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Pregnant and lactating persons in sub-Saharan Africa face a heightened risk of HIV acquisition, due to biological and behavioral factors, combined with limited access to prevention and treatment services. Oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring are promising tools for HIV prevention, and the ring's recent approval in multiple African countries represents a significant advancement in expanding access to HIV prevention. In a nested qualitative study within the MTN-042 trial, we explored the acceptability of study products among pregnant persons in the second and early third trimesters. Interviews were conducted privately, using a semi-structured guide with 77 participants, in participants' preferred language. Topics explored included product acceptability (using the theoretical framework of acceptability), user experience, satisfaction, disclosure, community attitudes, and sexual activity during pregnancy. Interview transcripts were analyzed using Dedoose software. We observed positive attitudes among participants towards the study products, which they found generally user-friendly, despite the added complexities of using them during pregnancy. Participants recognized that consistent and correct use would provide protection for both them and their unborn children. Although initial concerns existed, most of these worries dissipated over time, with study staff support and increased product use experience. These findings emphasize the importance of continued surveillance, support, and education to ensure the successful rollout of new HIV prevention measures during pregnancy., (© 2024. The Author(s).)

Objective: Biological markers of stress have been associated with HIV progression and pathogenesis but not with HIV incidence. We sought to determine if elevated stress-responsive biomarkers would be associated with incident HIV among adolescent girls and young women (AGYW)., Design: We conducted a case-cohort study within the HIV Prevention Trials Network (HPTN) 068 study among 949 AGYW in South Africa. Cases were AGYW who tested HIV-positive during the eight-year follow-up. Unmatched controls were randomly selected from the HIV-negative population at enrollment., Methods: Dried blood spots from cases and controls were tested from enrollment (2011-2012) for C-reactive protein (CRP), herpes simplex virus type-1 (HSV-1) antibody titers, and cytomegalovirus (CMV) antibody titers. Cox proportional hazards models estimated the association between each biomarker and time to incident HIV., Results: Compared to AGYW with the lowest CRP levels, those with medium and high CRP levels had a higher hazard ratio (HR) of incident HIV [HR: 1.45, 95% confidence interval (CI): 0.95, 2.21; HR: 1.50, 95% CI: 0.98, 2.30, respectively], although not statistically significant. The relative hazard of incident HIV was also higher among AGYW who were CMV seropositive vs. seronegative (low antibodies HR: 2.18, 95% CI: 1.2, 3.87; medium HR: 2.25, 95% CI: 1.28, 3.95; high HR: 1.78, 95% CI: 0.99, 3.21). Those with the highest HSV-1 antibody levels experienced an increased hazard of HIV compared to those who were HSV-1 seronegative (HR: 1.58, 95% CI: 1.03, 2.44)., Conclusions: Biological stress may increase AGYW's susceptibility to HIV acquisition through changes in immune function, viral infection, and increased biological vulnerability to disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Mpox disproportionately impacts Black people and young adults, yet the beliefs and knowledge of mpox among groups at elevated risk remain unclear. Therefore, we assessed mpox knowledge among Black young adults to inform public health efforts., Methods: We surveyed a sample (n = 330) of young Black adults (aged 18-29 years) in Alabama, Georgia, and North Carolina using nine true-or-false questions to assess their mpox knowledge., Results: Correct response rates varied (26%-96%). Approximately 26% were unaware of the mpox vaccine, and almost 21% incorrectly thought the chickenpox vaccine conferred protection against mpox. Females demonstrated statistically significantly higher mpox knowledge than males across 33% of indicators., Discussion: There were no statistically significant differences between states, suggesting that a regional approach may be suitable to improve knowledge. Findings underscore the importance of education and public health initiatives to address mpox knowledge gaps, particularly among Black young adults, to improve public health preparedness., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Few validated brief scales are available to measure constructs that may hinder mpox-related prevention and care engagement, such as knowledge and stigma. Both are highly salient barriers to infectious disease care and disease understanding, precursors to evaluating one's risk and need to, for example, accept vaccination. To address this gap, we developed and validated the Mpox Stigma Scale (MSS) and Mpox Knowledge Scale (MKS)., Methods: As part of a full-scale clinical trial, we offered an optional mpox survey to participants who self-identified as African American or Black, were 18-29 years old, and lived in Alabama, Georgia, or North Carolina (2023, N = 330). We calculated psychometric properties through confirmatory factor analyses (CFA) and applied Comparative Fit Index (CFI), Goodness of Fit Index (GFI), and Tucker-Lewis Index (TLI) values equal to or exceeding 0.90 and Root Mean Square Error of Approximation (RMSEA) and Standardized Root Mean Square Residual (SRMR) values less than 0.08 to determine adequate model fit. We computed internal reliability using Cronbach's alpha and calculated Pearson or Spearman correlation coefficients between the MSS and MKS and related variables., Results: For the MSS, CFA results showed that the one-factor model fit the data well (χ 2 (df = 5, N = 330) = 34.962, CFI = 0.97, GFI = 0.99, TLI = 0.94, RMSEA = 0.13, SRMR = 0.03). For the MKS, the one-factor model provided a good fit to the data (χ 2 (df = 6, N = 330) = 8.44, CFI = 0.99, GFI = 0.99, TLI = 0.95, RMSEA = 0.15, SRMR = 0.02). Cronbach's alphas were MSS = 0.91 and MKS = 0.83, suggesting good to excellent reliability. The MSS was correlated with the MKS (r = .55, p < .001), stigmatizing attitudes (r = .24, p < .001), attitudes towards mpox vaccination (r=-.12, p = .030), and worry about contracting mpox (r = .44, p < .001). The MKS was correlated with worry about contracting mpox (r = .30, p < .001) and mpox disclosure (r=-.16, p = .003)., Conclusions: The MSS and MKS are reliable and valid tools for public health practice, treatment and prevention research, and behavioral science. Further validation is warranted across populations and geographic locations., Trial Registration: ClinicalTrials.gov NCT05490329., (© 2024. The Author(s).)

Transactional sex and sexual relationships with older partners increase HIV risk in adolescent girls and young women (AGYW), yet little is known about how these behaviors co-evolve over time. We characterize temporal patterns of transactional sex and age-disparate relationships among AGYW in South Africa. Longitudinal data are from a randomized controlled trial (HPTN 068) of school-aged, HIV-negative, AGYW who attended ≥ 3 study visits. We used group-based trajectory modeling to identify trajectories of transactional sex and age-disparate relationships (partner ≥ 5 years older) in the last year and assessed the interrelationship (conditional probability) between both trajectories. At baseline, median age was 14 years, 14.5% of girls were sexually active, and transactional sex (2.1%) and age-disparate relationships were uncommon (2.7%). We identified two trajectories for transactional sex ("low" [81.9%] and "increasing" [18.1%]) and two for age-disparate relationships ("low" [91.7%] and "increasing" [8.3%]). In a separate joint trajectory analysis, nearly a third (28%) had increasing trajectories for both transactional sex and age-disparate relationships, but most (53%) had a low trajectory of both outcomes. Baseline reporting of early sexual debut, depression, and inequitable gender norms were highest in the increasing transactional sex group. Prior pregnancy, early sexual debut, and IPV were highest among those with increasing age-disparate relationships. AGYW who engage in transactional sex or age-disparate partnerships in early adolescence are more likely to experience sustained engagement in both behaviors as they transition to adulthood, increasing HIV risk. Engaging girls early may maximize effectiveness of behavioral and biomedical HIV prevention efforts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Depression is associated with lower adherence to oral pre-exposure prophylaxis (PrEP) to prevent HIV, but data are not currently available on how depression may affect use of other HIV prevention methods including the dapivirine vaginal ring (DVR). We conducted a mixed methods study using data from the Microbicide Trials Network (MTN) 042/DELIVER (n = 558) and MTN-043/B-PROTECTED (n = 197) studies to describe the prevalence of depressive symptoms and explore how depressive symptoms may have influenced attitudes about use of the monthly DVR and once-daily oral PrEP tablet among pregnant and breastfeeding persons, respectively, in Malawi, South Africa, Uganda, and Zimbabwe. Eleven participants had high Edinburgh Postnatal Depression scores ≥ 10 in MTN-042/DELIVER (2%) and four participants (2%) in MTN-043/B-PROTECTED. In interviews with 9 participants who had high scores (6 DVR, 3 oral PrEP), those with depressive symptoms described overlapping stressors which were magnified by job loss and economic instability during the COVID-19 pandemic, and by experiences of pregnancy/postpartum. These participants experienced a lack of support from partners or family members, and conflict with partners related to trust, and infidelity. While we did not find evidence of a change in product adherence, there was a strong sense of commitment and motivation to use the study products for protection from HIV for participants themselves and their baby. Although lack of social support is usually an obstacle to adherence, in this study, the participants' lives and relationships seemed to have reinforced the need for HIV prevention and motivated women to protect themselves and their babies from HIV., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite improvements in antiretroviral therapy (ART) availability, suboptimal adherence is common among youth with HIV (YWH) and can increase drug resistance and poor clinical outcomes. Our study examined an innovative mobile app-based intervention that used automated directly observed therapy (aDOT) using artificial intelligence, along with conditional economic incentives (CEIs) to improve ART adherence and enhance viral suppression among YWH., Setting: We conducted a pilot study of the aDOT-CEI intervention, informed by the operant framework of Key Principles in Contingency Management Implementation, to improve ART adherence among YWH (18-29) in California and Florida who had an unsuppressed HIV viral load., Methods: We recruited 28 virally unsuppressed YWH from AIDS Healthcare Foundation clinics, who used the aDOT platform for 3 months. Study outcomes included feasibility and acceptability, self-reported ART adherence, and HIV viral load., Results: Participants reported high satisfaction with the app (91%), and 82% said that it helped them take their medication. Comfort with the security and privacy of the app was moderate (55%), and 59% indicated the incentives helped improve daily adherence., Conclusions: Acceptability and feasibility of the aDOT-CEI intervention were high with potential to improve viral suppression, although some a priori metrics were not met. Pilot results suggest refinements which may improve intervention outcomes, including increased incentive amounts, provision of additional information, and reassurance about app privacy and security. Additional research is recommended to test the efficacy of the aDOT-CEI intervention to improve viral suppression in a larger sample., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Cash transfers can reduce adolescent girls and young women's (AGYW) risk of intimate partner violence (IPV). In our own cash transfer intervention (HPTN 068), AGYW who received a cash transfer were less likely to experience IPV than non-recipients, in part because the cash reduced their engagement in sexual partnerships. This mixed-methods study builds on earlier findings to examine whether the protective effects were sustained after the cash ended and when the cash transfer was the most impactful., Methods: HPTN 068 was an experimental HIV prevention intervention trial. AGYW who participated completed 3 annual surveys during the intervention and an additional survey 2.5 years post-intervention. We used log-binomial regression models to assess the durability of the cash transfer on outcomes and included an interaction term in models to examine when effects were largest. We analyzed qualitative interviews conducted after the cash ended to contextualize findings., Results: Post-intervention, the relative risk of physical IPV was lower among AGYW who received it compared to those who did not, but not statistically significant (RR: 0.83, 95% CI: 0.62, 1.10). AGYW who received the cash transfer also had a lower relative risk of ever having had sex and of having any sexual partner in the last 12 months (RR: 0.94, 95% CI: 0.88, 1.01; RR: 0.94; 95% CI: 0.88, 0.99, respectively). The protective effect of the cash transfer on physical IPV was highest in Years 1 and 2 (RR: 0.64; 95% CI: 0.55-0.75 and RR: 0.65; 95% CI: 0.55-0.77, respectively). Qualitative data corroborated the quantitative findings., Conclusion: The cash transfer reduced AGYW's risk of IPV, though effects were attenuated after the cash ended. Provision of cash during adolescence - a period when AGYW are highly susceptible to IPV and HIV - may empower them in their current relationship and yield long term health benefits., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although stigma has been associated with people living with HIV defaulting from care, there is a gap in understanding the specific impact of individual stigma and community-level concern about HIV on defaulting., Methods: This is a secondary analysis of a unique dataset that links health facility-based medical records to a population-representative community survey conducted in 2018 in rural Mpumalanga province, South Africa. We used the parametric g-formula to estimate associations among individual anticipated stigma, low perceived community and local leader concern about HIV, and defaulting from care in the prior year. In addition, we estimated the population-level effects of intervening to reduce stigma and increase concern on defaulting., Results: Among 319 participants on treatment, 42 (13.2%) defaulted from care during the prior year. Anticipated stigma (risk ratio [RR] 1.22, 95% confidence interval [CI]: 0.72, 2.74), low perceived concern about HIV/AIDS from community leadership (RR 1.12, 95% CI 0.76, 3.38), and low shared concerns about HIV/AIDS in the community (RR 1.37; 95% CI 0.79, 3.07) were not significantly associated with default. Hypothetical population intervention effects to remove individual anticipated stigma and low community concerns yielded small reductions in default (~1% reduction)., Conclusions: In this sample, we found limited impact of reducing anticipated stigma and increasing shared concern about HIV on retention in care. Future studies should consider the limitations of this study by examining the influence of other sources of stigma in more detail and assessing how perceptions of stigma and concern impact the full HIV testing and care cascade., Competing Interests: Conflict of Interest Statement: The authors declare that they have no competing interests.

The Microbicide Trials Network 042 study (MTN-042/DELIVER) is a two-arm, randomized, open-label Phase 3b trial that is evaluating the safety, adherence, and acceptability of the monthly ring and daily oral PrEP among HIV-uninfected pregnant people in four African countries. This analysis focuses on acceptability data captured qualitatively from a subset (n = 48) of the 150 people in the first cohort of the trial who were enrolled in late-stage pregnancy at 36 to 38 weeks gestational age and followed until after delivery. Single IDIs were conducted by trained interviewers at each clinic site using a semi-structured guide. Data excerpts of key codes pertaining to acceptability, pregnancy, and maternal health were summarized, reviewed and interpreted by multinational analyst teams. Although the product use period was relatively short, the data suggested several acceptability findings that may directly translate to longer durations of product use in pregnancy. The first was the overarching maternal sentiment that being able to protect both oneself and their baby was highly valued. The second was the importance of counseling support from providers not only because participants used methods that might generate side effects, but because pregnancy itself is a period with its own set of side effects. The third was that, similar to non-pregnant participants in other trials, here study products were generally liked and described as easy to use. Concerns about ring and oral PrEP use could be addressed with provider counseling and support and should form an essential component rollout among pregnant people., (© 2023. The Author(s).)

We assessed if acceptability of the dapivirine vaginal ring for HIV prevention differed among the subgroup of women who reported engaging in transactional sex prior to enrollment in MTN-020/ASPIRE (phase III trial in Malawi, South Africa, Uganda, and Zimbabwe, 2012-2015; n  = 2629). Transactional sex was defined as receipt of money, goods, gifts, drugs, or shelter in exchange for sex in the past year. Dimensions of acceptability included: ease of use and physical sensation in situ, impacts on sex, partner's opinion, and likelihood of future use. We used Poisson regression models with robust standard errors to compare risk of acceptability challenges by baseline history of transactional sex. At product discontinuation, women exchanging sex found the ring comfortable (90%), easy to insert (92%) and nearly all (96%) were likely to use the ring in the future. Women who had exchanged sex were more likely to report feeling the ring during sex (ARR 1.43, 95% CI: 1.09, 1.89; p  = 0.01) and slightly more likely to mind wearing the ring during menses (ARR 1.22, 95% CI: 1.01, 1,46; p  = 0.04) and during sex (ARR 1.22, 95% CI: 1.02, 1.45; p  = 0.03). Messaging and counseling should include enhanced support for use during sex and menses to support optimal use.

Background: Young adults have a disproportionately high rate of HIV infection, high rates of attrition at all stages of the HIV care continuum, and an elevated probability of disease progression and transmission. Tracking and monitoring objective measures of antiretroviral therapy (ART) adherence in real time is critical to bolster the accuracy of research data, support adherence, and improve clinical outcomes. However, adherence monitoring often relies on self-reported and retrospective data or requires additional effort from providers to understand individual adherence patterns. In this study, we will monitor medication-taking using a real-time objective measure of adherence that does not rely on self-report or healthcare providers for measurement., Methods: The Youth Ending the HIV Epidemic (YEHE) study will pilot a novel automated directly observed therapy-conditional economic incentive (aDOT-CEI) intervention to improve ART adherence among youth with HIV (YWH) in California and Florida who have an unsuppressed HIV viral load. The aDOT app uses facial recognition to record adherence each day, and then economic incentives are given based on a participant's confirmed adherence. We will enroll participants in a 3-month pilot study to assess the feasibility and acceptability of the aDOT-CEI intervention using predefined metrics. During and after the trial, a subsample of the pilot participants and staff/providers from participating AIDS Healthcare Foundation (AHF) clinics will participate in individual in-depth interviews to explore intervention and implementation facilitators and barriers., Discussion: YEHE will provide data on the use of an aDOT-CEI intervention to improve adherence among YWH who are not virologically suppressed. The YEHE study will document the feasibility and acceptability and will explore preliminary data to inform a trial to test the efficacy of aDOT-CEI. This intervention has the potential to effectively improve ART adherence and virologic suppression among a key population experiencing health disparities., Trial Registration: The trial registration number is NCT05789875., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Stoner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study examines qualitative acceptability of the dapivirine vaginal ring (DVR) and oral daily pre-exposure prophylaxis (PrEP) among breastfeeding persons participating in Microbicide Trials Network 043/B-PROTECTED, a phase 3B safety and drug detectability study of DVR and oral PrEP in breastfeeding. A subsample of 52 participants were purposively sampled to participate in an in-depth interview (IDI). Breastfeeding participants found both study products to be acceptable, and easy to use. A common motivation for product use was to protect the baby from HIV, although participants' understanding of how the study drug would work to protect their babies was often unclear. While most participants did not report experiencing side effects, fears about side effects were common as both initial worries about how the study products would affect their health and the health of their baby, and increased anxiety that health issues experienced by them, or their baby were from the products., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The COVID-19 pandemic greatly impacted HIV prevention and care globally. The pandemic also had disproportionate impacts on the financial, emotional, and physical wellbeing of women and girls in East and Southern Africa, who were already at increased HIV vulnerability. This study aimed to understand how the COVID-19 pandemic and its response efforts impacted the sexual behavior, HIV prevention interest, general healthcare access, and other HIV risk factors of women and girls in HIV prevention studies., Methods: Using the socio-ecological model (SEM), an explanatory sequential mixed-methods analysis was performed with data from four Microbicide Trial Network (MTN) studies on different populations-adolescent girls and young women (AGYW), pregnant persons, breastfeeding persons, and couples-in Malawi, South Africa, Uganda, and Zimbabwe. Descriptive statistics for outcomes of interest were calculated within each study separately and Chi-squared tests of independence were performed to evaluate associations between study population and outcomes. Excerpts from study qualitative interviews were stratified into code reports which were then summarized into memos with key themes and considerations of the SEM framework to provide context to quantitative findings., Results: Few participants (8/731) had known or suspected COVID-19 infection. Sexual frequency and alcohol use decreased most often among AGYW compared to pregnant or breastfeeding women and couples ( p -value < 0.001). The pandemic had little impact on changes in reported HIV prevention interest or access to HIV prevention study products. Healthcare access was impacted for everyone, with couples most likely to report decreases in access ( p -value < 0.001). From qualitative interviews, economic instability, adverse mental health, and increased violence due to COVID-19 caused increased strain on other factors related to HIV vulnerability., Conclusions: While interest in HIV prevention did not change and a few HIV risks decreased for most women and girls, other vulnerabilities to HIV increased due to the COVID-19 pandemic, highlighting the importance of continued access to HIV prevention for women and girls. More research is needed to better understand the long-term impact of COVID-19 on HIV prevention and vulnerability in community populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Mancuso, Mathebula, Chitukuta, Matambanadzo, Tenza, Reddy, Nobula, Kemigisha and Stoner.)

Introduction: Young adults with HIV (YWH) experience worse clinical outcomes than adults and have high rates of substance use (SU) and mental illness that impact their engagement in care and adherence to antiretroviral therapy (ART). The intervention for Virologic Suppression in Youth (iVY) aims to address treatment engagement/adherence, mental health (MH) and SU in a tailored manner using a differentiated care approach that is youth friendly. Findings will provide information about the impact of iVY on HIV virological suppression, MH and SU among YWH who are disproportionately impacted by HIV and at elevated risk for poor health outcomes., Methods and Analysis: The iVY study will test the effect of a technology-based intervention with differing levels of resource requirements (ie, financial and personnel time) in a randomised clinical trial with an adaptive treatment strategy among 200 YWH (18-29 years old). The primary outcome is HIV virological suppression measured via dried blood spot. This piloted and protocolised intervention combines: (1) brief weekly sessions with a counsellor via a video-chat platform (video-counselling) to discuss MH, SU, HIV care engagement/adherence and other barriers to care; and (2) a mobile health app to address barriers such as ART forgetfulness, and social isolation. iVY has the potential to address important, distinct and changing barriers to HIV care engagement (eg, MH, SU) to increase virological suppression among YWH at elevated risk for poor health outcomes., Ethics and Dissemination: This study and its protocols have been approved by the University of California, San Francisco Institutional Review Board. Study staff will work with a Youth Advisory Panel to disseminate results to YWH, participants and the academic community., Trial Registration Number: NCT05877729., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Current guidance states that asymptomatic screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) prior to admission to an acute-care setting is at the facility's discretion. This study's objective was to estimate the number of undetected cases of SARS-CoV-2 admitted as inpatients under 4 testing approaches and varying assumptions., Design and Setting: Individual-based microsimulation of 104 North Carolina acute-care hospitals., Patients: All simulated inpatient admissions to acute-care hospitals from December 15, 2021, to January 13, 2022 [ie, during the SARS-COV-2 ο (omicron) variant surge]., Interventions: We simulated (1) only testing symptomatic patients, (2) 1-stage antigen testing with no confirmatory polymerase chain reaction (PCR) test, (3) 1-stage antigen testing with a confirmatory PCR for negative results, and (4) serial antigen screening (ie, repeat antigen test 2 days after a negative result)., Results: Over 1 month, there were 77,980 admissions: 13.7% for COVID-19, 4.3% with but not for COVID-19, and 82.0% for non-COVID-19 indications without current infection. Without asymptomatic screening, 1,089 (credible interval [CI], 946-1,253) total SARS-CoV-2 infections (7.72%) went undetected. With 1-stage antigen screening, 734 (CI, 638-845) asymptomatic infections (67.4%) were detected, with 1,277 false positives. With combined antigen and PCR screening, 1,007 (CI, 875-1,159) asymptomatic infections (92.5%) were detected, with 5,578 false positives. A serial antigen testing policy detected 973 (CI, 845-1,120) asymptomatic infections (89.4%), with 2,529 false positives., Conclusions: Serial antigen testing identified >85% of asymptomatic infections and resulted in fewer false positives with less cost per identified infection compared to combined antigen plus PCR testing.

Background: Research trial participation may influence health outcomes regardless of the intervention assigned, but is often not assessed., Setting: We investigated how participation in an HIV prevention trial (the HIV Prevention Trials Network (HPTN) 068 study) affected health outcomes 4 years after the study in adolescent girls and young women in South Africa beyond effects of the tested intervention., Methods: We developed an analytical cohort that included the HIV Prevention 068 trial (HPTN 068) trial participants from the Agincourt Health and Demographic Surveillance System and resembled HPTN 068 trial enrollees (aged 13-20 years and in grades 8-11 in 2011) using inverse probability of treatment weights. We estimated risk differences for the association between trial participation and education and early parity (age <20 years) in 2019, after accounting for differences at baseline between the trial participants and nonparticipants., Results: There were 3442 young women enrolled in grades 8-11 in 2011; 1669 were in the HPTN 068 trial. Trial participants were more likely to have completed secondary school by 2019 (adjusted RD (aRD) 5.0%, 95% confidence interval (CI) 2.2%, 7.9%; 82.3% in trial participants vs. 77.2% in nonparticipants). Trial participants had similar risk of parity before age 20 compared with nontrial participants (aRD 2.3%, 95% CI: -0.8%, 5.5%)., Conclusions: Trial participation did not seem to influence early parity, but did increase educational attainment. Our results are compatible with an explanation of Hawthorne effects from trial participation on schooling behaviors that were small, but observable even 4 years after the end of the trial., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adolescent girls and young women (AGYW) living with HIV who have higher stress levels may be at risk of stress-related biological alterations, which could influence HIV progression and adherence to antiretroviral therapy (ART)., Setting: We aimed to estimate associations among stress-responsive biomarkers, ART adherence, and viral suppression in AGYW living with HIV in South Africa. We also hypothesized that psychosocial stressors [eg, depression, food insecurity, low socioeconomic status (SES), and HSV-2] would be associated with higher biomarker levels., Methods: We used 2018/2019 data from the HIV Prevention Trials Network 068 cohort to assess associations between stress-responsive biomarkers and viral suppression (<1000 copies/mL) and ART adherence measured using dried blood spot cards. Stress-responsive biomarkers included C-reactive protein, herpes simplex virus type 1, and cytomegalovirus infection and reactivation. Associations were estimated using unadjusted log-binomial or ordinal logistic regression models., Results: In 166 AGYW living with HIV, there was no association between stress-responsive biomarkers and viral suppression or ART adherence. However, increased C-reactive protein levels were associated with higher HSV-2 infection [odds ratio (OR) 1.98; 95% confidence interval (CI) 1.11, 3.52], being a government grant recipient (OR 3.21; 95% CI: 1.30, 7.92), lower food insecurity (OR 0.34; 95% CI: 0.13, 0.90), and increased body mass index (OR 1.07; 95% CI: 1.01, 1.14)., Conclusions: High prevalence of psychosocial stressors and persistent herpesviruses in AGYW living with HIV has the potential to lead to poorer health outcomes. More research is needed to untangle relationships between economic stability, chronic disease, and chronic stress., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Interventions for increasing the uptake of COVID-19 vaccination among Black young adults are central to ending the pandemic. Black young adults experience harms from structural forces, such as racism and stigma, that reduce receptivity to traditional public health messaging due to skepticism and distrust. As such, Black young adults continue to represent a priority population on which to focus efforts for promoting COVID-19 vaccine uptake., Objective: In aims 1 and 2, the Tough Talks digital health intervention for HIV disclosure will be adapted to address COVID-19 vaccine hesitancy and tailored to the experiences of Black young adults in the southern United States (Tough Talks for COVID-19). In aim 3, the newly adapted Tough Talks for COVID-19 digital health intervention will be tested across the following three southern states: Alabama, Georgia, and North Carolina., Methods: Our innovative digital health intervention study will include qualitative and quantitative assessments. A unique combination of methodological techniques, including web-based surveys, choose-your-own-adventures, digital storytelling, user acceptability testing, and community-based participatory approaches, will culminate in a 2-arm hybrid type 1 effectiveness implementation randomized controlled trial, wherein participants will be randomized to the Tough Talks for COVID-19 intervention arm or a standard-of-care control condition (N=360). Logistic regression will be used to determine the effect of the treatment arm on the probability of vaccination uptake (primary COVID-19 vaccine series or recommended boosters). Concurrently, the inner and outer contexts of implementation will be ascertained and catalogued to inform future scale-up. Florida State University's institutional review board approved the study (STUDY00003617)., Results: Our study was funded at the end of April 2021. Aim 1 data collection concluded in early 2022. The entire study is expected to conclude in January 2025., Conclusions: If effective, our digital health intervention will be poised for broad, rapid dissemination to reduce COVID-19 mortality among unvaccinated Black young adults in the southern United States. Our findings will have the potential to inform efforts that seek to address medical mistrust through participatory approaches. The lessons learned from the conduct of our study could be instrumental in improving health care engagement among Black young adults for several critical areas that disproportionately harm this community, such as tobacco control and diabetes prevention., Trial Registration: ClinicalTrials.gov NCT05490329; https://clinicaltrials.gov/ct2/show/NCT05490329., International Registered Report Identifier (irrid): DERR1-10.2196/41240., (©Henna Budhwani, Allysha C Maragh-Bass, Elizabeth E Tolley, Maria Leonora G Comello, Marie C D Stoner, Margo Adams Larsen, Donald Brambilla, Kathryn E Muessig, Audrey Pettifor, Christyenne L Bond, Christina Toval, Lisa B Hightow-Weidman. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.02.2023.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

ABSTRACT Stressful life circumstances (e.g. violence and poverty) have been associated with elevated biomarkers, including C-reactive protein (CRP), cytomegalovirus (CMV), and herpes simplex virus type-1 (HSV-1), among older adults in high-income settings. Yet, it remains unknown whether these relationships exist among younger populations in resource-limited settings. We therefore utilised a cohort of 1,279 adolescent girls and young women (AGYW) from the HIV Prevention Trials Network 068 study in rural South Africa to examine the associations between 6 hypothesized stressors (intimate partner violence (IPV), food insecurity, depression, socioeconomic status (SES), HIV, childhood violence) and 3 biomarkers that were measured using dried blood spots (CRP, CMV, and HSV-1). Ordinal logistic regression estimated the lagged and cross-sectional associations between each stressor and each biomarker. IPV was cross-sectionally associated with elevated CMV (OR = 2.45, 95% CI = 1.05,5.72), while low SES was cross-sectionally associated with reduced CMV (OR = 0.73, 95% CI = 0.58,0.93). AGYW with HIV had elevated biomarkers cross-sectionally (CRP: OR = 1.51, 95% CI = 1.08,2.09; CMV: OR = 1.86, 95% CI = 1.31,2.63; HSV-1: OR = 1.68, 95% CI = 1.17,2.41) and in a lagged analysis. The association between violence and CMV could help explain how violence results in stress and subsequently worse health among AGYW; however, additional research is needed to disentangle the longitudinal nature of IPV and stress.

We conducted a secondary analysis of discrete choice experiment (DCE) data from 395 couples enrolled in the Microbicide Trials Network (MTN)-045/CUPID study in Uganda and Zimbabwe to understand couple decision making around choice of multipurpose prevention technologies (MPTs) to prevent both HIV and pregnancy. Members of couples completed the same DCE, first separately then jointly, choosing between two hypothetical MPTs in a series of nine questions. Most couples either had similar preferences at the outset or had equal decision-making around MPTs (62%). Couples with male influence (17%) were more likely to use contraceptive pills with a male partner's knowledge and couples with female influence (21%) were less likely to have shared decision making about family planning. Males influenced discussion around MPT duration, side effects, menstrual changes, and how the vagina feels during sex. Decision making was relatively shared, though decisions around certain attributes were more likely to be dominated by male partners., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

End-user input early in biomedical product development may optimize design to support high uptake and adherence. We interviewed 400 couples (800 total participants) in Uganda and Zimbabwe to assess their preferences for multipurpose prevention technologies (MPTs) for HIV and pregnancy prevention. Using a discrete choice experiment, couples made a series of choices between hypothetical MPTs, including oral tablets and vaginal rings, inserts, and films and completed an interviewer-administered questionnaire assessing sociodemographic and behavioral measures. Most couples preferred presented MPTs over male condoms. Couples' MPT choices in both countries were influenced most by the combination of product form and dosing frequency, with monthly dosing preferred over daily. Analysis highlighted differences by country as to which side effects were most important: Ugandan couples placed greater importance on effects on the vaginal environment during sex, whereas Zimbabwean couples placed more importance on changes to menstruation and other side effects (headache, cramps). Couples' preferences signaled an openness to new product forms and more frequent dosing if preferred characteristics of other attributes were achieved., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: High social-emotional functioning, including emotion regulation and nonviolent conflict resolution, constitute developmental competencies of adolescence that promote health and well-being. We used prospective longitudinal data from a predominantly Latinx population to understand how family context and social environment risk factors for violence related to patterns of social-emotional functioning during the transition between middle school and high school., Methods: We prospectively interviewed 599 8th graders every 6 months for 2 years. We used trajectory models to explore longitudinal patterns of emotion regulation and nonviolent problem solving and multinomial regression to distinguish how these groups were associated with family context, partner and peer gang involvement, and neighborhood social disorder., Results: Youth reporting lower neighborhood disorder in 8th grade were more likely to be in the high emotion regulation trajectory group. Youth without exposure to gangs through peers and partners in 8th grade were more likely to be in the high nonviolent problem-solving skills trajectory group. Family cohesion was associated with being in the high trajectory groups for both emotional regulation and problem-solving skills., Conclusion: Emotion regulation and nonviolent problem-solving skills had different associations with the social environment risk factors for violence examined, indicating that mechanisms of influence and strategies for intervention may vary. The association between problem-solving skills and exposure to gangs through peers and partners shows that social norms may be important targets of change. Additionally, interventions with parents that build family cohesion during adolescence may buffer environmental exposures that shape adolescents' ability to practice protective social-emotional behaviors., (© 2022 The Foundation for Professionals in Services for Adolescents.)

Interactive stories are a relatively newer form of storytelling with great potential to correct misinformation while increasing self-efficacy, which is crucial to vaccine acceptance. To address COVID-19 vaccine hesitancy and medical mistrust in young Black adults (BYA), we sought to adapt a pre-existing application ("app"; Tough Talks) designed to address HIV disclosure decision-making through choose-your-own adventure (CYOA) narratives and other activities. The adapted app (Tough Talks - COVID) uses a similar approach to situate COVID-19 vaccination decision-making within social contexts and to encourage greater deliberation about decisions. To inform content for the CYOA narratives, we conducted an online survey that was used to elicit the behavioral, cognitive, and environmental determinants influencing COVID-19 vaccine hesitancy among 150 BYA (ages 18-29) in Georgia, Alabama, and North Carolina. The survey included scenario questions that were developed with input from a youth advisory board to understand responses to peer and family influences. In two scenarios that involved discussions with family and friends about vaccination status, most respondents chose to be honest about their vaccination status. However, vaccinated individuals perceived more social pressure and stigma about not being vaccinated than unvaccinated respondents who were not as motivated by social pressure. Personal choice/agency in the face of perceived vaccine risks was a more common theme for unvaccinated respondents. Results suggest that relying on changing social norms alone may not impact barriers to vaccination in unvaccinated young adults without also addressing other barriers to vaccination such as concerns about autonomy and vaccine safety. Based on these findings, CYOA narratives in the app were adapted to include discussions with family and friends but also to touch on themes of personal choice as well as other topics that influence behaviors besides norms such as safety, side effects, and risk of COVID-19 in an evolving pandemic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The HIV preexposure prophylaxis optimization intervention (PrEP-OI) study evaluated the efficacy of a panel management intervention using PrEP coordinators and a web-based panel management tool to support healthcare providers in optimizing PrEP prescription and ongoing PrEP care., Design: The PrEP-OI study was a stepped-wedge randomized clinical trial conducted across 10 San Francisco Department of Public Health primary care sites between November 2018 and September 2019. Each month, clinics one-by-one initiated PrEP-OI in random order until all sites received the intervention by the study team., Methods: The primary outcome was the number of PrEP prescriptions per month. Secondary outcomes compared pre- and postintervention periods on whether PrEP was discussed and whether PrEP-related counseling (e.g., HIV risk assessment, risk reduction counseling, PrEP initiation/continuation assessment) was conducted. Prescription and clinical data were abstracted from the electronic health records. We calculated incidence rate ratios (IRR) and risk ratios (RR) to estimate the intervention effect on primary and secondary outcomes., Results: The number of PrEP prescriptions across clinics increased from 1.85/month (standard deviation [SD] = 2.55) preintervention to 2.44/month (SD = 3.44) postintervention (IRR = 1.34; 95% confidence interval [CI] = 1.05-1.73; P  = 0.021). PrEP-related discussions during clinic visits (RR = 1.13; 95% CI = 1.04-1.22; P  = 0.004), HIV risk assessment (RR = 1.40; 95% CI = 1.14-1.72; P  = 0.001), and risk reduction counseling (RR = 1.16; 95% CI = 1.03-1.30; P  = 0.011) increased from the pre- to the postintervention period. Assessment of PrEP initiation/continuation increased over time during the postintervention period (RR = 1.05; 95% CI = 0.99-1.11; P  = 0.100)., Conclusions: A panel management intervention using PrEP coordinators and a web-based panel management tool increased PrEP prescribing and improved PrEP-related counseling in safety-net primary care clinics., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Young women in sub-Saharan Africa account for two-thirds of all new HIV infections and face high rates of unintended pregnancy. Multipurpose prevention technologies (MPTs) are promising products under development that are designed to simultaneously prevent HIV and unintended pregnancy. Since MPTs will be used in the context of sexual relationships, ensuring acceptability and use requires understanding the role of male partners in MPT use decision-making., Methods: This paper draws on qualitative data from 39 couples enrolled in the Microbicide Trials Network (MTN) 045 study, conducted in 2019-2020. Partners completed a discrete choice experiment (DCE), first separately and then jointly, to measure preferences for future MPT attributes and then completed a qualitative interview. We also draw on quantitative data from interviewer observation about who dominated the decision-making process during the joint DCE. Content analysis was used to examine (1) how couples made decisions on existing non-MPT HIV and pregnancy prevention products; (2) how couples made decisions on future ideal-MPT product during the DCE; and (3) how these decision-making processes varied by decision-making dominance (10 male, 10 female and 19 equal) and interview type (19 joint and 20 separate)., Results: Existing non-MPT product decisions focused on trust between partners and product attributes, while future ideal-MPT product decisions exclusively focused on product attributes. Across existing and future products, preferences for product attributes varied by gender. Male partners were most concerned with limiting side effects impacting sexual pleasure, female partners were most concerned with limiting side effects causing physical symptoms and both were concerned with the return to fertility. Across all dominance and interview types, couples reported making decisions together and female partners were often able to negotiate with male partners for their preferred product or set of product attributes., Conclusions: Research activities in this study provided an opportunity for couples to openly present their product attribute preferences to their partner, learn about their partner's attribute preferences, negotiate for their ideal set of attributes and ultimately choose attributes that benefited the couple without disempowering the female partner. Future research should focus on the utility of couple-based decision-making aids or similar tools for facilitating joint MPT decision-making., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Young women who sell sex (YWSS) are at heightened risk of HIV acquisition and transmission and are among the least engaged in HIV services. There is insufficient epidemiologic evidence characterizing the burden of HIV among YWSS, particularly as compared to older WSS. These data are needed to design and tailor effective HIV prevention and treatment programmes for this population., Methods: We conducted two parallel systematic reviews and meta-analyses to define both the immediate and long-term HIV risks for YWSS, including among women engaged in sex work, survival sex and transactional sex. In the first review, we identified and synthesized published studies of HIV incidence comparing estimates for cisgender women ≤24 years of age versus &gt;24. In the second review, we identified and synthesized studies of HIV prevalence, comparing estimates for cisgender women who initiated selling sex &lt;18 versus ≥18 years. In both reviews, we completed a search of four databases for articles in any language and any geographic area published from 1 January 1980 until 12 February 2021. Included articles were assessed for quality and a random effects model was used to calculate pooled effect estimates for each review., Results and Discussion: We identified 12 studies for the HIV incidence review and 18 studies for the HIV prevalence review. In a meta-analysis, HIV incidence was elevated in younger (5.3 per 100 person-years [PY]; 95% confidence interval [CI]: 3.5, 7.1) compared to older women (2.8 per 100 PY; 95% CI: 1.7, 3.9), although CIs overlapped. HIV prevalence among those who initiated selling sex &lt;18 years of age (28.8; 95% CI: 18.9, 38.7) was higher than those who initiated later (20.5; 95% CI: 12.4, 28.6)., Conclusions: These companion reviews offer an important perspective on the relative HIV risk of engaging in selling sex at a younger age. Our findings highlight the unique and intersectional challenges YWSS face, and the importance of ensuring that health services are tailored to meet their specific needs. Research and programming should routinely stratify data into meaningful age bands to differentiate and intervene within this population., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Technology-based directly observed therapy (DOT) is more cost-effective and efficient compared with in-person monitoring visits for medication adherence. While some evidence shows these technologies are feasible and acceptable, there is limited evidence collating information across medical conditions or in the context of HIV prevention, care, and treatment. Objectives: We conducted a scoping review to understand the current evidence on the acceptability, feasibility, and efficacy of digital DOT to improve medication adherence and, specifically, to determine if digital DOT had been used to improve adherence for HIV prevention, care, and treatment Methods: We searched the electronic databases PubMed, Embase, and the Web of Science in January 2021 for any published studies with terms related to digital technologies and DOT. We included peer-reviewed studies in any population, from any country, for any outcome, and excluded conference abstracts. We included three types of digital DOT interventions: synchronous DOT, asynchronous DOT, and automated DOT. We provide an assessment of the current evidence, gaps in literature, and opportunities for intervention development regarding the use digital DOT to improve antiretroviral therapy (ART) adherence, specifically in the field of HIV. Results: We identified 28 studies that examined digital DOT. All studies found digital DOT to be acceptable and feasible. Patients using digital DOT had higher rates of treatment completion, observed doses, and adherence compared with in-person DOT, although data were limited on adherence. Only one study examined HIV prevention, and none examined ART adherence for HIV treatment. Conclusions: Digital DOT is acceptable and feasible but has not been used to remotely monitor and support ART adherence for people living with HIV.

Purpose: In South Africa, adolescent mothers have a three times higher risk of HIV acquisition than nonadolescent mothers. Yet, limited evidence exists regarding how early childbearing may affect HIV risk. A better understanding of adolescent mothers' partnership dynamics and sexual behaviors is critical to tailoring interventions to prevent new infections., Methods: Data are from HIV Prevention Trials Network 068, a longitudinal study of adolescent girls and young women (AGYW) aged 13-20 in South Africa who were followed annually for up to 6 years. Log-binomial regression models were used to assess whether adolescent motherhood was associated with partnership dynamics (intimate partner violence, gender inequitable norms, low relationship power, no HIV prevention communication) and if the association between partnership dynamics and sexual behaviors (unprotected sex and transactional sex) varied by adolescent motherhood. Generalized estimating equations, with an exchangeable correlation structure, were used to account for nonindependence., Results: Adolescent mothers were more likely than nonadolescent mothers to be in partnerships characterized by intimate partner violence, low relationship power, gender inequitable norms, and no HIV prevention communication. A higher proportion were also more likely to experience these dynamics, as well as engage in transactional sex, after giving birth. Poor partnership dynamics put AGYW at a higher risk for unprotected sex and transactional sex, regardless of adolescent motherhood status., Discussion: Engaging adolescent mothers in interventions post birth and developing interventions that address power imbalances in AGYW's sexual partnerships have the potential to reduce engagement in HIV-related sexual behaviors and HIV risk in the long term., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Adolescents and young adults (AYA; 13-24 years-old) comprise 22% of new HIV infections in the United States (US), most of whom live in the South. We used the situated-Information, Motivation, Behavioral skills (sIMB) model to identify priorities for intervention on multi-level factors that influence HIV preventive care among Black AYA in Durham, North Carolina. We conducted two participatory workshops (ages 13-17, N = 6; ages 18-24, N = 7) to engage youth about how to discuss HIV. We also assessed sIMB constructs from a separate quantitative sample of youth to contextualize the workshop findings (N = 80). HIV knowledge was low overall, but lower among younger Black AYA, suggesting a need for comprehensive sexual education. Trusted adults provided sexual health information, motivation for health maintenance, and behavioral skills support. HIV prevention interventions should provide comprehensive sexual health education to Black AYA, be age-specific, and include social supporters like parents, teachers, and community members., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Adolescent motherhood is common in South Africa and occurs against a backdrop of high HIV risk. While childbearing during adolescence may result in social and economic strain that may negatively impact health, there has been limited study of whether adolescent motherhood increases the risk of HIV or herpes simplex virus type 2 (HSV-2) acquisition or engagement in high-risk sexual partnerships., Setting: Data are from HIV Prevention Trials Network 068, a longitudinal conditional cash transfer study of adolescent girls and young women (age, 13-23) in rural South Africa., Methods: We used survival analysis to estimate hazard ratios to determine if adolescent motherhood (live birth before 20 years) predicted incident HIV and incident HSV-2 and generalized estimating equations for behavioral risk ratios to determine if adolescent motherhood was associated with transactional sex and age-disparate partnerships., Results: Of 2452 adolescent girls and young women who were HIV negative at baseline, 5% were adolescent mothers; 16% were adolescent mothers by the end of the study period. After controlling for covariates, adolescent motherhood predicted incident HSV-2 acquisition [ adjusted hazard ratios, 1.30; 95% confidence interval (CI): 1.01 to 1.95] but not HIV acquisition ( adjusted hazard ratios, 1.19; 95% CI, 0.76 to 1.86). Adolescent motherhood was also associated with being in an age-disparate partnership (adjusted risk ratio, 1.30; 95% CI: 1.07 to 1.58) but not transactional sex., Conclusion: Adolescent motherhood increased the risk of HSV-2 and engagement in age-disparate partnerships, both known risk factors for HIV infection. Sexually transmitted infection screening and/or tailored combination HIV prevention interventions that account for the context of adolescent motherhood are critical to maximize adolescent mothers' long-term health and to meet UNAIDS 95-95-95 targets by 2030., Competing Interests: N.L.B. was supported by the National Institute of Allergy and Infectious Diseases (T32 AI00700140). The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Public health decision makers rely on hospitalization forecasts to inform COVID-19 pandemic planning and resource allocation. Hospitalization forecasts are most relevant when they are accurate, made available quickly, and updated frequently. We rapidly adapted an agent-based model (ABM) to provide weekly 30-day hospitalization forecasts (i.e., demand for intensive care unit [ICU] beds and non-ICU beds) by state and region in North Carolina for public health decision makers. The ABM was based on a synthetic population of North Carolina residents and included movement of agents (i.e., patients) among North Carolina hospitals, nursing homes, and the community. We assigned SARS-CoV-2 infection to agents using county-level compartmental models and determined agents' COVID-19 severity and probability of hospitalization using synthetic population characteristics (e.g., age, comorbidities). We generated weekly 30-day hospitalization forecasts during May-December 2020 and evaluated the impact of major model updates on statewide forecast accuracy under a SARS-CoV-2 effective reproduction number range of 1.0-1.2. Of the 21 forecasts included in the assessment, the average mean absolute percentage error (MAPE) was 7.8% for non-ICU beds and 23.6% for ICU beds. Among the major model updates, integration of near-real-time hospital occupancy data into the model had the largest impact on improving forecast accuracy, reducing the average MAPE for non-ICU beds from 6.6% to 3.9% and for ICU beds from 33.4% to 6.5%. Our results suggest that future pandemic hospitalization forecasting efforts should prioritize early inclusion of hospital occupancy data to maximize accuracy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Given challenges with adherence to existing HIV prevention products, the development of an extended duration vaginal ring could improve adherence while reducing patient and provider burden. Additionally, women have other interlinked sexual health concerns such as unintended pregnancy. We evaluated acceptability of a 90-day ring to prevent HIV and hypothetical preferences for a dual (HIV and contraceptive) indication. This was a secondary analysis of a Phase 1, two-arm, multi-site, placebo-controlled randomized trial evaluating safety and pharmacokinetics of a 90-day vaginal ring containing tenofovir for HIV prevention (N = 49). We used a mixed methods approach to assess quantitative data on acceptability (n = 49) and used qualitative data from a random subset to explain the quantitative findings (N = 25). The 3-month extended duration tenofovir ring was highly acceptable. Participants perceived the ring to be easy to use, comfortable and reported liking it more over time. About half felt the ring during sex but most of those participants said it bothered them only a little. Concerns about hygiene increased over the study period but were often outweighed by the benefits of an extended duration ring. Interest in a multi-purpose ring was high (77%) and even higher among those who were sexually active and had male partners. The 3-month extended duration tenofovir ring for HIV prevention was highly acceptable among women and interest in an MPT was high., Competing Interests: Dr. Chen receives research grants from Medicines360 and Sebela, which are all managed by Magee-Womens Research Institute. All other authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective To study eight types of sexual assault among cisgender women, cisgender men and gender minority college students, estimating the prevalence of perpetration by persons of particular gender identities. Participants and Methods: 13,685 sexual assault survivors were surveyed. For each type of sexual assault victimization experienced by cisgender women, cisgender men and gender minorities, prevalence estimates assessed the extent of perpetration by persons of each gender identity. Results: Cisgender men were the most prevalent perpetrators of all types of sexual assault against cisgender women and gender minorities. Cisgender women were the most prevalent perpetrators of five types of sexual assault against cisgender men, with cisgender women and cisgender men being similarly likely to perpetrate three types of sexual assault against cisgender men. Conclusions: Cisgender men perpetrate most sexual assaults against cisgender women and gender minority students; cisgender women and cisgender men perpetrate most sexual assaults against cisgender men students.

Background: Information is needed to monitor progress toward a level of population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sufficient to disrupt viral transmission. We estimated the percentage of the US population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021., Methods: Publicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates with a range of population immunity thresholds., Results: In our main analysis, which was the most optimistic scenario, presumed population immunity varied among states (43.1% to 70.6%), with 19 states with ≤60% of their population having been infected or vaccinated. Four states had presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (≥78%)., Conclusions: The United States remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

We analyzed data from 1428 users of the dapivirine vaginal ring, who participated in the MTN-020/ASPIRE phase III trial and subsequent open-label extension MTN-025/HOPE trial, to examine relationships between perceived ring protection, social disclosures, and self-reported ring adherence. In HOPE, 77% perceived the ring to be highly effective, and this view was associated with speaking: (a) to a greater number of people about the study, (b) with other participants, (c) to more people who were in favor of the ring, and (d) to more people whose opinions were valued. Reported adherence was not directly associated with perceived protection but was associated with disclosing to someone who was in favor of the ring. These findings suggest the importance of women's internalized ideas about the protective benefits of the DVR in sharing information about the ring and the importance of social support on adherence., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Given the success of cash programs in improving health outcomes and addressing upstream drivers of HIV risk such as poverty and education, there has been an increasing interest in their potential to improve HIV prevention and care outcomes. Recent reviews have documented the impacts of structural interventions on HIV prevention, but evidence about the effects of cash transfer programs on HIV prevention has not been systematically reviewed for several years., Methods and Findings: We did a systematic review of published and unpublished literature to update and summarize the evidence around cash programs for HIV prevention from January 2000 to December 17, 2020. We included studies with either a cash transfer intervention, savings program, or program to reduce school costs. Included studies measured the program's impact on HIV infection, other sexually transmitted infections (STIs), or sexual behaviors. We screened 1,565 studies and examined 78 in full-text review to identify a total of 45 peer-reviewed publications and reports from 27 different interventions or populations. We did not do a meta-analysis given the range of outcomes and types of cash transfer interventions assessed. Most studies were conducted in sub-Saharan Africa (N = 23; South Africa, Tanzania, Malawi, Lesotho, Kenya, Uganda, Zimbabwe, Zambia, and eSwatini) followed by Mexico (N = 2), the United States (N = 1), and Mongolia (N = 1)). Of the 27 studies, 20 (72%) were randomized trials, 5 (20%) were observational studies, 1 (4%) was a case-control study, and 1 (4%) was quasi-experimental. Most studies did not identify a strong association between the program and sexual behaviors, except sexual debut (10/18 finding an association; 56%). Eight of the 27 studies included HIV biomarkers, but only 3 found a large reduction in HIV incidence or prevalence, and the rest found no statistically significant association. Of the studies that identified a statistically significant association with other STIs (N = 4/8), 2 involved incentives for staying free of the STI, and the other 2 were cash transfer programs for adolescent girls that had conditionalities related to secondary schooling. Study limitations include the small number of studies in key populations and examining interventions to reduce school costs and matched saving programs., Conclusions: The evidence base for large-scale impacts of cash transfers reducing HIV risk is limited; however, government social protection cash transfer programs and programs that incentivize school attendance among adolescent girls and young women show the greatest promise for HIV prevention., Competing Interests: The authors have declared that no competing interests exist.

Poverty alleviation programs can reduce HIV incidence but may have greater impacts when combined with other psychosocial interventions. We modeled the change in HIV incidence among South African adolescent girls and young women (AGYW) associated with combining a cash transfer (the South African Child Support Grant (CSG)) with other structural and behavioral interventions. We modeled observational data from the HPTN 068 study where 2328 HIV negative AGYW (13-20 years) were followed for 4 years. In a Monte Carlo simulation based on this cohort (N = 10,000), CSG receipt was not independently associated with HIV incidence. Providing the CSG combined with increasing caregiver care and reducing adolescent depression had the largest reduction in HIV incidence with the fewest number of combined interventions (RD - 3.0%; (95% CI - 5.1%, - 0.9%). Combining a monthly grant with interventions to increase caregiver care and reduce adolescent depression could substantially reduce HIV incidence above the provision of cash alone., (© 2021. The Authors.)

Background: Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV., Methods: We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors., Results: Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, -1.4%; 95% confidence interval [CI], -2.7% to -.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by -1.3% (95% CI, -2.6% to -.2%)., Conclusions: To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Despite demonstrated efficacy for HIV prevention, substantial challenges remain for the successful rollout of oral pre-exposure prophylaxis (PrEP), especially among adolescent girls and young women (AGYW). We characterized trajectories of PrEP adherence among 200 AGYW in South Africa and analyzed data from 22 qualitative interviews and 3 focus group discussions for explanatory purposes. Two adherence trajectory groups were identified: 52% with high early adherence that declined after month three and 48% with low adherence throughout. Adherence in the "consistently low" group was related to social support and logistical concerns, while the decrease in the "high declining" group corresponded to a change in the frequency of study visits from monthly to quarterly. PrEP support should be differentiated for those who need more frequent visits and adherence support initially versus later in PrEP use. Visits every month, when needed, should be considered for AGYW who need sustained support later into use.

Background: As adolescent girls and young women (AGYW) transition to adulthood, their interaction with their social context becomes a critical consideration for HIV prevention interventions. Few studies have examined what types of community groups and community spaces might be protective for AGYW HIV acquisition and related sexual behaviors., Methods: Data were obtained from HIV Prevention Trials Network 068, a longitudinal study of AGYW (age 13-20 years) in rural South Africa. Survival analyses and generalized estimating equations were used to assess whether community group membership and time spent in community spaces were associated with HIV incidence and sexual behaviors (unprotected sex, transactional sex, and having an older partner)., Results: A total of 2245 AGYW were followed up for up to 4 years. Membership in church groups [adjusted hazard ratio (aHR): 0.75, 95% confidence interval (CI): 0.53 to 0.91] and dance groups (aHR: 0.89, 95% CI: 0.80 to 0.98) and spending time at church (aHR: 0.88, 95% CI: 0.79 to 0.98) were protective for HIV infection. Conversely, spending time at taverns was associated with higher HIV incidence (aHR: 1.27, 95% CI: 1.15 to 1.41). Membership in church groups and spending time at a family member's home and at church were protective for all 3 sexual behaviors. Spending time at a boyfriend's home and taverns was risky for all 3 sexual behaviors., Conclusions: The results suggest that community spaces and community groups that include an element of adult supervision are potentially protective, whereas spaces and groups that provide an opportunity for AGYW to interact unsupervised with boyfriends or meet new partners are potentially risky., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Evidence on cash transfer interventions for HIV prevention in adolescent girls and young women is unclear and indicates that they may not work uniformly in all settings. Qualitative interviews were conducted with 22 girls and young women post-intervention to determine how a cash transfer study (HPTN 068) in South Africa was perceived to influence sexual behaviours and to explore mechanisms for these changes. Participants described how the intervention motivated them to increase condom use, have fewer partners, end risky relationships and access HIV testing services at local primary health clinics. Changes were attributed to receipt of the cash transfer, in addition to HIV testing and sexual health information. Processes of change included improved communication with partners and increased negotiation power in sexual decision-making. Economic empowerment interventions increase confidence in negotiating behaviours with sexual partners and are complementary to sexual health information and health services that provide young women with a foundation on which to make informed decisions about how to protect themselves.

Background: Nearly all population-level research showing positive associations between age-disparate partnerships and HIV acquisition among adolescent girls and young women (AGYW) has classified age disparity as ≥5 or ≥10 years. We describe variations in 1-year risk of HIV infection after exposure to sexual partner(s) of continuous age disparities., Methods: Longitudinal data from the HPTN 068 randomized trial in South Africa were used to estimate 1-year risk of HIV infection at various age pairings. The parametric g-formula was used to estimate risk at up to 5 annual time points, stratified by maximum partner age difference, maximum partner age, and AGYW age., Results: AGYW reported an older partner in 86% of 5351 age pairings. The 1-year risk of HIV infection rapidly increased with maximum partner age difference among girls ages 13-14 years, from 0·01 with a same-age partner, to 0·21 with a partner 10 years older, and 0·24 with a partner 15 years older. A gradual increase occurred among AGYW ages 15-16 years, up to 0·13 with a partner 15 years older, and 0·09 among AGYW 17-18 years with partners 8-11 years older. Risk of HIV infection among AGYW ages 19-21 years remained relatively constant across maximum partner age differences., Conclusions: Age differences between AGYW and their sexual partners have a greater effect on HIV-risk infection in younger compared with older AGYW. Considering both the age of an AGYW and her sexual partners provides granular insight into identifying key groups for HIV transmission prevention efforts.

Objective: In sub-Saharan Africa, transactional sex is associated with an increased risk of HIV infection in adolescent girls and young women, but the mechanisms for this relationship remain unclear. We hypothesize that young women who report transactional sex may have multiple partners and older partners, thereby increasing their HIV risk., Setting: We used longitudinal data from the HPTN 068 trial in rural South Africa where young women aged 13-20 who were HIV-negative at enrolment (n = 2362) were followed approximately annually for up to 6 years., Methods: We used the parametric g-formula to estimate the total effect of time-varying, frequent transactional sex (receipt of gifts/money at least weekly versus monthly or less) on HIV incidence and the controlled direct effect for mediation in a simulated cohort using 20,000 bootstrapped observations. We calculated rates and hazard ratios (HRs) over the entire study period., Results: The HR for the total effect of frequent transactional sex on HIV incidence was 1.56 (95% confidence interval: 1.28 to 1.85). However, this effect was mediated by partner age (>5+) and number of partners (>1) and the HR was attenuated to 1.09 (95% confidence interval: 0.90 to 1.28) when setting both partner age and partner number constant., Conclusion: Both partner age difference and partner number mediate the relationship between transactional sex and incident HIV infection. Through this mediation analysis, we provide important longitudinal evidence to suggest that young women who engage in frequent transactional sex select multiple partners, often older male partners that may be part of higher risk sexual networks.

Purpose: Schooling is associated with a lower risk of Herpes simplex virus type 2 (HSV-2) in adolescent girls and young women, but there is little understanding of the pathways underlying this relationship., Methods: We used data from adolescent girls and young women in South Africa enrolled in the HIV Prevention Trials Network 068 study. We tested a structural equation model where individual household and community education measures were associated directly and indirectly with incident HSV-2 through HIV knowledge, future aspirations, age-disparate partnerships, sex in the last 12 months, and condomless sex., Results: Community, household, and individual measures of schooling were all associated with incident HSV-2 infection through mediated pathways that increased the likelihood of having sex. Low school attendance (<80% of school days) increased the likelihood of having sex through increased age-disparate partnerships and reduced future aspirations. Fewer community years of education increased the likelihood of having sex through increased age-disparate partnerships. Parental education level was indirectly associated with HSV-2 overall, although we could not identify the individual pathways that were responsible for this association., Conclusions: Community and individual schooling interventions may reduce the risk of HSV-2 infection by influencing the likelihood of having sex, partner age, and future aspirations., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Transactional sex is associated with socioeconomic disadvantage and HIV risk but few studies in the United States (US) have examined both individual and area-level predictors of transactional sex or distinguished transactional sex from sex work. We combined data from HIV Prevention Trials Network 064 study and the US Census to estimate prevalence ratios (PR) for the relationship between census-level and individual measures of economic deprivation and housing instability on transactional sex in 417 women in North Carolina. Increased transactional sex was associated with food insecurity (PR 1.86; 95%; CI 1.57, 2.19), housing instability (PR 1.33; 95% CI 1.11, 1.59), substance abuse (PR 1.90; 95% CI 1.64, 2.19) and partner incarceration (PR 1.32; 95% CI 1.09, 1.61). Census-level indicators were not associated with transactional sex, adjusted for individual-level covariates. Interventions should support housing stability and financial opportunities among southern African American women to reduce HIV risk, particularly among women with incarcerated partners.

Background . Prevention of both school dropout and teen pregnancy represent clear public health priorities for South Africa, yet their complex and potentially cyclical relationship has not been fully explored. Objective . To further understand how this relationship operates, we analyzed data from a randomized trial of young women aged 13 to 20 years enrolled in school in rural South Africa to estimate the association between pregnancy and subsequent dropout and between dropout and subsequent pregnancy. Method . We examined inverse probability (IP) of exposure-weighted survival curves for school dropout by pregnancy and for pregnancy by school dropout. We used weighted curves to calculate 1-, 2-, and 3-year risk differences and risk ratios. Additionally, we used an IP-weighted marginal structural cox model to estimate a hazard ratio (HR) for each relationship. Results . Dropout from school was associated with subsequent pregnancy (HR 3.58; 95% confidence interval [CI] [2.04, 6.28]) and pregnancy was associated with subsequent school dropout (HR 2.36; 95% CI [1.29, 4.31]). Young women who attended school but attended fewer days had a higher hazard of pregnancy than those who attended more school (HR 3.64; 95% CI [2.27, 5.84]). Conclusion . Pregnancy is both a cause and a consequence of school dropout. Consideration of school attendance and academic performance could ultimately enhance pregnancy prevention efforts in this population. Programs should be tailored differently for (1) girls who have dropped out of school, (2) those who are in school and at risk for pregnancy, and (3) those who are in school and become pregnant.