Navigating Stigma Against At-Risk Sexual and Gender Minority Populations to End the HIV Epidemic in Sub-Saharan Africa.

In the past year, new laws criminalizing same-sex conduct and the promotion of lesbian, gay, bisexual, transgender, and queer (LGBTQ) rights have emerged as barriers to addressing the HIV epidemic in sub-Saharan Africa (SSA). An augmented approach to addressing HIV within the region's disproportionately affected LGBTQ populations, particularly transgender women and gay, bisexual, and other men who have sex with men (MSM), is imperative for achieving the international goal of ending the HIV epidemic by 2030. In this article, we present recommendations to bolster the continuum of HIV care for MSM and transgender women in SSA.

Enhanced Cohort Methods for HIV Research and Epidemiology (ENCORE): Protocol for a Nationwide Hybrid Cohort for Transgender Women in the United States.

BACKGROUND: In the United States, transgender women are disproportionately impacted by HIV and prioritized in the national strategy to end the epidemic. Individual, interpersonal, and structural vulnerabilities underlie HIV acquisition among transgender women and fuel syndemic conditions, yet no nationwide cohort monitors their HIV and other health outcomes. OBJECTIVE: Our objective is to develop a nationwide cohort to estimate HIV incidence, identify risk factors, and investigate syndemic conditions co-occurring with HIV vulnerability or acquisition among US transgender women. The study is informed by the Syndemics Framework and the Social Ecological Model, positing that stigma-related conditions are synergistically driven by shared multilevel vulnerabilities. METHODS: To address logistical and cost challenges while minimizing technology barriers and research distrust, we aim to establish a novel, hybrid community hub-supported digital cohort (N=3000). The digital cohort is the backbone of the study and is enhanced by hubs strategically located across the United States for increased engagement and in-person support. Study participants are English or Spanish speakers, are aged ≥18 years, identify as transgender women or along the transfeminine spectrum, reside in 1 of the 50 states or Puerto Rico, and do not have HIV (laboratory confirmed). Participants are followed for 24 months, with semiannual assessments. These include a questionnaire and laboratory-based HIV testing using self-collected specimens. Using residential zip codes, person-level data will be merged with contextual geolocated data, including population health measures and economic, housing, and other social and structural factors. Analyses will (1) evaluate the contribution of hub support to the digital cohort using descriptive statistics; (2) estimate and characterize syndemic patterns among transgender women using latent class analysis; (3) examine the role of contextual factors in driving syndemics and HIV prevention over time using multilevel regression models; (4) estimate HIV incidence in transgender women and examine the effect of syndemics and contextual factors on HIV incidence using Poisson regression models; and (5) develop dynamic, compartmental models of multilevel combination HIV prevention interventions among transgender women to simulate their impact on HIV incidence through 2030. RESULTS: Enrollment launched on March 15, 2023, with data collection phases occurring in spring and fall. As of February 24, 2024, a total of 3084 individuals were screened, and 996 (32.3%) met the inclusion criteria and enrolled into the cohort: 2.3% (23/996) enrolled at a hub, and 53.6% (534/996) enrolled through a community hub-supported strategy. Recruitment through purely digital methods contributed 61.5% (1895/3084) of those screened and 42.7% (425/996) of those enrolled in the cohort. CONCLUSIONS: Study findings will inform the development of evidence-based interventions to reduce HIV acquisition and syndemic conditions among US transgender women and advance efforts to end the US HIV epidemic. Methodological findings will also have critical implications for the design of future innovative approaches to HIV research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59846.

The Impact of Stigma and Sexual Identity on PrEP Awareness and Use Among At-Risk Men Who Have Sex With Men in Four U.S. Cities (HPTN 078).

Persistent pre-exposure prophylaxis (PrEP) use reduces the risk of HIV infection, yet uptake lags among those with the greatest need. Sexual identity stigma may be a significant barrier to PrEP awareness and use among high-risk communities. The primary aim of this study was to determine whether sexual identity was related to PrEP awareness and use. This multi-site HIV Prevention Trials Network (HPTN) study (HPTN 078) focuses on men who have sex with men (MSM) (n=335) who were HIV-negative at screening. The majority of participants were non-white (62.1%), younger than 35 (57.9%), single (79.1%), and aware of PrEP, yet had never taken PrEP (52.5%). Participants completed questionnaires including sexual history and identity; lesbian, gay, bisexual, transgender, queer (LGBTQ) community engagement; PrEP awareness and use; and several measures of sexual identity stigma including family and friend stigma, general societal stigma, and anticipated healthcare stigma. Univariate and multinomial logistic regression models helped to determine factors associated with PrEP awareness and use. There were stark disparities in PrEP awareness comparing Black and White participants; 50% of Black participants reported being PrEP unaware vs 11.8% of White participants. In this sample, gay sexual identity (compared to bisexual identity) was associated with increased PrEP awareness (AOR 6.66) and use (AOR 16.9). Additionally, 29% of the association between sexual orientation and PrEP use was mediated through internalized stigma. Given low PrEP uptake among MSM, interventions that address sexual identity stigma may motivate greater PrEP uptake.

Perceived Feasibility and Acceptability of HIV Prevention Research With Daily Oral PrEP Among Young Transgender Women (YTGW) Who Sell or Trade Sex in Bangkok and Pattaya, Thailand.

Young transgender women (YTGW) who sell or trade sex have among the highest HIV incidence rates in Thailand. Using qualitative methods, we assessed perceived acceptability, feasibility, and optimal design of a combination HIV prevention intervention including PrEP for YTGW. Key informant interviews were conducted during July 2016-July 2018 with 21 YTGW, aged 18-26 years, who sold sex and resided in Bangkok or Pattaya, Thailand. Grounded theory and content analysis were used for data analysis. Most YTGW interviewed reported high interest in HIV prevention research and believed participation in it supported sexual health. However, participants perceived HIV studies as complicated and time-consuming. Regarding PrEP, participants suggested more PrEP options beyond daily oral PrEP and expressed concerns related to perceived side effects of PrEP, including interaction with gender-affirming hormone therapy. Improving PrEP knowledge, being able to self-assess HIV risk, and reducing HIV/PrEP stigma could increase interest in research and PrEP uptake among YTGW.

Is HIV epidemic control by 2030 realistic?

Rates of new HIV acquisition remain unacceptably high in most populations in low-income, middle-income, and high-income settings despite advances in treatment and prevention strategies. Although biomedical advances in primary prevention of new infections exist, systematic scale-up of these interventions has not occurred at the pace required to end AIDS by 2030. Low population coverage, adherence to oral pre-exposure prophylaxis in settings with high rates of HIV acquisition, and the fact that a significant proportion of new HIV infections occurs in populations not identified as high risk and are hence not targeted for prevention approaches impedes current prevention strategies. Although long-acting injectables and monoclonal antibodies are promising approaches to help reduce incidence, high cost and the need for high coverage rates mean that a vaccine or vaccine-like intervention still remains the most likely scenario to produce a population-level impact on HIV incidence, especially in countries with generalised epidemics. Current global efforts are not sufficient to meet 2030 HIV epidemic goals; acknowledgment of this issue is required to ensure persistent advocacy for population-based control of the ongoing HIV pandemic.

A Multicomponent Intervention (POSSIBLE) to Improve Perceived Risk for HIV Among Black Sexual Minority Men: Feasibility and Preliminary Effectiveness Pilot Study.

BACKGROUND: Increased pre-exposure prophylaxis (PrEP) use is urgently needed to substantially decrease HIV incidence among Black sexual minority men. Low perceived risk for HIV (PRH) is a key unaddressed PrEP barrier for Black sexual minority men. Peers and smartphone apps are popular intervention tools to promote community health behaviors, but few studies have used these together in a multicomponent strategy. Therefore, we designed a multicomponent intervention called POSSIBLE that used an existing smartphone app called PrEPme (Emocha Mobile Health, Inc) and a peer change agent (PCA) to increase PRH as a gateway to PrEP. OBJECTIVE: This paper aims to describe the feasibility and preliminary impact of POSSIBLE on PRH and willingness to accept a PrEP referral among Black sexual minority men. METHODS: POSSIBLE was a theoretically guided, single-group, 2-session pilot study conducted among Black sexual minority men from Baltimore, Maryland between 2019 and 2021 (N=69). POSSIBLE integrated a PCA and the PrEPme app that allows users to self-monitor sexual risk behaviors and chat with the in-app community health worker to obtain PrEP service information. PRH was assessed using the 8-item PRH scale before and after baseline and follow-up study visits. At the end of each study visit, the PCA referred interested individuals to the community health worker to learn more about PrEP service options. RESULTS: The average age of participants was 32.5 (SD 8.1, range 19-62) years. In total, 55 (80%) participants were retained for follow-up at month 1. After baseline sessions, 29 (42%) participants were willing to be referred to PrEP services, 20 (69%) of those confirmed scheduled appointments with PrEP care teams. There were no statistically significant differences in PRH between baseline and follow-up visits (t122=-1.36; P=.17). CONCLUSIONS: We observed no statistically significant improvement in PRH between baseline and month 1. However, given the high retention rate and acceptability, POSSIBLE may be feasible to implement. Future research should test a statistically powered peer-based approach on PrEP initiation among Black sexual minority men. TRIAL REGISTRATION: ClinicalTrials.gov NCT04533386; https://clinicaltrials.gov/study/NCT04533386.

Performance of the Applied Biosystems HIV-1 Genotyping Kit with Integrase.

HIV genotyping is used to assess HIV susceptibility to antiretroviral drugs. The Applied Biosystems HIV-1 Genotyping Kit with Integrase (AB kit, Thermo Fisher Scientific) detects resistance-associated mutations (RAMs) in HIV protease (PR), reverse transcriptase (RT), and integrase (IN). We compared results from the AB kit with results obtained previously with the ViroSeq HIV-1 Genotyping System. DNA amplicons from the AB kit were also analyzed using next-generation sequencing (NGS). HIV RNA was extracted using the MagNA Pure 24 instrument (Roche Diagnostics; 96 plasma samples, HIV subtype B, viral load range: 530-737,741 copies/mL). FASTA files were generated from AB kit data using Exatype (Hyrax Biosciences). DNA amplicons from the AB kit were also analyzed by NGS using the Nextera XT kit (Illumina). Drug resistance was predicted using the Stanford HIV Drug Resistance Database. The mean genetic distance for sequences from ViroSeq and the AB kit was 0.02% for PR/RT and 0.04% for IN; 103 major RAMs were detected by both methods. Four additional major RAMs were detected by the AB kit only. These four major RAMs were also detected by NGS (detected in 18.1%-38.2% of NGS reads). NGS detected 27 major RAMs that were not detected with either of the Sanger sequencing-based kits. All major RAMs detected with ViroSeq were detected with the AB kit; additional RAMs were detected with the AB kit only. DNA amplicons from the AB kit can be used for NGS for more sensitive detection of RAMs.

A decade of PrEP: the evolution of HIV pre-exposure prophylaxis content and sentiments in South African print news media, 2012-2021.

After nearly a decade of HIV pre-exposure prophylaxis (PrEP) rollout in sub-Saharan Africa, there has been limited study of PrEP messaging in news media. We selected twenty South African newspapers with the highest circulation volumes to retrieve articles published in 2012-2021 mentioning PrEP (N = 249). Using inductive content analysis, we developed a structured codebook to characterise PrEP-related content and sentiments, as well as their evolution over time, in the South African press. Many articles espoused favourable attitudes towards PrEP (52%), but a sizeable fraction espoused unfavourable attitudes (11%). Relative to PrEP-favourable articles, PrEP-unfavourable articles were significantly more likely to emphasise the drawbacks/consequences of PrEP use, including adherence/persistence requirements (52% vs. 24%, p = .007), cost (48% vs. 11%, p < .001), and risk compensation (52% vs. 5%, p < .001). Nevertheless, the presence of these drawbacks/consequences in print media largely declined over time. Key populations (e.g. adolescents, female sex workers) were frequently mentioned potential PrEP candidates. Despite message variations over time, prevention effectiveness and adherence/persistence requirements were the most widely cited PrEP benefits and drawbacks, respectively. Study findings demonstrate the dynamic nature of PrEP coverage in the South African press, likely in response to PrEP scale-up and real-world PrEP implementation during the study period.

Food Insecurity Is High in a Multi-Site Cohort of Transgender Women Vulnerable to or Living with HIV in the Eastern and Southern United States: Baseline Findings from the LITE Cohort.

The prevalence and correlates of food insecurity-the unavailability of food and limited access to it-have not been adequately considered among transgender women (TW), particularly alongside other health-related conditions burdening this population, such as HIV infection. This study examined the prevalence and correlates of food insecurity among TW. Between 2018 and 2020, 1590 TW in the Eastern and Southern U.S. completed a multi-site baseline assessment (socio-behavioral survey and HIV testing). Descriptive statistics were calculated and multivariable Poisson models with robust error variance were used to estimate prevalence ratios and 95% confidence intervals for correlates of food insecurity (dichotomized as sometimes-to-always vs. seldom-to-never running out of food). Eighteen percent of TW were living with HIV and nearly half of participants (44%) reported food insecurity. Correlates of food insecurity included being Black, multiracial, or another race/ethnicity; having < college education, low income, unstable housing, and high anticipated discrimination; and a history of sex work and sexual violence (all p < 0.05). Food insecurity was highly prevalent among TW. Current programs to provide food support do not adequately meet the needs of TW. HIV pr evention and care programs may benefit from addressing food insecurity.

Challenges in Arranging to Waive Parental Consent in HIV Prevention Studies of Adolescent Men Who have Sex with Men: The Case of HPTN 078.

Including adolescent men who have sex with men (AMSM) in HIV prevention and treatment studies without parental permission is vital, but has often faced barriers. We examine the case of recent Institutional Review Boards (IRB) reviews of an HIV treatment and prevention study that requested waiving parental permission at four United States sites, but received different responses from each institution. IRBs varied in whether and how they weighed parental rights against AMSMs' rights and individual and social benefits, and potential harms (e.g., if a parent disapproves of the adolescents' sexual behavior). One IRB "tabled" the decision to receive advice from the university Office of General Counsel (OGC), despite state laws allowing minors to consent to HIV testing and treatment without parental permission. Another IRB consulted the university's Chief Compliance Officer (CCO), which thought the waiver was inconsistent with state law, which discusses "venereal disease," but not HIV. University attorneys may have competing priorities, however, and thus interpret relevant laws differently. This case raises critical concerns, highlighting needs for advocates for AMSM, researchers, IRBs and others at institutional, governmental, and community levels to educate policymakers, public health departments, IRB chairs, members, and staff, OGCs and CCOs about these issues.

Patterns of Polysubstance Use in Young Black and Latinx Sexual Minority Men and Transgender Women and Its Association with Sexual Partnership Factors: The PUSH Study.

Background: Adult studies have demonstrated that polysubstance use increases HIV acquisition risk through increased sexual behaviors, however, few studies have examined polysubstance in young Black and Latinx sexual minority men (SMM) and transgender women (TW). Methods: We used cross-sectional data from 466 young Black and Latinx SMM and TW living in four high HIV-burden US cities enrolled in the PUSH Study, a status-neutral randomized control trial to increase HIV prevention and treatment adherence. We examined data for patterns of polysubstance use comparing age differences of use and explored associations between substance use and sexual partnership factors - inconsistent condom use, pressure to have condomless anal sex, and older partner, using bivariate and multivariate analyses. Results: Most participants described prior substance use with alcohol and cannabis being most common (76% each) and 23% described other illicit drug use, including stimulants, cocaine, hallucinogens, sedatives, opioids, and inhalants. Polysubstance use was common with nearly half (47%) of participants reporting alcohol and cannabis use, 20% reporting alcohol, cannabis, and one other illicit drug use, and 19% reporting alcohol or cannabis use plus one other illicit drug use. Polysubstance use was associated with greater adjusted odds of pressure to have condomless anal sex, older partner (>5 years older), and inconsistent condom use. Conclusions: Associations of polysubstance use with sexual practices and sexual partnerships that are known predictors of HIV acquisition or transmission among Black and Latinx SMM and TW underscore the need for combination interventions that include substance use treatment alongside antiretroviral-based and partner-based HIV prevention and treatment interventions.Trial Registration: ClinicalTrials.gov Identifier: NCT03194477.

PrEP initiation and discontinuation among transgender women in the United States: a longitudinal, mixed methods cohort study.

INTRODUCTION: Transgender women in the United States experience high HIV incidence and suboptimal Pre-exposure prophylaxis (PrEP) engagement. We sought to estimate PrEP initiation and discontinuation rates and characterize PrEP discontinuation experiences among a prospective cohort of transgender women. METHODS: Using a sequential, explanatory, mixed-methods design, 1312 transgender women at risk for HIV acquisition were enrolled from March 2018 to August 2020 and followed through July 2022 (median follow-up 24 months; interquartile range 15-36). Cox regression models assessed predictors of initiation and discontinuation. In-depth interviews were conducted among 18 participants, including life history calendars to explore key events and experiences surrounding discontinuations. Qualitative and quantitative data were integrated to generate typologies of discontinuation, inform meta-inferences and facilitate the interpretation of findings. RESULTS: 21.8% (n = 286) of participants reported taking PrEP at one or more study visits while under observation. We observed 139 PrEP initiations over 2127 person-years (6.5 initiations/100 person-years, 95% CI: 5.5-7.7). Predictors of initiation included identifying as Black and PrEP indication. The rate of initiation among those who were PrEP-indicated was 9.6 initiations/100 person-years (132/1372 person-years; 95% CI: 8.1-11.4). We observed 138 PrEP discontinuations over 368 person-years (37.5 discontinuations/100 person-years, 95% CI: 31.7-44.3). Predictors of discontinuation included high school education or less and initiating PrEP for the first time while under observation. Four discontinuation typologies emerged: (1) seroconversion following discontinuation; (2) ongoing HIV acquisition risk following discontinuation; (3) reassessment of HIV/STI prevention strategy following discontinuation; and (4) dynamic PrEP use coinciding with changes in HIV acquisition risk. CONCLUSIONS: PrEP initiation rates were low and discontinuation rates were high. Complex motivations to stop using PrEP did not consistently correspond with HIV acquisition risk reduction. Evidence-based interventions to increase PrEP persistence among transgender women with ongoing acquisition risk and provide HIV prevention support for those who discontinue PrEP are necessary to reduce HIV incidence in this population.

HIV and fungal priority pathogens.

The burden of invasive fungal infections associated with opportunistic fungal pathogens is a persistent challenge, particularly among people with advanced HIV disease. In October, 2022, WHO published the Fungal Priority Pathogens List (FPPL)-the first global effort to systematically prioritise fungal pathogens. Of the 19 pathogens in the WHO FPPL, four opportunistic pathogens in particular cause invasive diseases in people living with HIV: Cryptococcus neoformans, Histoplasma spp, Pneumocystis jirovecii, and Talaromyces marneffei. These four fungal pathogens are major causes of illness and death in people with advanced HIV and overwhelmingly affect those in low-income and middle-income countries. Access to diagnostics, improved surveillance, targeted support for innovation, and an enhanced public health focus on these diseases are needed in the effort to reduce HIV-associated deaths.

HIV infection.

The AIDS epidemic has been a global public health issue for more than 40 years and has resulted in ~40 million deaths. AIDS is caused by the retrovirus, HIV-1, which is transmitted via body fluids and secretions. After infection, the virus invades host cells by attaching to CD4 receptors and thereafter one of two major chemokine coreceptors, CCR5 or CXCR4, destroying the host cell, most often a T lymphocyte, as it replicates. If unchecked this can lead to an immune-deficient state and demise over a period of ~2-10 years. The discovery and global roll-out of rapid diagnostics and effective antiretroviral therapy led to a large reduction in mortality and morbidity and to an expanding group of individuals requiring lifelong viral suppressive therapy. Viral suppression eliminates sexual transmission of the virus and greatly improves health outcomes. HIV infection, although still stigmatized, is now a chronic and manageable condition. Ultimate epidemic control will require prevention and treatment to be made available, affordable and accessible for all. Furthermore, the focus should be heavily oriented towards long-term well-being, care for multimorbidity and good quality of life. Intense research efforts continue for therapeutic and/or preventive vaccines, novel immunotherapies and a cure.