CROI 2024: Global Epidemiology and Prevention of HIV and Other Sexually Transmitted Diseases.

At the 2024 Conference on Retroviruses and Opportunistic Infections (CROI), investigators presented updates on the global HIV epidemic, focusing on ongoing disparities by race/ethnicity in the US, the ongoing concentration of new infections among men who have sex with men (MSM) and transgender women in the Americas, and a shift to a greater total number of infections now in low versus high prevalence countries globally. HIV testing, the gateway to prevention and to treatment, has not fully rebounded from the substantial declines seen during the early COVID-19 pandemic in some settings, although innovative strategies including home testing and opt-out testing in clinical settings appear to be reaching populations in need of testing. Several investigators reported on the efficacy and effectiveness of doxycycline used as postexposure prophylaxis (doxy-PEP) to prevent bacterial sexual transmitted infections in MSM and transgender women in clinical trials and clinic settings; citywide rates of chlamydia and syphilis have decreased in San Francisco after the rollout of the first doxy-PEP guidelines in the US. Lack of doxy-PEP efficacy in cisgender women in Kenya appears due to low adherence in that trial. Rollout and persistence on oral HIV preexposure prophylaxis (PrEP) are associated with reduced seroincidence on a population and individual level. The rollout of long-acting injectable cabotegravir (CAB-LA) PrEP is proceeding slowly in the US. New, longer-acting oral and injectable agents are in development, with preclinical and early clinical trial data presented at CROI. Oral PrEP uptake among populations in sub-Saharan Africa remains low in most settings, suggesting the need for more options and more support; point-of-care tenofovir testing appear acceptable in various populations and may improve adherence and identify PrEP users needing more support. Choice of PrEP or PEP including CAB-LA combined with clinical support substantially increased biomedical prevention coverage in East Africa. Novel approaches to PrEP rollout, including delivery using mobile services and in nonclinical settings appear to show promise. HIV PEP continues to be underutilized.

Adapting mHealth Interventions (PrEPmate and DOT Diary) to Support PrEP Retention in Care and Adherence Among English and Spanish-Speaking Men Who Have Sex With Men and Transgender Women in the United States: Formative Work and Pilot Randomized Trial.

BACKGROUND: A growing number of mobile health (mHealth) technologies are being developed to support HIV preexposure prophylaxis (PrEP) adherence and persistence; however, most tools have focused on men who have sex with men (MSM), and few are available in Spanish. To maximize the potential impact of these tools in reducing gender and racial/ethnic disparities and promoting health equity, mHealth tools tailored to Spanish-speaking people and transgender women are critically needed. OBJECTIVE: The aim of this study is to adapt and tailor 2 mHealth technologies, PrEPmate and DOT Diary, to support daily PrEP adherence and persistence among Spanish-speaking MSM and English- and Spanish-speaking transgender women and to evaluate the feasibility and acceptability of these tools. METHODS: PrEPmate, an interactive, bidirectional, text messaging intervention that promotes personalized communication between PrEP users and providers, and DOT Diary, a mobile app that promotes self-management of PrEP use and sexual health through an integrated electronic pill-taking and sexual activity diary, were previously developed for English-speaking MSM. We conducted 3 focus groups with 15 English- and Spanish-speaking transgender women and MSM in San Francisco and Miami to culturally tailor these tools for these priority populations. We then conducted a 1-month technical pilot among 21 participants to assess the usability and acceptability of the adapted interventions and optimize the functionality of these tools. RESULTS: Participants in focus groups liked the "human touch" of text messages in PrEPmate and thought it would be helpful for scheduling appointments and asking questions. They liked the daily reminder messages, especially the fun facts, gender affirmations, and transgender history topics. Participants recommended changes to tailor the language and messages for Spanish-speaking and transgender populations. For DOT Diary, participants liked the adherence tracking and protection level feedback and thought the calendar functions were easy to use. Based on participant recommendations, we tailored language within the app for Spanish-speaking MSM and transgender women, simplified the sexual diary, and added motivational badges. In the technical pilot of the refined tools, mean System Usability Scale scores were 81.2/100 for PrEPmate and 76.4/100 for DOT Diary (P=.48), falling in the "good" to "excellent" range, and mean Client Satisfaction Questionnaire scores were 28.6 and 28.3 for PrEPmate and DOT Diary, respectively (maximum possible score=32). Use of both tools was high over the 1-month pilot (average of 10.5 messages received from each participant for PrEPmate; average of 17.6 times accessing the DOT Diary app), indicating good feasibility for both tools. CONCLUSIONS: Using a user-centered design approach, we culturally tailored PrEPmate and DOT Diary to support daily PrEP use among Spanish-speaking MSM and English- and Spanish-speaking transgender women. Our positive findings in a technical pilot support further testing of these mHealth interventions in an upcoming comparative effectiveness trial.

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.

Impact of HLA class I functional divergence on HIV control.

Heterozygosity of Human leukocyte antigen (HLA) class I genes is linked to beneficial outcomes after HIV infection, presumably through greater breadth of HIV epitope presentation and cytotoxic T cell response. Distinct allotype pairs, however, differ in the extent to which they bind shared sets of peptides. We developed a functional divergence metric that measures pairwise complementarity of allotype-associated peptide binding profiles. Greater functional divergence for pairs of HLA-A and/or HLA-B allotypes was associated with slower AIDS progression and independently with enhanced viral load control. The metric predicts immune breadth at the peptide level rather than gene level and redefines HLA heterozygosity as a continuum differentially affecting disease outcome. Functional divergence may affect response to additional infections, vaccination, immunotherapy, and other diseases where HLA heterozygote advantage occurs.

Point-of-care urine tenofovir test predicts future HIV preexposure prophylaxis discontinuation among young users.

BACKGROUND: Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower preexposure prophylaxis (PrEP) adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS). METHODS: YMSM/TGW participants ( n  = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/ml) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days. RESULTS: Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (<4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation [adjusted odds ratio (AOR) 6.1; 95% confidence interval (CI): 1.4-11; P  = 0.005] and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value. CONCLUSIONS: In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability.

Rapid Biphasic Decay of Intact and Defective HIV DNA Reservoir During Acute Treated HIV Disease.

Antiretroviral therapy (ART) is not a cure. Upon ART cessation, virus rapidly rebounds from latently-infected cells ("the HIV reservoir"). The reservoir is largely stabilized at the time of ART initiation and then decays slowly. Here, leveraging >500 longitudinal samples from 67 people with HIV (PWH) treated during acute infection, we developed a novel mathematical model to predict reservoir decay using the intact proviral DNA assay (IPDA) from peripheral CD4+ T cells. Nonlinear generalized additive models adjusted for initial CD4+ T count, pre-ART viral load, and timing of ART initiation demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~0.71 months; week 5-24: t1/2 ~3.9 months) that extended out to 1 year of ART, with similar trends for defective DNA. Predicted reservoir decay were faster for participants individuals with earlier timing of ART initiation, higher initial CD4+ T cell count, and lower pre-ART viral load. These estimates are ~5-fold faster than prior reservoir decay estimates among chronic-treated PWH. Thus, these data add to our limited understanding of host viral control at the earliest stages of HIV reservoir stabilization, potentially informing future HIV cure efforts aimed at diverse, global population of PWH initiating ART at varying stages of disease.

Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa. METHODS: This randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18-35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7-24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov, NCT03060629, and is complete. FINDINGS: Between Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20-25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7-24 after the first vaccination was 3·38 (95% CI 2·54-4·41) in the vaccine group and 3·94 (3·04-5·03) in the placebo group, with an estimated VE(7-24) of 14·10% (95% CI -22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE. INTERPRETATION: The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1. FUNDING: Division of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute.

Over-the-counter human immunodeficiency virus self-test kits: time to explore their use for men who have sex with men in Brazil

Increasing access and frequency of human immunodeficiency virus testing are critical to stemming the epidemic. In Brazil's concentrated epidemic, human immunodeficiency virus prevalence in the men who have sex with men/transgender population far exceeds that in the general population, but testing rates fall below what is needed to ensure early detection and treatment. Over-the-counter human immunodeficiency virus self-testing kits, now available in stores in the U.S., have enormous potential to increase testing access and frequency and to facilitate early detection and treatment. With the advent of human immunodeficiency virus self-testing upon us, it is timely to engage the scientific community, government, and civil society in a dialog around how to best utilize this technology in Brazil. We summarize recent research on over-the-counter testing among men who have sex with men, raise potential questions and challenges to using self-tests, suggest implementation strategies, and outline a research agenda moving forward.

Acceptability of self-conducted home-based HIV testing among men who have sex with men in Brazil: data from an on-line survey / Aceitabilidade da autotestagem domiciliar para o HIV entre homens que fazem sexo com homens no Brasil: dados de uma enquete na Internet / Aceptabilidad del examen de VIH autoadministrado en casa con hombres que practican sexo con hombres en Brasil: datos de una encuesta por internet

The Brazilian HIV/AIDS epidemic is concentrated among men who have sex with men (MSM), however HIV testing rates among MSM are not commensurate with their risk. Strategies to expand early diagnosis may include use of self-conducted home-based testing kits, which are now available for purchase in the US. In April 2011 we conducted a survey with Brazilian MSM using Facebook to assess HIV testing preferences and acceptability of home-based testing. Among 356 previously tested, HIV-negative MSM, 47% reported a preference for home-based testing, 27% preferred clinic-based testing, and 26% had no preference. Less frequent testers and those who had considered testing but failed to test were more likely to prefer home-based testing. Close to 90% reported that they would use self-test kits; 62% and 54% said they would use home-based testing to make choices about unprotected sex with regular and new partners, respectively. Concerns included difficulty to understand the tests (32%) and receiving results alone (23%). Overall, home-based testing may appeal to MSM and result in increased testing frequency. Research on feasibility and utilization of self-tests in practice is needed.

A epidemia de HIV/AIDS no Brasil é concentrada em homens que fazem sexo com homens (HSH), mas suas taxas de testagem são incompatíveis com seus riscos. Estratégias para expandir o diagnóstico precoce entre HSH podem incluir kits de autotestagem em ambiente doméstico (AAD), como os disponíveis para compra nos Estados Unidos. Em abril de 2011, realizamos uma pesquisa com HSH brasileiros recrutados em Facebook para conhecer preferências de testagem e aceitabilidade da AAD. Entre 356 HSH HIV(-) testados previamente, 47% preferiam a AAD, 27% testagem em clínicas e 26% sem preferência. HSH com menos testagem ou que consideraram a testagem sem fazê-la tinham maior probabilidade de preferir a AAD (p < 0,05). Quase 90% usariam a AAD, 62 e 54% para decidir sobre ter sexo desprotegido com parceiros regulares e novos, respectivamente. Dificuldade de entender os testes (32%) e receber os resultados sozinhos (23%) foram preocupações referidas. Testes anti-HIV de AAD podem ser atrativos para HSH e resultar em aumento de testagem. Pesquisas com foco na viabilidade e utilização dos kits AAD na prática são necessárias.

La epidemia de VIH/SIDA en Brasil se concentra en hombres que practican sexo con hombres (HSH), pero los índices de exámenes clínicos para conocer si están infectados son incompatibles con sus riesgos. Las estrategias para expandir el diagnóstico precoz entre HSH pueden incluir kits de autoanálisis para el hogar, como los que están a disposición del público en Estados Unidos. En abril de 2011, realizamos una investigación con HSH brasileños, captados en Facebook, para conocer preferencias de exámenes y la aceptabilidad del autoanálisis en un ambiente doméstico. Entre los 356 HSH VIH(-) analizados previamente, un 47% preferían un autoanálisis en un ambiente doméstico, un 27% pruebas en clínicas y un 26% no tenían preferencias. HSH que menos exámenes se realizaron o quienes los consideraron, pero no se los hicieron, tenían mayor probabilidad de preferir el autoanálisis en un ambiente doméstico. Casi un 90% usarían autoanálisis en su hogar, un 62% y 54% con el fin de decidir sobre tener sexo sin protección con parejas regulares y nuevas, respectivamente. La dificultad de entender los análisis (32%) y recibir los resultados a solas (23%) fueron las preocupaciones a las que se refirieron. Los análisis anti-VIH de autoadministración en el hogar pueden ser atractivos para HSH y resultar en un aumento de exámenes. Las investigaciones centradas en la viabilidad y utilización de los test de autoanálisis en la práctica son necesarias.