Ecology meets reproductive medicine in HIV prevention: the case for geography-informed approaches for bacterial vaginosis in Africa.

Purpose Of Review: Women in Africa bear the burden of the HIV epidemic, which has been associated with the high prevalence of bacterial vaginosis (BV) in the region. However, little progress has been made in finding an effective cure for BV. Drawing on advances in microbiome-directed therapies for gastrointestinal disorders, similar live-biotherapeutic based approaches for BV treatment are being evaluated.

Natural History of High-Risk Human Papillomavirus in Kenyan and South African Women: Implications for Vaccination Campaigns and Cervical Cancer Screening Programs.

Objective: Human papillomavirus (HPV) vaccines and DNA testing roll out in resource-constrained settings. We evaluated the natural history of HPV infections in African women to contribute to normative guidance.

Methods: Women aged 16 to 35 years were enrolled from 3 sites in South Africa and Kenya and followed quarterly for 18 months.

Systems analysis reveals differential expression of endocervical genes in African women randomized to DMPA-IM, LNG implant or cu-IUD.

Although effective contraceptives are crucial for preventing unintended pregnancies, evidence suggests that their use may perturb the female genital tract (FGT). A comparative analysis of the effects of the most common contraceptives on the FGT have not been evaluated in a randomized clinical trial setting. Here, we evaluated the effect of three long-acting contraceptive methods: depot medroxyprogesterone acetate(DMPA-IM), levonorgestrel(LNG) implant, and a copper intrauterine device (Cu-IUD), on the endocervical host transcriptome in 188 women from the Evidence for Contraceptive Options and HIV Outcomes Trial (ECHO) trial.

"Words are too small": exploring artmaking as a tool to facilitate dialogues with young South African women about their sexual and reproductive health experiences.

Background: Adolescents and young women are at high risk for sexually transmitted infections (STIs) and unintended pregnancies. However, conversations about sexual and reproductive health (S&RH) are difficult and stigmatised. Visual art-based approaches have been a useful adjunct to language-dependent interviews, encouraging embodied memory recall.

Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents.

The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15-19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex).

Cost-effectiveness analysis of different screening and diagnostic strategies for sexually transmitted infections and bacterial vaginosis in women attending primary health care facilities in Cape Town.

Background: Genital inflammation associated with sexually transmitted infections (STIs) and bacterial vaginosis (BV) is considered a key driver in the HIV epidemic. A new rapid point-of-care test (POC) that detects genital inflammation in women-Genital InFlammation Test (GIFT)-was recently developed by researchers at the University of Cape Town. The objective of this study was to establish the cost-effectiveness of this novel intervention relative to other relevant screening and diagnostic strategies for the management of STIs and BV in women seeking care in the public health sector in South Africa.

Shifting the power: scale-up of access to point-of-care and self-testing for sexually transmitted infections in low-income and middle-income settings.

Purpose Of Review: Point-of-care (POC) testing for sexually transmitted infections (STIs) can provide complementary coverage to existing HIV testing services in LMICs. This review summarizes current and emerging technologies for detecting STIs in LMICs, with an emphasis on women, discharge-causing infections (chlamydia, gonorrhoea, trichomoniasis, and syphilis), true POC, self-testing, ethics, and economic considerations related to equitable access.

Recent Findings: The WHO have recently adapted guidelines for treatment of STIs in women that advise the use of true-POC or near-POC tests to improve case finding.

Copper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial.

Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains a lack of rigorous data regarding the effects of contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into a substudy of the ECHO Trial (NCT02550067), we evaluate the effect of injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), and a copper intrauterine device (Cu-IUD) on the vaginal environment after one and six consecutive months of use, using 16S rRNA gene sequencing and multiplex cytokine assays.

A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome.

There is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Here, in this pilot study, we show that asymptomatic urethral infection with (CT) significantly impacts the foreskin proteome composition.

Systems Analysis Reveals Contraceptive-Induced Alteration of Cervicovaginal Gene Expression in a Randomized Trial.

Hormonal contraceptives (HCs) are vital in managing the reproductive health of women. However, HC usage has been linked to perturbations in cervicovaginal immunity and increased risk of sexually transmitted infections. Here, we evaluated the impact of three HCs on the cervicovaginal environment using high-throughput transcriptomics.

Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression.

Background: Women with a cervicovaginal microbiota dominated by Lactobacillus spp. are at reduced risk of acquiring sexually transmitted infections including HIV, but the biological mechanisms involved remain poorly defined. Here, we performed metaproteomics on vaginal swab samples from young South African women (n = 113) and transcriptomics analysis of cervicovaginal epithelial cell cultures to examine the ability of lactic acid, a metabolite produced by cervicovaginal lactobacilli, to modulate genital epithelial barrier function.

Initiating Intramuscular Depot Medroxyprogesterone Acetate Increases Frequencies of Th17-like Human Immunodeficiency Virus Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial.

Background: Cervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells.

Persistent, Asymptomatic Colonization with is Associated with Elevated Frequencies of Highly Activated Cervical Th17-Like Cells and Related Cytokines in the Reproductive Tract of South African Adolescents.

Cervicovaginal inflammation, nonoptimal microbiota, T-cell activation, and hormonal contraceptives may increase HIV risk, yet associations between these factors and subclinical colonization or hyphae are unknown. We collected cervicovaginal samples from 94 South African adolescents, aged 15 to 19 years, who were randomized to injectable norethisterone enanthate (Net-En), an etonorgesterol/ethinyl estradiol vaginal ring (NuvaRing), or oral contraceptives in the UChoose trial (NCT02404038) at baseline and 16 weeks post-randomization. We assessed cervicovaginal samples for subclinical colonization (by quantitative PCR [qPCR]), hyphae (by Gram stain), microbiota composition (by 16S rRNA gene sequencing), cytokine concentrations (by Luminex), and cervical T-cell phenotypes and activation (by multiparameter flow cytometry).

The Effect of Contraception on Genital Cytokines in Women Randomized to Copper Intrauterine Device, Depot Medroxyprogesterone Acetate, or Levonorgestrel Implant.

Background: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls).

In Silico Characterisation of Putative Prophages in Used in Probiotics for Vaginal Health.

While live biotherapeutics offer a promising approach to optimizing vaginal microbiota, the presence of functional prophages within introduced strains could impact their safety and efficacy. We evaluated the presence of prophages in 895 publicly available genomes using Phaster, Phigaro, Phispy, Prophet and Virsorter. Prophages were identified according to stringent (detected by ≥4 methods) or lenient criteria (detected by ≥2 methods), both with >80% reciprocal sequence overlap.

Genital Immune Cell Activation and Tenofovir Gel Efficacy: A Case-Control Study.

Genital inflammation (GI) undermines topical human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4 + T-cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficacy of antiretroviral-based PrEP in women with GI.

Higher mucosal antibody concentrations in women with genital tract inflammation.

Inflammatory cytokines augment humoral responses by stimulating antibody production and inducing class-switching. In women, genital inflammation (GI) significantly modifies HIV risk. However, the impact of GI on mucosal antibodies remains undefined.

Rapid Point-of-Care Testing for Genital Tract Inflammatory Cytokine Biomarkers to Diagnose Asymptomatic Sexually Transmitted Infections and Bacterial Vaginosis in Women: Cost Estimation and Budget Impact Analysis.

Background: Screening for genital inflammation can reveal asymptomatic cases of sexually transmitted infections (STIs) and bacterial vaginosis (BV), useful in settings where only syndromic management is available. This study aimed to estimate the incremental cost of screening using a new cytokine biomarker rapid test and determine the budget impact of providing this service in primary health facilities in South Africa.

Methods: Costs of adding genital inflammation screening to existing family planning services were estimated for women (15-49 years) attending 3 different family planning clinics in US $2016.

Temporal Changes in Vaginal Microbiota and Genital Tract Cytokines Among South African Women Treated for Bacterial Vaginosis.

The standard treatment for bacterial vaginosis (BV) with oral metronidazole is often ineffective, and recurrence rates are high among African women. BV-associated anaerobes are closely associated with genital inflammation and HIV risk, which underscores the importance of understanding the interplay between vaginal microbiota and genital inflammation in response to treatment. In this cohort study, we therefore the effects of metronidazole treatment on the vaginal microbiota and genital cytokines among symptomatic South African women with BV [defined as Nugent score (NS) ≥4] using 16S rRNA gene sequencing and multiplex bead arrays.

Transient association between semen exposure and biomarkers of genital inflammation in South African women at risk of HIV infection.

Introduction: Semen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen-induced alterations are likely short-lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations.

Methods: We assessed stored genital specimens from 152 HIV-negative KwaZulu-Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014.