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Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV-negative women ages 16-25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP [greater than or equal to]700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted. In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population.

Female sex workers (FSW) have increased risk of HIV infection. Antiretroviral treatment (ART) can improve HIV outcomes and prevent HIV transmission. We analyzed antiretroviral (ARV) drug use and HIV drug resistance among HIV-positive FSW in the Dominican Republic and Tanzania. Plasma samples collected at study entry with viral loads >1,000 copies/mL were tested for ARV drugs and HIV drug resistance. ARV drug testing was performed using a qualitative assay that detects 22 ARV drugs in five classes. HIV genotyping was performed using the ViroSeq HIV-1 Genotyping System. Phylogenetic analyses were performed to determine HIV subtype and assess transmission clusters. Among 410 FSW, 144 (35.1%) had viral loads >1,000 copies/mL (DR: n = 50; Tanzania: n = 94). ARV drugs were detected in 36 (25.0%) of 144 samples. HIV genotyping results were obtained for 138 (95.8%) cases. No transmission clusters were observed in either country. HIV drug resistance was detected in 54 (39.1%) of 138 samples (31/35 [88.6%] with drugs detected; 23/103 [22.3%] without drugs detected); 29/138 (21.0%) had multi-class resistance (MCR). None with MCR had integrase strand transfer inhibitor resistance. In eight cases, one or more ARV drug was detected without corresponding resistance mutations; those women were at risk of acquiring additional drug resistance. Using multivariate logistic regression, resistance was associated with ARV drug detection (p<0.001), self-reported ART (full adherence [p = 0.034]; partial adherence [p<0.001]), and duration of HIV infection (p = 0.013). In this cohort, many women were on ART, but were not virally suppressed. High levels of HIV drug resistance, including MCR, were observed. Resistance was associated with detection of ARV drugs, self-report of ART with full or partial adherence, and duration of HIV infection. These findings highlight the need for better HIV care among FSW to improve their health, reduce HIV drug resistance, and decrease risk of transmission to others.

Background Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, “whole-person” strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit (“mobile unit”) with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. Methods HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of “one-stop” integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. Discussion This trial responds to a need for evidence on using a “whole-person” strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. Trial registration ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

Persons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment. HPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment. Fifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm. In HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART.

Preexposure prophylaxis (PrEP) remains one of the most efficacious interventions for preventing HIV, but its effectiveness is often limited by poor persistence. Although regional efforts have primarily focused on young women and men who have sex with men, heterosexual men in East and Southern Africa represent a crucial group to engage and retain in PrEP care-both to improve health outcomes for men and to interrupt HIV transmission chains. Men seeking sexually transmitted infection (STI) services are particularly vulnerable to HIV acquisition, yet only a few interventions have tested strategies for engaging and retaining these men in PrEP services. Systems navigation, which addresses barriers to health care access and enhances comfort in clinical settings, may offer a promising approach to improving persistent PrEP use among heterosexual men. This study will assess the effect of a peer-delivered systems navigator-facilitated HIV prevention package on PrEP persistence at 26 weeks among heterosexual men seeking STI clinical services in Lilongwe, Malawi. It will also evaluate the acceptability of the intervention and barriers to implementation among key stakeholders. Insights will inform the feasibility of a future randomized controlled trial. In this single-site pilot type I effectiveness-implementation hybrid randomized controlled trial, 200 heterosexual men seeking STI services and initiated on PrEP in Lilongwe, Malawi, will be randomized (1:2) to standard-of-care PrEP services or systems navigator-assisted PrEP care (intervention). Participants will be followed every 13 weeks for at least 26 and up to 52 weeks. PrEP use and engagement in care will be assessed through medical record review and intraerythrocytic tenofovir diphosphate measurement, using objective biomedical analyses via dried blood spot. Primary effectiveness and implementation outcomes include 26-week PrEP persistence (adapted to accommodate daily oral, event-driven oral, or injectable PrEP) and acceptability, respectively. Additional implementation outcomes include feasibility and cost. Exploratory objectives characterize preferences for PrEP modalities, perceived and experienced stigma, and the influence of gender norms on PrEP persistence. All clinical services, including the provision of PrEP and PrEP safety monitoring, are being conducted by the Malawi Ministry of Health. HPTN (HIV Prevention Trials Network) 112 was funded in November 2023. Study recruitment began in April 2024 and closed in November 2024. As of February 3, 2025, the study has enrolled 199 participants, with follow-up expected through June 2025. No interim analyses were planned; data analysis for primary end points is expected in the summer of 2025. Improving PrEP use outcomes among heterosexual men in East and Southern Africa is critical to interrupting HIV transmission. This study offers unique insights into a low-resource, potentially scalable intervention, focusing on a group of men at particularly high risk of HIV acquisition-those with recent STIs. The hybrid RCT design addresses clinically relevant effectiveness questions and explores key determinants that will inform future multisite implementation trials. ClinicalTrials.gov NCT06200545; https://clinicaltrials.gov/study/NCT06200545. DERR1-10.2196/72981.

Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

Preexposure prophylaxis is emerging as an important tool to prevent HIV-1 infection. This report describes an altered presentation of acute HIV infection that may occur with use of long-acting cabotegravir PrEP.

Table 2 Blood bank and pharmacology test results Sample number ABO group Antibody titres Lewis inhibition testing (CAB) ng/mL 1* O anti-A 128 anti-B 128 Le(a-b+)   2 O anti-A 128 anti-B 128 Le(a-b+) 2882† 3 O anti-A 128 anti-B 64 Le(a-b+) 2643† The table shows test results from retrospective testing performed at the Johns Hopkins Hospital Transfusion Medicine Laboratory (Blood Bank testing) and at the HPTN Laboratory Center (Pharmacology testing). *The participant received a long-acting cabotegravir (CAB-LA) injection at this visit. †The CAB concentrations are within expected ranges observed approximately 1 month after a single CAB-LA injection.7 8 We next performed autosomal and Y chromosome short tandem repeat (STR) DNA profiling (online supplemental file 3). In this case, HIV status determination was complicated since the participant received CAB-LA, which can make it hard to detect and confirm HIV infection. Since HIV assay reversion can occur in this setting,1 repeat testing may not be sufficient to resolve HIV status. HPTN 083 study procedures dictate that plasma prepared from up to five whole blood tubes should be pooled before doing laboratory-based testing or aliquoting plasma for storage. Because DNA profiling indicated that the contaminating DNA was present at a high level (8%–21%), it is likely that one of the whole blood tubes used to prepare pooled plasma was from an unrelated person who had HIV infection. [...]it is worth noting that the approaches used for investigation in this report are not specific to cases with unexpected HIV test results but could be used to evaluate other types of unexpected laboratory results.

Monitoring progress towards the UNAIDS ‘first 90’ target requires accurate estimates of levels of diagnosis among people living with HIV (PLHIV), which is often estimated using self-report. We conducted a systematic review and meta-analysis quantifying under-reporting of known HIV-positive status using objective knowledge proxies. Databases were searched for studies providing self-reported and biological/clinical markers of prior knowledge of HIV-positive status among PLHIV. Random-effects models were used to derive pooled estimates of levels of under-reporting. Thirty-two estimates from 26 studies were included (41,465 PLHIV). The pooled proportion under-reporting known HIV-positive status was 20% (95% confidence interval 13–26%, I2 = 99%). In sub-group analysis, under-reporting was higher among men who have sex with men (32%, number of estimates [Ne] = 10) compared to the general population (9%, Ne = 10) and among Black (18%, Ne = 5) than non-Black (3%, Ne = 3) individuals. Supplementing self-reported data with biological/clinical proxies may improve the validity of the ‘first 90’ estimates.

The HIV Prevention Trials Network 052 study enrolled serodiscordant couples. Index participants infected with human immunodeficiency virus reported no prior antiretroviral (ARV) treatment at enrollment. ARV drug testing was performed retrospectively using enrollment samples from a subset of index participants. ARV drugs were detected in 45 of 96 participants (46.9%) with an undetectable viral load, 2 of 48 (4.2%) with a low viral load, and 1 of 65 (1.5%) with a high viral load (P < .0001); they were also detected in follow-up samples from participants who were not receiving study-administered treatment. ARV drug testing may be useful in addition to selfreport of ARV drug use in some clinical trial settings.