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.

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.

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.

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).

Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial.

Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15-19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods.

Hormonal contraception and risk of STIs and bacterial vaginosis in South African adolescents: secondary analysis of a randomised trial.

Objectives: Young women in sub-Saharan Africa are at high risk of STIs and unintended pregnancies, yet hormonal contraceptive (HC) use may affect STI risk. We compared the influence of three HCs on the incidence and prevalence of STIs and bacterial vaginosis (BV) in South African adolescents.

Methods: One hundred and thirty adolescents between 15 and 19 years were randomised to the injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) (Triphasil or Nordette) or a combined contraceptive vaginal ring (CCVR; NuvaRing) for 16 weeks (clinicaltrials.

Relationship between the Oral and Vaginal Microbiota of South African Adolescents with High Prevalence of Bacterial Vaginosis.

Bacterial vaginosis (BV) and periodontal disease (PD) are characterised as bacterial dysbioses. Both are associated with an increased risk of poor pregnancy outcomes, yet it is unknown whether PD and BV are related. We characterised the oral microbiota of young South African females with a high prevalence of BV and investigated the association between oral communities and vaginal microbiota.

Exploring potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis.

Antibiotics continue to be the standard-of-care for bacterial vaginosis (BV), although recurrence rates are high. Vaginal probiotics may improve durability of BV treatment, although few probiotics for vaginal health contain Lactobacillus spp. that commonly colonize the lower female genital tract.

Inflammatory and antimicrobial properties differ between vaginal Lactobacillus isolates from South African women with non-optimal versus optimal microbiota.

Female genital tract (FGT) inflammation increases HIV infection susceptibility. Non-optimal cervicovaginal microbiota, characterized by depletion of Lactobacillus species and increased bacterial diversity, is associated with increased FGT cytokine production. Lactobacillus species may protect against HIV partly by reducing FGT inflammation.

Impact of Hormonal Contraceptives on Cervical T-helper 17 Phenotype and Function in Adolescents: Results from a Randomized, Crossover Study Comparing Long-acting Injectable Norethisterone Oenanthate (NET-EN), Combined Oral Contraceptive Pills, and Combined Contraceptive Vaginal Rings.

Background: Adolescents in sub-Saharan Africa are at risk for human immunodeficiency virus (HIV) infection and unintended pregnancies. Observational studies suggest that injectable hormonal contraceptives (HCs) increase the HIV risk, although their effects on genital inflammation, particularly HIV-susceptible T-helper 17 (Th17) cells, are unknown. In a randomized crossover study, the effect of injectable norethisterone oenanthate (NET-EN), combined contraceptive vaginal rings (CCVR; NuvaRing), and combined oral contraceptive pills (COCPs) on cervical Th17 cells and cytokines were compared.

Partner HIV Serostatus Impacts Viral Load, Genital HIV Shedding, and Immune Activation in HIV-Infected Individuals.

Studies of seronegative individuals in HIV discordant relationships provide important insights into the effects of HIV exposure on the seronegative partner, but few have examined the impact of partner serostatus on disease progression in seropositive individuals. We investigated the impact of HIV serostatus on clinical and biological factors influencing HIV disease progression in 337 HIV-infected heterosexual individuals in stable long-term HIV-seroconcordant or HIV-serodiscordant relationships. Seroconcordant individuals had significantly higher plasma viral loads (pVLs) than HIV-infected partners in serodiscordant partnerships [4.

Defining characteristics of genital health in South African adolescent girls and young women at high risk for HIV infection.

The genital tract of African women has been shown to differ from what is currently accepted as 'normal', defined by a pH≤4.5 and lactobacilli-dominated microbiota. Adolescent girls and young women (AGYW) from sub-Saharan Africa are at high risk for HIV, and we hypothesized that specific biological factors are likely to be influential.

Antimicrobial and inflammatory properties of South African clinical Lactobacillus isolates and vaginal probiotics.

Bacterial vaginosis (BV) causes genital inflammation and increased HIV acquisition risk. The standard-of-care for BV, antibiotic therapy, is associated with high recurrence rates. Probiotics may improve treatment outcomes, although substantial heterogeneity in efficacy has been observed during clinical trials.

Lower genital tract cytokine profiles in South African women living with HIV: influence of mucosal sampling.

Measurement of cytokines in the lower female genital tract offer insight into risk for HIV infection and reproductive complications. However, few studies have systematically compared mucosal collection methods or whether collection order matters. We compared longitudinal cytokine profiles in matched genital samples collected from women living with HIV using menstrual cup (MC), endocervical swabs (ECS) and swab-enriched cervicovaginal lavage (eCVL).

Endocervical and vaginal microbiota in South African adolescents with asymptomatic Chlamydia trachomatis infection.

Adolescent girls and young women represent a key risk group for sexually transmitted infections (STIs). The vaginal microbiota is thought to play an important role in susceptibility to STIs such as Chlamydia trachomatis. We compared the microbiota of the lateral vaginal wall and endocervix, and assessed associations with C.

Inflammatory cytokine biomarkers of asymptomatic sexually transmitted infections and vaginal dysbiosis: a multicentre validation study.

Objectives: Vaginal dysbiosis and STIs are important drivers of the HIV epidemic and reproductive complications. These conditions remain prevalent, partly because most cases are asymptomatic. We have shown that inflammatory cytokines interleukin (IL)-1α, IL-1β and interferon-γ-induced protein (IP)-10 are biomarkers for detecting asymptomatic STIs and vaginal dysbiosis (bacterial vaginosis (BV) or intermediate microbiota).

High human papillomavirus (HPV) prevalence in South African adolescents and young women encourages expanded HPV vaccination campaigns.

The objectives of the study were to investigate prevalence of cervical human papillomavirus (HPV) genotypes to inform HPV vaccination strategy in South Africa and to study factors associated with HPV prevalence. Sexually active, HIV-negative women, aged 16-22 years recruited from Soweto (n = 143) and Cape Town (n = 148) were tested for cervical HPV and other genital infections. Overall HPV prevalence was 66.

Converging epidemics of sexually transmitted infections and bacterial vaginosis in southern African female adolescents at risk of HIV.

Adolescents in Africa are at high risk for HIV infection, other sexually transmitted infections (STIs) and bacterial vaginosis (BV). Since behavior and burden of STIs/BV may influence HIV risk, behavioral risk factors and prevalence of STIs/BV were compared in HIV-seronegative adolescent females (n = 298; 16-22 years) from two South African communities (Soweto and Cape Town). STIs ( Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus (HSV)-1, HSV-2, Treponema pallidum, and Haemophilus ducreyi) were detected by multiplex polymerase chain reaction, human papillomavirus (HPV) by Roche Linear Array, and BV by Nugent scoring.

Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females.

Young African females are at an increased risk of HIV acquisition, and genital inflammation or the vaginal microbiome may contribute to this risk. We studied these factors in 168 HIV-negative South African adolescent females aged 16 to 22 years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters (subtypes), one of which was strongly associated with genital inflammation.

CCR5 expression, haplotype and immune activation in protection from infection in HIV-exposed uninfected individuals in HIV-serodiscordant relationships.

Several host factors have been implicated in resistance to HIV infection in individuals who remain HIV-seronegative despite exposure. In a cohort of HIV-serodiscordant heterosexual couples, we investigated interactions between systemic inflammation and T-cell activation in resistance to HIV infection. Males and females in stable long-term relationships with either HIV-infected or uninfected partners were recruited, blood T-cell activation (CD38, HLA-DR, CCR5 and Ki67) and plasma cytokine concentrations were evaluated.

Comparison of sampling methods to measure HIV RNA viral load in female genital tract secretions.

Problem: How does menstrual cup (MC) compare to other genital sampling methods for HIV RNA recovery?

Method Of Study: We compared HIV RNA levels between MC, endocervical swab (ECS), and ECS-enriched cervicovaginal lavage (eCVL) specimens in 51 HIV-positive, antiretroviral therapy-naive women at enrollment, 3 and 6 months, with order rotated by visit. Paired comparisons were analyzed with McNemar's exact tests, signed-rank tests, and an extension of Somer's D for pooled analyses across visits.

Results: MC specimens had the highest proportion of quantifiable HIV VL at enrollment and month 3, but more MC specimens (n=12.

Probiotics for vaginal health in South Africa: what is on retailers' shelves?

Background: Probiotics are widely used to improve gastrointestinal (GI) health, but they may also be useful to prevent or treat gynaecological disorders, including bacterial vaginosis (BV) and candidiasis. BV prevalence is high in South Africa and is associated with increased HIV risk and pregnancy complications. We aimed to assess the availability of probiotics for vaginal health in retail stores (pharmacies, supermarkets and health stores) in two major cities in South Africa.

Female genital tract inflammation, HIV co-infection and persistent mucosal Human Papillomavirus (HPV) infections.

Background: Persistent genital infections with high-risk HPV types increase risk of cervical disease and cancer. Since genital inflammation increases HIV acquisition risk and cancer progression, we evaluated whether HPV infection induces cytokine expression in the reproductive tract.

Methods: Genital cytokines concentrations were measured in 93 HIV-infected and 72 uninfected women.

Role of semen in altering the balance between inflammation and tolerance in the female genital tract: does it contribute to HIV risk?

While the main reproduction aim of semen is the transport of spermatozoa to the female genital tract, seminal plasma is a complex fluid that also carries a broad array of immunologically active molecules. Seminal plasma has been shown to contain a diverse array of anti-inflammatory and pro-inflammatory soluble mediators that regulate immune responses within the female reproductive tract than can facilitate fertilization. Since the natural inflammatory response to semen deposition in the female genital tract may result in recruitment of activated HIV target cells into the female genital mucosa, we discuss the constituents of semen that may increase the risk for HIV infection in women.