linked to negative gynecological and reproductive sequelae. Flagellated bacteria have been identified in women with BV, including Mobiluncus spp. and BV-associated bacterium-1 (BVAB1), an uncultivated, putatively flagellated species. The host response to flagellin mediated through Toll-like receptor 5 (TLR5) has not been explored in BV. Using independent discovery and validation cohorts, we examined the hypothesis that TLR5 deficiency-defined by a dominant negative stop codon polymorphism, rs5744168-is associated with an increased risk for BV and increased colonization with flagellated bacteria associated with BV (BVAB1, Mobiluncus curtisii , and Mobiluncus mulieris ). TLR5 deficiency was not associated with BV status, and TLR5-deficient women had decreased colonization with BVAB1 in both cohorts. We stimulated HEK-hTLR5-overexpressing NF-κB reporter cells with whole, heat-killed M. mulieris or M. curtisii and with partially purified flagellin from these species; as BVAB1 is uncultivated, we used cervicovaginal lavage (CVL) fluid supernatant from women colonized with BVAB1 for stimulation. While heat-killed M. mulieris and CVL fluid from women colonized with BVAB1 stimulate a TLR5-mediated response, heat-killed M. curtisii did not. In contrast, partially purified flagellin from both Mobiluncus species stimulated a TLR5-mediated response in vitro We observed no correlation between vaginal interleukin 8 (IL-8) and flagellated BVAB concentrations among TLR5-sufficient women. Interspecies variation in accessibility of flagellin recognition domains may be responsible for these observations, as reflected in the potentially novel flagellin products encoded by Mobiluncus species versus those encoded by BVAB1., (Copyright © 2021 dela Cruz et al.)

Background: Knowledge of sexually transmitted infection (STI) prevalence and risk factors is important to the development of tenofovir-based preexposure prophylaxis (PrEP) and safer conception programming. We introduced STI screening among women at risk for HIV exposure who were participating in a safer conception study in southwestern Uganda., Methods: We enrolled 131 HIV-uninfected women, planning for pregnancy with a partner living with HIV or of unknown HIV serostatus (2018-2019). Women were offered comprehensive safer conception counseling, including PrEP. Participants completed interviewer-administered questionnaires detailing sociodemographics and sexual history. We integrated laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis as a substudy to assess STI prevalence. Multivariable logistic regression was used to determine correlates., Results: Ninety-four women completed STI screening (72% of enrolled). Median age was 30 (interquartile range, 26-34) years, and 94% chose PrEP as part of safer conception care. Overall, 24% had STIs: 13% chlamydia, 2% gonorrhea, 6% trichomoniasis, 6% syphilis, and 3% ≥2 STI. Sexually transmitted infection prevalence was associated with younger age (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.77-0.99), prior stillbirth (AOR, 5.04; 95% CI, 1.12-22.54), and not feeling vulnerable to HIV (AOR, 16.33; 95% CI, 1.12-237.94)., Conclusions: We describe a 24% curable STI prevalence among women at risk for HIV exposure who were planning for pregnancy. These data highlight the importance of integrating laboratory-based STI screening into safer conception programs to maximize the health of HIV-affected women, children, and families.

Background: With increasing rates of sexually transmitted infections in the United States, there is a critical need to educate health professionals on the prevention, diagnosis, and treatment of sexually transmitted infections. The National Sexually Transmitted Disease Curriculum (NSTDC, https://www.std.uw.edu) is a free, online curriculum, funded by the Centers for Disease Control and Prevention. The purpose of this article is to evaluate the reach, utilization, and engagement of users with the curriculum., Methods: Data on NSTDC utilization was collected for 24 months after the February 1, 2017 launch. For all users, Google Analytics was used to determine total number of users, geographic location, age and sex, and average session duration. For registered users, additional data analysis included work-role, demographics, and completion of self-study modules, check-on-learning questions, and question banks. User satisfaction was measured on a 5-point Likert scale., Results: During the evaluation period, 136,270 individual users accessed the NSTDC, including 24,652 registered users. Among all registered users, 10,660 (43.2%) were registered nurses, 2810 (11.4%) physicians, 4942 (20.1%) Advanced Practice Nurses and Physician Assistants, and 6213 (25.2%) nonclinicians. Among registered users, 18,533 (75.2%) completed at least 1 module, 7898 (32.0%) completed all 7 modules, and 19,804 (80.4%) answered optional check-on-learning questions. Median satisfaction with the content was (5) very satisfied (interquartile range, 4-5)., Conclusions: The NSTDC is a free, guideline-based, online curriculum with novel dual functionality that has achieved extensive reach with a broad array of health professionals who engage deeply with the material. The wide usage of NSTDC demonstrates the need for high-quality, unbiased, free content in user-focused formats.

Background: Genital infection with herpes simplex virus type 2 (HSV-2) is common and increases risk of human immunodeficiency virus (HIV) transmission and acquisition. Pericoital use of tenofovir (TFV) gel provided protection from HSV-2 acquisition in the CAPRISA 004 study., Methods: We measured estimate of effect of vaginal TFV 1% gel in preventing HSV-2 acquisition among women in VOICE, randomized, double-blinded, placebo-controlled trial assessing daily use of oral and vaginal TFV for HIV-1 preexposure prophylaxis. The TFV level in plasma at the first quarterly visit was used as a measure of gel use., Results: Of 566 participants at risk for HSV-2 acquisition, 532 (94%) had first-quarter plasma TFV and end-of-study HSV-2 serologic data available. Over a follow-up period of 501 person-years, 92 incident cases of HSV-2 acquisition occurred: 77 were in women with no TFV detected in plasma, and 15 occurred in women with TFV detected in plasma (incidence, 20.6 cases/100 person-years [95% confidence interval [CI], 16.2-25.7] vs 11.9 cases/100 person-years [95% CI, 6.6-19.6], respectively). TFV detection in plasma was associated with a trend toward a reduced risk of HSV-2 seroconversion, with an unadjusted hazard ratio (HR) of 0.59 (95% CI, .34-1.02; P = .060) and a HR adjusted for site, age, having ≥2 male sex partners in the past 3 months, use of hormonal contraception, having anal sex in the past 3 months, and HIV status of 0.60 (95% CI, .33-1.08; P = .086)., Conclusions: Detection of TFV in plasma among TFV gel users was associated with a trend toward a reduced risk of HSV-2 acquisition, after controlling for sexual behavior and HIV-1 acquisition., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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.

Background: Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) present serious reproductive health risks and management challenges, with poor control attributed to survival of treatment-resistant biofilm communities. Boric acid is used in various regimens for non-albicans VVC and recurrent BV. We investigated safety and efficacy of a novel boric acid-based vaginal anti-infective with enhanced antibiofilm activity (TOL-463) in treating BV and VVC., Methods: In this phase 2 randomized, investigator-blinded trial conducted at 2 sexual health clinics, women with BV or VVC were randomly assigned (1:1) to 7 nights of TOL-463 vaginal gel or insert. The primary test of cure (TOC) was clinical cure at day 9-12; safety was assessed at TOC and day 21-30., Results: One hundred six participants (53 with BV, 36 VVC, 17 both) were enrolled; most were African American (69%). Clinical cure rate of BV at TOC was 59% (95% confidence interval [CI], 41%-75%) for TOL-463 insert and 50% (95% CI, 31%-69%) for TOL-463 gel, and for VVC, 92% (95% CI, 67%-99%) for TOL-463 insert and 81% (95% CI, 57%-93%) for TOL-463 gel. Both products were safe and well tolerated with no secondary cases of VVC; vulvovaginal burning was the most common adverse event (9.6%)., Conclusions: TOL-463, especially in vaginal insert form, is effective and safe in treating BV and VVC. Future studies should assess the potential role of TOL-463 as a biofilm disrupter in enhancing likelihood of cure relative to approved therapies, reducing recurrence rates, and combined with traditional antimicrobials., Clinical Trials Registration: NCT02866227., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Sexually transmitted infections (STIs) disproportionately affect men who have sex with men. Although clinical practice guidelines recommend routine STI screening of men who have sex with men who have high-risk behaviors, extragenital STI testing rates have been low in HIV clinics across the nation. The University of Washington STD Prevention Training Center implemented an STI self-testing program at a large HIV primary care clinic in Seattle, WA, to facilitate extragenital STI testing., Methods: We performed a mixed-methods program evaluation to assess health care provider acceptability of the program at 9 months after implementation. Twenty-eight clinicians were invited to complete an online survey. We conducted one-on-one, semistructured interviews with 6 clinicians and a focus group with 7 members of the clinic nursing staff. Survey responses were tallied. Conventional content analysis was performed on survey comments and transcripts from the interviews and focus group., Results: Ninety-one percent of clinicians were either satisfied or very satisfied with the program. Perceived advantages of the program included saving time for clinicians, overcoming patient discomfort, and increasing patient access to testing. Perceived program disadvantages included unclear responsibility of directing patients through the self-testing process and incorrect sample collection and labeling., Conclusions: Despite perceived disadvantages, the self-testing program was acceptable to clinicians and nursing staff, key population for successful program adoption. Implementation of STI self-testing programs in clinic settings could help to increase extragenital STI testing rates by removing provider and patient barriers to testing.

Jeanne M. Marrazzo and colleagues join PLOS Medicine's Collection on the prevention, diagnosis, and treatment of STIs with a Perspective on HIV research imperatives in our time of effective viral suppression and pre-exposure prophylaxis.

Although great progress has been made in treating HIV-1 infection globally, incidence remains high in many locales, especially sub-Saharan Africa. Two-thirds of the burden of disease is there, and among those infected, 60% are women. Pre-exposure prophylaxis, the administration of a drug to prevent acquisition of infection, has proven to be a promising prevention modality for HIV-1 when administered as a daily oral regimen of tenofovir disoproxil fumarate/emtricitabine. However, data suggest that oral tenofovir disoproxil fumarate/emtricitabine may not achieve protective concentrations in the cervicovaginal tissue as rapidly as it does in the rectum. Moreover, a relative paucity of the beneficial vaginal bacteria Lactobacillus crispatus, along with a commensurate increase in the vaginal anaerobes that characterize bacterial vaginosis, strongly increases risk of HIV-1 acquisition and may even modify efficacy of topical tenofovir when used as pre-exposure prophylaxis. bacterial vaginosis, a globally prevalent infection that increases women's risk of HIV-1 acquisition, and presents serious other reproductive health risks and management challenges, presumably involves survival of treatment-resistant biofilm communities. Methods to effect sustained improvement in the vaginal microenvironment are urgently needed., Competing Interests: Potential Conflicts of Interest: None disclosed.

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD.

Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)-based regimens has been shown to be effective in preventing acquisition of HIV infection, with protective efficacy being dependent on adherence to treatment. Data from the PROUD (Preexposure Option for Reducing HIV in the UK) and IPERGAY (Action to Prevent Risk Exposure By and For Gay Men) studies, the later of which employed event-driven PrEP, showed a high rate of protective efficacy of PrEP with TDF and emtricitabine among men who have sex with men. Data from the ASPIRE (A Study to Prevent Infection With a Ring for Extended Use) study of a dapivirine vaginal ring showed a moderate rate of protective efficacy among women older than 21 years. Ongoing investigations are examining long-acting PrEP modalities and combination PrEP and contraception products. This article summarizes a presentation by Jeanne M. Marrazzo, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Washington, DC, in April 2016.

Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) prevented HIV acquisition among men and women in several trials and is broadly recommended. In the VOICE and FEM-PrEP trials, however, TDF/FTC-based PrEP did not prevent HIV acquisition among women in eastern and southern Africa. Tenofovir was detected in plasma, reflecting exposure and adherence in recent days, in fewer than one-third of participants. Drug concentrations in hair, which represent cumulative exposure and adherence over weeks to months, have never previously been examined among women on PrEP. We compared tenofovir hair concentrations among women assigned to oral TDF/FTC in the VOICE trial to those among men and transgender women enrolled in 2 open-label PrEP studies, the iPrEx open-label extension (OLE) study and the U.S. PrEP Demonstration Project (PrEP Demo). Tenofovir hair concentrations were detectable in 55% of person-visits in VOICE, 75% of person-visits in iPrEx OLE (p = .006), and 98% of person-visits in PrEP Demo (p < .001). Median tenofovir hair concentrations corresponded to an estimated 0.2, 2.9, and 6.0 TDF/FTC doses taken per week in the three studies, respectively. In VOICE, combining tenofovir concentration data from plasma and hair suggested inconsistent, low-level product use. Incorporation of both short- and long-term adherence measures may allow for an improved understanding of patterns of drug-taking among women during global PrEP roll-out.

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)