Impact of Dapivirine and Placebo Vaginal Rings on the Microbiota of Adolescent, Lactating, and Postmenopausal Females

Background A 25 mg dapivirine vaginal ring has been demonstrated to reduce risk of HIV acquisition in nonpregnant adult women. In this secondary analysis of studies conducted in US adolescent, lactating, and postmenopausal females, vaginal microbiota was assessed prior to and after ring use, and between dapivirine and placebo ring users. Methods Vaginal fluid swabs were collected before and after product use for the evaluation of microbiota using Nugent’s criteria, quantitative culture, and qPCR. Results Vaginal ring use did not impact bacterial vaginosis prevalence among the three populations and was associated with minimal shifts in microbiota. Adolescents in both arms demonstrated an increased prevalence of Lactobacillus crispatus and a decrease in quantity of Megasphaera lornae. Postmenopausal active and placebo ring users demonstrated an increased prevalence of lactobacilli and non-albicans yeast while dapivirine ring users demonstrated an increased prevalence of Candida albicans, and increased quantity of Group B Streptococcus (GBS) and non-albicans yeasts. Prevotella species were increased in lactating women while P. timonensis increased in prevalence and concentration among adolescent and postmenopausal women and P. bivia increased in prevalence among adolescent dapivirine ring users. Conclusions Dapivirine vaginal ring use was associated with minimal changes in the vaginal microbiota that are likely not clinically significant.

Beyond bacterial vaginosis: vaginal lactobacilli and HIV risk

HIV incidence continues to be unacceptably high in Eastern and Southern Africa, with women disproportionately affected. An increased per-contact risk of HIV acquisition among African, Caribbean, and other Black (ACB) women has been associated with the higher prevalence of bacterial vaginosis (BV) in these communities, wherein the vaginal microbiota is predominated by diverse pro-inflammatory anaerobic bacteria. However, while the vaginal microbiota in BV-free women is typically predominated by one of several different Lactobacillus spp., the degree of HIV protection afforded by a Lactobacillus-predominant vaginal microbiota also varies considerably. Specifically, L. crispatus is associated with an immunoregulatory genital immune environment, exclusion of BV-associated bacteria, and reduced HIV risk. In contrast, less HIV protection or exclusion of BV-associated bacteria and fewer immune benefits have been associated with L. iners—which is unfortunately the most common Lactobacillus species among ACB women. These species-specific clinical differences are underpinned by substantial genomic differences between Lactobacillus species: for instance, the much smaller genome of L. iners lacks the coding sequence for D-lactic acid dehydrogenase and cannot produce the D-lactate isomer that enhances HIV trapping in mucus but encodes for epithelial cell toxins and stress resistance proteins that may enhance bacterial survival in the context of microbiota and environmental fluctuations. While more studies are needed to elucidate whether differences in HIV protection between Lactobacillus species are due to direct genital immune effects or the exclusion of proinflammatory BV-associated bacteria, the current body of work suggests that for BV treatment to succeed as an HIV prevention strategy, it may be necessary to induce a vaginal microbiota that is predominated by specific (non-iners) Lactobacillus species.

Older Adults Vastly Overestimate Both HIV Acquisition Risk and HIV Prevalence in Rural South Africa

Perceptions of HIV acquisition risk and prevalence shape sexual behavior in sub-Saharan Africa (SSA). We used data from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa baseline survey. Data were collected through home-based interviews of 5059 people ≥ 40 years old. We elicited information on perceived risk of HIV acquisition and HIV prevalence among adults ≥ 15 and ≥ 50 years old. We first describe these perceptions in key subgroups and then compared them to actual estimates for this cohort. We then evaluated the relationship between sociodemographic characteristics and accurate perceptions of prevalence in regression models. Finally, we explored differences in behavioral characteristics among those who overestimated risk compared to those who underestimated or accurately estimated risk. Compared to the actual HIV acquisition risk of < 1%, respondents vastly overestimated this risk: 35% (95% CI: 32–37) and 34% (95% CI: 32–36) for men and women, respectively. Respondents overestimated HIV prevalence at 53% (95% CI: 52–53) for those ≥ 15 years old and 48% (95% CI: 48–49) for those ≥ 50 years old. True values were less than half of these estimates. There were few significant associations between demographic characteristics and accuracy. Finally, high overestimators of HIV prevalence tested themselves less for HIV compared to mild overestimators and accurate reporters. More than 30 years into the HIV epidemic, older people in a community with hyperendemic HIV in SSA vastly overestimate both HIV acquisition risk and prevalence. These misperceptions may lead to fatalism and reduced motivation for prevention efforts, possibly explaining the continued high HIV incidence in this community.

Behavioral effects of different contraceptive methods and HIV acquisition: an ancillary study of the ECHO randomized trial

Background The ECHO trial randomised 7829 women to depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD) and the levonorgestrel (LNG) implant (1:1:1) and found no clear difference in HIV incidence between these three groups. We have previously hypothesized that oligo-amenorrhoea induced by DMPA-IM may have a protective effect on HIV acquisition. The aim of this ancillary study was to assess the effects of DMPA-IM, the IUD and the LNG implant on menstrual symptoms and sexual behavior and to correlate these with HIV acquisition. Methods At the Effective Care Research Unit (ECRU) in South Africa, of 615 women already randomised to DMPA-IM, the copper IUD and the LNG implant (1:1:1) 552 agreed to participate. Participants completed a 28-day symptom and behavior diary following their one-month ECHO trial visit and returning it at their 3-month follow-up visit. HIV acquisition data were retrieved from ECHO trial records. Results Of 552 women enrolled on the ancillary study, 390 (70.6%) completed their daily diary; 130, 133, and 127 received DMPA-IM, IUD, and LNG implant, respectively. Thirty-three (5.9%) of these women acquired HIV. Women on the progestin-only contraceptives were more likely to experience amenorrhoea, as expected, and were less likely to have intra-menstrual coitus than IUD users (p < 0.001 for DMPA-IM vs IUD and p = 0.002 for implant vs IUD). Overall coital frequency was highest and condom usage lowest among DMPA-IM users. Intra-menstrual coitus correlated positively, and duration of menstruation correlated negatively, with HIV acquisition, although these effects were not statistically significant (p = 0.09 and p = 0.079, respectively). Conclusions Findings support the hypothesis that oligo-amenorrhoea and the associated reduced intra-menstrual coitus may mitigate the potential for an increased biological risk of HIV acquisition with DMPA-IM but more evidence is needed. Study registration number PACTR201706001651380

Differentiated Prevention And Care To Reduce The Risk of HIV Acquisition And Transmission Among Female Sex Workers In Zimbabwe: Study Protocol For The ‘AMETHIST’ Cluster Randomised Trial

Background: Female sex workers (FSW) in sub-Saharan Africa are disproportionately affected by HIV and are critical to engage in both HIV prevention and care. Here we describe our approach to evaluation of the AMETHIST intervention for FSW, adapted to the African context and set in Zimbabwe where there is a nationally-scaled programme for sex workers (Sisters). We hypothesise this intervention will raise uptake and adherence to prevention and treatment among FSW resulting in a reduction in their risk of HIV acquisition/transmission.Methods: The AMETHIST intervention (Adapted Microplanning to Eliminate Transmission of HIV in Sex Transactions) aims to provide risk differentiated prevention and care to FSW through microplanning and self help groups. Twenty two towns with the Sisters programme were randomised using restricted randomisation to either the Sisters programme or the Sister programme plus AMETHIST. The primary outcome is composite and is defined as the proportion of HIV positive FSW at risk of HIV transmission combined with the proportion of HIV negative FSW at risk of HIV acquisition. The outcome will be assessed after two years of intervention delivery in a respondent-driven sampling survey (total n=4400; n=200 FSW recruited at each site). Primary analysis will use the ‘RDS-2’ method to estimate cluster summaries and will adapt Hayes and Moulton’s ‘2-step’ method to adjust effect estimates for individual-level confounders and further adjust for cluster baseline prevalence. An in-depth process evaluation guided by our project trajectory will be undertaken.Discussion: Innovative pragmatic trials are needed to generate evidence on effectiveness of combination interventions in HIV prevention and treatment in different contexts. We describe the design and analysis of such a study.Trial Registration: The trial was registered at Pan African Clinical Trials Registry (PACTR202007818077777) on 2 July 2020.

Dynamic Perceived HIV Risk and Sexual Behaviors Among Young Women Enrolled in a PrEP Trial in Kenya: A Qualitative Study

Background: In Kenya and elsewhere in sub-Saharan Africa, young women are disproportionately affected by the HIV epidemic compared to young men. The extent to which young women's self-perceptions about risk of HIV acquisition influence their sexual behaviors and use of HIV prevention methods remains unclear. We therefore conducted a qualitative study to explore these issues among young women enrolled in a pre-exposure prophylaxis (PrEP) trial.Methods: From January 2017 to January 2020, we conducted serial semi-structured in-depth interviews 50 purposively selected young women (18–24 years old) who were participating in the MPYA (Monitoring PrEP for Young Adult women) study—a randomized controlled trial in Thika and Kisumu, Kenya, assessing the impact of SMS reminders on PrEP adherence. Interviews were conducted at three time points (~1 week, 3, and 12 months after initiating PrEP). We used an inductive, content analytic approach to identify key themes related to risk perceptions, sexual behavior, and use of HIV prevention tools.Results: Around the time of enrollment, most of the 50 women interviewed reported being at high risk of HIV because of their own sexual behaviors, such as inconsistent condom use, multiple sexual partners, and transactional sex. Additionally, high risk perception was based on the behavior of their partners, such as refusing to use condoms and being unsure of their partner's HIV status. Young women's perceived risk of HIV acquisition was a key motivator for PrEP initiation and continuation. During PrEP use, participants reported feeling protected and at less risk compared to peers who were not taking PrEP. Some reported no longer using condoms because they were confident that PrEP provided enough protection. Over time, many young women reported reducing risky sexual behaviors because of the regular counseling and HIV testing they received as part of their PrEP services. This lowered risk perception was in most cases accompanied by discontinuation of PrEP.Conclusions: HIV risk perception among young women in Kenya was dynamic and influenced their use of PrEP and condoms over time, suggesting an often-deliberate approach to HIV prevention and sexual health.

Defining the PrEP care continuum among recently incarcerated men at high risk for HIV infection (Preprint)

BACKGROUND HIV disproportionately impacts criminal justice (CJ)-involved individuals, including men who experience incarceration. Men make up the vast majority of those experiencing incarceration as well as those newly diagnosed with HIV infection. Pre-exposure prophylaxis (PrEP) is a highly effective biomedical intervention that significantly reduces the risk of HIV acquisition. However, implementation in CJ-systems is limited. Little is known about effective PrEP implementation and use in this unique public health context. OBJECTIVE This article describes a PrEP care continuum for men experiencing incarceration who are at increased risk of HIV acquisition, which can help conceptualize approaches to evaluating PrEP implementation. METHODS Men incarcerated in the Rhode Island Department of Corrections, a correctional system composed of all of the state's sentenced and awaiting trial population, are screened for HIV acquisition risk during the course of routine clinical care. Those identified at high risk for HIV acquisition are referred for evaluation for PrEP initiation and enrollment in this study. Individuals who express interest in initiating PrEP and consent to the study are then followed in a prospective longitudinal cohort. RESULTS The outlined study will enroll 100 men experiencing incarceration at high risk for HIV acquisition prior to release into the community. The goal is to initiate PrEP prior to incarceration and link individuals to PrEP providers in the community, capturing barriers and facilitators to PrEP use during this uniquely vulnerable time period for HIV acquisition. CONCLUSIONS Based on the proposed care continuum and what is known about HIV risk and prevention efforts in the CJ-context, we outline key future research efforts to better understand effective approaches to preventing HIV infection among this vulnerable population. The described approach presents a powerful public health opportunity to help end the HIV epidemic.

Genital Herpes in Human Immunodeficiency Virus Infected Patients

Genital herpes is a recurrent, lifelong sexual transmitted infection caused by HSV, especially type 2. Genital herpes is the most common infection in HIV patient. HSV-2 can increase the risk of HIV acquisition 2 to 3 times. Clinical manifestations of genital herpes can be different between HIV- infected and non-HIV patients. HIV-infected patients have a high risk of developing chronic and severe genital ulcers with atypical manifestation, prolonged healing, and resistant to treatment, depends on CD4 count. Genital herpes can be diagnosed based on history, clinical manifestation, laboratory and histopathologic examination. Management of genital herpes includes education and counseling patients and sexual partners, systemic antiviral, and symptomatic treatment.