Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion.

Objectives: To examine innate immunity predictors of HIV-1 acquisition as biomarkers of HSV-2 risk and biological basis for epidemiologically established HIV-1 predisposition in HSV-2 infected women.

Methods: We analysed longitudinal samples from HIV-1 negative visits of 1019 women before and after HSV-2 acquisition. We measured cervical and serum biomarkers of inflammation and immune activation previously linked to HIV-1 risk.

Systemic DPP4/CD26 is associated with natural HIV-1 control: Implications for COVID-19 susceptibility.

The current intersection of the COVID-19 and HIV-1 pandemics, has raised concerns about the risk for poor COVID-19 outcomes particularly in regions like sub-Saharan Africa, disproportionally affected by HIV. DPP4/CD26 has been suggested to be a potential therapeutic target and a biomarker for risk in COVID-19 patients with high risk co-morbidities. We therefore evaluated soluble DPP4 (sDPP4) levels and activity in plasma of 131 HIV-infected and 20 HIV-uninfected South African individuals.

The Role of Small Extracellular Vesicles in Viral-Protozoan Symbiosis: Lessons From in an Isogenic Host Parasite Model.

The protozoan parasite (TV), exclusively adapted to the human genital tract, is one of the most common sexually transmitted pathogens. Adding to the complexity of the host-pathogen interactions, the parasite harbors TV-specific endosymbiont viruses (, TVV). It was reported that small extracellular vesicles (sEVs) released by TV play a role in host immunity; however, the role of the viral endosymbiosis in this process remained unknown.

Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age.

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data.

The Current Evidence on the Association Between the Urinary Microbiome and Urinary Incontinence in Women.

Urinary incontinence (UI) is a burdensome condition with high prevalence in middle-aged to older women and an unclear etiology. Advances in our understanding of host-microbe interactions in the urogenital tract have stimulated interest in the urinary microbiome. DNA sequencing and enhanced urine culture suggest that similarly to other mucosal sites, the urinary bladder of healthy individuals harbors resident microbial communities that may play distinct roles in bladder function.

Medroxyprogesterone acetate, unlike norethisterone, increases HIV-1 replication in human peripheral blood mononuclear cells and an indicator cell line, via mechanisms involving the glucocorticoid receptor, increased CD4/CD8 ratios and CCR5 levels.

High usage of progestin-only injectable contraceptives, which include the intramuscular injectables depo-medroxyprogesterone acetate (DMPA-IM, Depo-Provera) and norethisterone (NET) enanthate (NET-EN or Nur-Isterate), correlates worldwide with areas of high HIV-1 prevalence. Epidemiological data show a significant association between usage of DMPA-IM and increased HIV-1 acquisition but no such association from limited data for NET-EN. Whether MPA and NET have similar effects on HIV-1 acquisition and pathogenesis, and the relationship between these effects and the dose of MPA, are critical issues for women's health and access to suitable and safe contraceptives.

The injectable-only contraceptive medroxyprogesterone acetate, unlike norethisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor.

Clinical studies suggest that the injectable contraceptive medroxyprogesterone acetate (MPA) increases susceptibility to infections such as HIV-1, unlike the injectable contraceptive norethisterone enanthate (NET-EN). We investigated the differential effects, molecular mechanism of action and steroid receptor involvement in gene expression by MPA as compared to NET and progesterone (P4) in the End1/E6E7 cell line model for the endocervical epithelium, a key point of entry for pathogens in the female genital mucosa. MPA, unlike NET-acetate (NET-A) and P4, increases mRNA expression of the anti-inflammatory GILZ and IκBα genes.

Differential glucocorticoid receptor-mediated effects on immunomodulatory gene expression by progestin contraceptives: implications for HIV-1 pathogenesis.

Whether hormonal contraceptives increase HIV-1 acquisition, transmission and disease progression are critical questions. Clinical research has been hampered by a lack of understanding that different progestins used in contraception exhibit differential off-target effects via steroid receptors other than the progesterone receptor. Of particular, relevance is the relative effects of medroxyprogesterone acetate (MPA) and norethisterone enanthate (NET-EN), widely used as injectable contraceptives in sub-Saharan Africa.