Articles

Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study

Women may be more susceptible to infections in the luteal phase, supposedly as a consequence of the hormone progesterone and its immunosuppressive action. While immunosuppression may be important for successful oocyte implantation and pregnancy, it makes women more vulnerable to pathogens. According to theory, to compensate for reduced immunocompetence, women in the luteal phase exhibit proactive behavioral responses, such as disgust and avoidance of disease-associated stimuli, to minimize contagion risk. However, previous studies yielded inconsistent results, and did not account for accompanying proactive immune responses, like the increase of secretory immunoglobin A (sIgA). Here, we assessed the proactive immune response and feelings of disgust associated with disease cues in the comparison of 61 woman with a natural menstrual cycle (31 in the follicular and 30 in the luteal phase) and 20 women taking hormonal contraception (HC). Women rated disease vulnerability and disgust propensity, watched a video displaying people with respiratory symptoms, which was evaluated for its disgust-evoking potential and contagiousness, and provided saliva samples for hormone and sIgA analysis. Women with HC reported a heightened vulnerability to disease compared to naturally cycling women, whereas both the feeling of disgust and the sIgA increase elicited by the disease video were similar across groups, regardless of progesterone. We found a u-shaped relationship between progesterone and baseline sIgA in naturally cycling women, with its nadir during ovulation. Overall, our data do not support a compensatory relationship between the proposed progesterone-induced immunosuppression and heightened disgust or a proactive sIgA response.

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. Cu-IUD usage showed the most extensive transcriptomic changes, and was associated with inflammatory and anti-viral host responses. DMPA-IM usage was enriched for pathways associated with T cell responses. LNG implant had the mildest effect on endocervical gene expression, and was associated with growth factor signaling. These data provide a mechanistic basis for the diverse influence that varying contraceptives have on the FGT.

Recent estimates suggest that one in two sexually active individuals will acquire a sexually transmitted infection by age 25, an alarming statistic that amounts to over 1 million new infections per day worldwide. Vaccination against STIs is highly desirable for alleviating this global burden of disease. Vaginal immunization is a promising strategy to combat transmission via the vaginal mucosa. The vagina is typically considered a poor inductive site for common correlates of adaptive immunity. However, emerging evidence suggests that immune tolerance may be overcome by precisely engineered vaccination schemes that orchestrate cell-mediated immunity and establish tissue resident memory immune cells. In this review, we will discuss the unique immunological milieu of the vaginal mucosa and our current understanding of correlates of pathogenesis and protection for several common STIs. We then present a summary of recent vaginal vaccine studies and explore the role that mucosal adjuvants and delivery systems play in enhancing protection according to requisite features of immunity. Finally, we offer perspectives on the challenges and future directions of vaginal vaccine delivery, discussing remaining physiological barriers and innovative vaccine formulations that may overcome them.

Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with a sizable disease burden that is highest in sub-Saharan Africa. This study aimed to characterize HSV-2 epidemiology in this region.

Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings up to August 23, 2020. Meta-analyses and meta-regressions were conducted.

From 218 relevant publications, 451 overall outcome measures and 869 stratified measures were extracted. Pooled incidence rates ranged between 2.4–19.4 per 100 person-years across populations. Pooled seroprevalence was lowest at 37.3% (95% confidence interval (CI): 34.9–39.7%) in general populations and high in female sex workers and HIV-positive individuals at 62.5% (95% CI: 54.8–70.0%) and 71.3% (95% CI: 66.5–75.9%), respectively. In general populations, pooled seroprevalence increased steadily with age. Compared to women, men had a lower seroprevalence with an adjusted risk ratio (ARR) of 0.61 (95% CI: 0.56–0.67). Seroprevalence has decreased in recent decades with an ARR of 0.98 (95% CI: 0.97–0.99) per year. Seroprevalence was highest in Eastern and Southern Africa. Pooled HSV-2 proportion in genital ulcer disease was 50.7% (95% CI: 44.7–56.8%) and in genital herpes it was 97.3% (95% CI: 84.4–100%).

Seroprevalence is declining by 2% per year, but a third of the population is infected. Age and geography play profound roles in HSV-2 epidemiology. Temporal declines and geographic distribution of HSV-2 seroprevalence mirror that of HIV prevalence, suggesting sexual risk behavior has been declining for three decades. HSV-2 is the etiological cause of half of genital ulcer disease and nearly all genital herpes cases with limited role for HSV-1.

This work was supported by pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar and by the Qatar National Research Fund [NPRP 9–040–3–008].