Developmental Trajectories of Transactional Sex and Age-Disparate Relationships During Adolescence: An HPTN 068 Analysis.

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.

Development and validation of the mpox stigma scale (MSS) and mpox knowledge scale (MKS).

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 (χ2(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 (χ2(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.

Transgender-Specific Differentiated HIV Service Delivery Models in the South African Public Primary Health Care System (Jabula Uzibone): Protocol for an Implementation Study.

BACKGROUND: Almost 60% of transgender people in South Africa are living with HIV. Ending the HIV epidemic will require that transgender people successfully access HIV prevention and treatment. However, transgender people often avoid health services due to facility-based stigma and lack of availability of gender-affirming care. Transgender-specific differentiated service delivery (TG-DSD) may improve engagement and facilitate progress toward HIV elimination. Wits RHI, a renowned South African research institute, established 4 TG-DSD demonstration sites in 2019, with funding from the US Agency for International Development. These sites offer unique opportunities to evaluate the implementation of TG-DSD and test their effectiveness. OBJECTIVE: The Jabula Uzibone study seeks to assess the implementation, effectiveness, and cost of TG-DSD for viral suppression and prevention-effective adherence. METHODS: The Jabula Uzibone study collects baseline and 12-month observation checklists at 8 sites and 6 (12.5%) key informant interviews per site at 4 TG-DSD and 4 standard sites (n=48). We seek to enroll ≥600 transgender clients, 50% at TG-DSD and 50% at standard sites: 67% clients with HIV and 33% clients without HIV per site type. Participants complete interviewer-administered surveys quarterly, and blood is drawn at baseline and 12 months for HIV RNA levels among participants with HIV and tenofovir levels among participants on pre-exposure prophylaxis. A subset of 30 participants per site type will complete in-depth interviews at baseline and 12 months: 15 participants will be living with HIV and 15 participants will be HIV negative. Qualitative analyses will explore aspects of implementation; regression models will compare viral suppression and prevention-effective adherence by site type. Structural equation modeling will test for mediation by stigma and gender affirmation. Microcosting approaches will estimate the cost per service user served and per service user successfully treated at TG-DSD sites relative to standard sites, as well as the budget needed for a broader implementation of TG-DSD. RESULTS: Funded by the US National Institutes of Mental Health in April 2022, the study was approved by the Human Research Ethics Committee at University of Witwatersrand in June 2022 and the Duke University Health System Institutional Review Board in June 2023. Enrollment began in January 2024. As of July 31, 2024, a total of 593 transgender participants have been enrolled: 348 are living with HIV and 245 are HIV negative. We anticipate baseline enrollment will be complete by August 31, 2024, and the final study visit will take place no later than August 2025. CONCLUSIONS: Jabula Uzibone will provide data to inform HIV policies and practices in South Africa and generate the first evidence for implementation of TG-DSD in sub-Saharan Africa. Study findings may inform the use of TG-DSD strategies to increase care engagement and advance global progress toward HIV elimination goals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64373.

Oral SARS-CoV-2 host responses predict the early COVID-19 disease course.

Oral fluids provide ready detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to evaluate relationships between oral virus, oral and systemic anti-SARS-CoV-2-specific antibodies, and symptoms. Oral fluids (saliva/throat wash (saliva/TW)) and serum were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+ human participants (n = 45). SARS-CoV-2 RT-qPCR and N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR for subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA and ELISA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. At time of enrollment (baseline, BL), LFA-detected N-antigen in 86% of TW and was immunoblot-confirmed. However, only 3/17 were saliva/TW qPCR+ . Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three anti-spike sero-negative participants suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19-29aa, RMSD 1-1.5 Angstroms). At enrollment, symptomatic participants demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (63%/54%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral and serum IgG correlated 100% with NP+ PCR status. Cough and fatigue severity (p = 0.010 and 0.018 respectively), and presence of weakness, nausea, and composite upper respiratory symptoms (p = 0.037, 0.005, and 0.017, respectively) were negatively associated with saliva IgM but not TW or serum IgM. Throat wash IgM levels were higher in women compared to men, although the association did not reach statistical significance (median: 290 (female) versus 0.697, p = 0.056). Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms and early oral IgM responses during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.

Patterns and predictors of COVID-19 vaccination among young adults at 44 US sites: Secondary analysis of a randomized, controlled, open-label trial, March - December 2021.

BACKGROUND: The introduction of vaccines during the COVID-19 pandemic provided an opportunity to slow transmission of SARS-CoV-2, but initial uptake of COVID-19 vaccination was slow. We analyzed data from a randomized clinical trial of the mRNA-1273 vaccine (NCT04811664) to describe the patterns of uptake of COVID-19 vaccines among young adults. METHODS: The CoVPN 3006 trial randomized adults ages 18-29 from 44 sites in the United States to receive 1) immediate mRNA-1273 vaccination from the study site, or 2) standard of care, including the option to seek vaccination at any time in the future. Randomization occurred between March and November 2021, and an observational arm of adults who declined vaccination was enrolled beginning June 2021. Among participants in the standard of care (SoC) or Vaccine Declined arms, we estimated demographic, behavioral, and health history correlates of vaccination, and the four-month cumulative incidence of COVID-19 vaccination using inverse probability weighted Kaplan-Meier estimators. RESULTS: Among 728 SoC and 470 Vaccine Declined participants, 79% and 16% received COVID-19 vaccination, respectively. SoC and Vaccine Declined participants were more likely to seek and receive vaccination if they reported COVID-19 preventive behaviors, including wearing masks, physically distancing, and avoiding large gatherings. We identified strong predictors of vaccination in the Vaccine Declined arm, including attending class in person (adjusted risk ratio [aRR]: 0.47, 95% confidence interval [CI] 0.21, 1.03), having a COVID-19 relevant medical condition (aRR: 1.95, 95% CI: 0.89, 4.26), and avoiding large gatherings (aRR: 2.24, 95% CI: 1.18, 4.25), though low vaccination rates in this arm led to imprecise estimates. CONCLUSIONS: Individuals who initially decline vaccination can be convinced to vaccinate, particularly if they are already practicing other forms of COVID-19 prevention. Continued outreach and education from the scientific community can combat low vaccine confidence.

Elevated stress-responsive biomarkers are associated with HIV acquisition in young women in rural South Africa: A HPTN 068 case cohort study.

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% 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.

COVID-19-related stigma within a rural South African community: A mixed methods analysis.

BACKGROUND: Infectious disease-related stigma is a pervasive global issue that impedes disease control efforts by increasing reluctance to seek treatment or engagement in prevention behaviors for fear of ostracism. Despite this, there is limited research on COVID-19 stigma in Africa, specifically rural South Africa, which has faced infectious disease-related stigma throughout the HIV epidemic. METHODS: Population-based surveys were conducted among 1,662 adults living in the Agincourt Health and Socio-Demographic Surveillance System (AHDSS) area in Mpumalanga, South Africa, in August-October 2020 and August-October 2021. Surveys measured anticipated COVID-19-related stigma from low to high levels. Changes in stigma between surveys were compared using Wilcoxon ranked sign tests, and log-binomial models estimated the association between socio-demographic factors and anticipated stigma at both intervals. Qualitative interviews were conducted in 2022 among 31 adults who completed the original surveys, and the data were analyzed thematically to describe anticipated, perceived, and enacted stigma. RESULTS: Anticipated stigma significantly decreased from the first to the second survey (p-value:<0.0001). Stigma was significantly higher among older age groups. In 2020, those less knowledgeable about COVID-19 were 2.24 times as likely to have higher levels of anticipated stigma compared to those who were more knowledgeable (RR:2.24, 95% CI: 1.90,2.64). Fear of being stigmatized influenced willingness to disclose infection. Participants perceived COVID-19 stigma as similar to HIV/AIDS stigma, but concern and fear reduced over time, with differences observed across generations and sexes. For some, fear of death and mistrust of others endorsed enacting stigma toward others. CONCLUSION: While COVID-19 stigma decreased over time in rural South Africa, different forms of stigma persisted and influenced participants' willingness to reveal their COVID-19 infection status. Given South Africa's history with infectious disease-related stigma hindering public health efforts, it is crucial that government bodies prioritize strategies to mitigate stigma in rural communities.

Exploring the Relationship Between Anticipated Stigma and Community Shared Concerns about HIV on Defaulting from HIV Care in Rural South Africa.

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.

The effect of youth-friendly health services on risk of pregnancy among adolescent girls and young women in Lilongwe, Malawi: a secondary analysis of the girl power-Malawi study.

In sub-Saharan Africa, adolescent girls and young women aged 15-24 (AGYW) experience high risk of early and unintended pregnancy. We assessed the impact of youth-friendly health services (YFHS) on pregnancy risk among AGYW who participated in the Girl Power study. In 2016, Girl Power randomly assigned four government-run health centers in Lilongwe, Malawi, to provide a standard (n=1) or youth-friendly (n=3) model of service delivery. At six and 12 months, study participants (n=250 at each health center) self-reported their current pregnancy status and received a urine pregnancy test. Because of missing pregnancy test results, we used multiple imputation to correct for outcome misclassification in self-reported pregnancy status, and applied the parametric g-formula on the corrected data to estimate the effect of YFHS on the 12-month risk of pregnancy. After correcting for outcome misclassification, the risk of pregnancy under the scenario where all health centers offered YFHS was 15.8% compared to 23.2% under the scenario where all health centers offered standard of care (risk difference: -7.3%, 95% CI: -15.5%, 0.8%). Access to a model of YFHS that integrates provider training with youth-friendly clinic modifications and community outreach activities may decrease risk of pregnancy among AGYW relative to standard of care.

The relationship between anti-LGBTQ+ legislation and HIV prevention among sexual and gender minoritized youth.

OBJECTIVE: The aim of this study was to estimate the longitudinal associations of state-level anti-LGBTQ+ policies and county-level politics with individual HIV prevention outcomes among sexual and gender minoritized (SGM) youth. DESIGN: Keeping it LITE-1 prospectively enrolled 3330 SGM youth and young adults (ages 13-34) at increased risk of HIV throughout the United States from 2017 to 2022. METHODS: Semiannual surveys collected self-reported HIV prevention measures [current preexposure prophylaxis (PrEP) use, weekly PrEP adherence, HIV/STI testing in the past 6 months]. Geolocation was linked with state-level LGBTQ+ policy data and county-level election data. Generalized linear models with GEE estimated the single and joint longitudinal associations for two exposures [state-level policy climate (more discriminatory vs. less discriminatory) and county-level political majority (Democratic/swing vs. Republican)] with each outcome. RESULTS: Among participants living in a state with more discriminatory laws, those in a Democratic/swing county had a 6-percentage point increase in PrEP use (95% confidence interval: 0.02, 0.09) compared to those in a Republican county. Those living in a Republican county but a state with less discriminatory laws saw a similar increase (0.05; -0.02,0.11). Residing in both a Democratic/swing county and a state with less discriminatory laws, relative to a Republican county and a state with more discriminatory laws, was associated with a 10-percentage point increase in PrEP use (0.10; 0.06,0.14) and a 5-percentage point increase in HIV/STI testing (0.05; 0.00,0.09). CONCLUSION: More progressive state and local policies were each associated with increased PrEP use, and together, doubled the magnitude of this association. PrEP is underutilized among SGM youth, and anti-LGBTQ+ policies may exacerbate this gap in coverage.

Assessing the durability of a cash transfer on physical intimate partner violence and sexual relationships among adolescent girls and young women in rural South Africa.

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.

Trajectories of intimate partner violence and their relationship to stress among young women in South Africa: An HPTN 068 study.

BACKGROUND: One in four South African women will experience intimate partner violence (IPV) in their lifetime, potentially increasing their biological stress. In South Africa, limited IPV and stress research has utilized multiple timepoints or examined modifying factors. Cash transfers (CTs) are associated with reduced IPV and stress and may be an intervention target. AIMS: We used data-driven methods to identify longitudinal IPV trajectory groups among South African adolescent girls and young women (AGYW), estimate each group's association with stress, and assess modification by a CT. METHODS: A total of 2,183 South African AGYW ages 13 to 24 years from the HIV Prevention Trials Network 068 study were randomized to a CT or control group. Physical IPV was measured five times (2011-2017), and stress was captured once (2018-2019). Stress measures included the Cohen Stress Scale and stress biomarkers (C-reactive protein (CRP), cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1)). Group-based trajectory modeling identified IPV trajectories; ordinal logistic regression estimated the association between trajectory group and stress. RESULTS: A two-group quadratic trajectory model was identified (higher trajectory group = 26.7% of AGYW; lower trajectory group = 73.3%). In both groups, the probability of IPV increased from ages 13 to 17 years before declining in early adulthood. However, the higher group's probability peaked later and declined gradually. The higher trajectory group was associated with an increased odds of elevated CRP (OR: 1.41, 95% CI [1.11, 1.80]), but not with other stress measures. The CT modified the relationship with CMV: a positive association was observed among the usual care arm (OR: 1.59, 95% CI [1.11, 2.28]) but not the CT arm (OR: 0.85, 95% CI [0.61, 1.19]). CONCLUSIONS: Sustained IPV risk during adolescence was associated with elevated CRP in young adulthood. The relationship between IPV and elevated CMV was attenuated among those receiving a CT, suggesting that CTs could possibly reduce biological stress due to IPV.

The Acceptability, Feasibility, and Preliminary Effectiveness of a Courier HIV-Treatment Delivery and SMS Support Intervention for Young People Living With HIV in South Africa.

BACKGROUND: Young people living with HIV (YPLWH) experience poorer rates of virological suppression compared with adults. Differentiated service delivery models for YPLWH are urgently needed to address this disparity. SETTING: Participants were recruited from an HIV treatment clinic near Cape Town, South Africa. METHODS: We conducted a longitudinal pilot study to examine the acceptability, feasibility, and preliminary effectiveness of a courier ART delivery and SMS support intervention to retain YPLWH (13-24 years) in care during COVID-19. YPLWH had the option to enroll in the courier service and were randomized 1:1 to receive adherence support via a weekly SMS. Modified Poisson regression was used to estimate the preliminary effectiveness of the courier intervention on viral suppression (HIV-1 RNA <200 copies/mL) at months 3 and 6. RESULTS: Among 215 participants, 82% elected to enroll in the courier ART service at baseline, 41% reported receiving a delivery in the past 3 months at month 3, and 49% reported receiving a delivery in the past 3 months at month 6. Among those who received a delivery, most (91%-100%) rated the intervention as acceptable. Participants who reported receiving a delivery in the past 3 months at month 3 were 1.26 (95% CI: 1.05, 1.54) times as likely to have a suppressed viral load at month 3 and 1.21 (0.99, 1.48) times as likely at month 6, controlling for potential confounders. CONCLUSIONS: Findings reveal high uptake and acceptability of a courier ART delivery intervention among YPLWH and promising evidence for its effectiveness in increasing the probability of viral suppression. A fully powered trial is warranted.

Efficacy of Messenger RNA-1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021.

Background: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. Methods: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. Results: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. Conclusions: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. Clinical Trials Registration: NCT04811664.

Associations between psychosocial wellbeing and experience of gender-based violence at community, household, and intimate-partner levels among a cross-sectional cohort of young people living with and without HIV during COVID-19 in Cape Town, South Africa.

BACKGROUND: Growing evidence indicates that gender-based violence (GBV) increased during COVID-19. We investigated self-reported impact of the pandemic on GBV at community, household and intimate partner (IPV) levels among young people and its associations with psychosocial wellbeing, i.e., COVID-related stressors and mental health. METHODS: Cross-sectional data were drawn from a survey with young people ages 13-24 (N = 536) living with HIV (YPLWH) and without HIV (YPLWoH), in peri-urban Cape Town, South Africa. The survey, conducted February-October 2021, examined the impact of the initial lockdown on experience and perceived changes in GBV at each level, and pandemic-related psychosocial wellbeing. Descriptive statistics and binomial and multinomial regression analyses were conducted to illustrate exposure and perceived changes in GBV since lockdown, and their association with COVID-related stress factors (e.g., social isolation, anxiety about COVID), mental health (e.g., depression, anxiety), and other risk factors (e.g., age, gender, socioeconomic status) by HIV status. RESULTS: Participants were 70% women with mean age 19 years; 40% were living with HIV. Since lockdown, YPLWoH were significantly more likely than YPLWH to perceive community violence as increasing (45% vs. 28%, p < 0.001), and to report household violence (37% vs. 23%, p = 0.006) and perceive it as increasing (56% vs. 27%, p = 0.002) (ref: decreasing violence). YPLWoH were also more likely to report IPV experience (19% vs. 15%, p = 0.41) and perception of IPV increasing (15% vs. 8%, p = 0.92). In adjusted models, COVID-related stressors and common mental health disorders were only associated with household violence. However, indicators of economic status such as living in informal housing (RRR = 2.07; 95% CI = 1.12-3.83) and food insecurity (Community violence: RRR = 1.79; 95% CI = 1.00-3.20; Household violence: RRR = 1.72; 95% CI = 1.15-2.60) emerged as significant risk factors for exposure to increased GBV particularly among YPLWoH. CONCLUSIONS: Findings suggest that for young people in this setting, GBV at community and household levels was more prevalent during COVID-19 compared to IPV, especially for YPLWoH. While we found limited associations between COVID-related stressors and GBV, the perceived increases in GBV since lockdown in a setting where GBV is endemic, and the association of household violence with mental health, is a concern for future pandemic responses and should be longitudinally assessed.

Understanding the effects of universal test and treat on longitudinal HIV care outcomes among South African youth: a retrospective cohort study.

INTRODUCTION: Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority population in the UTT era. METHODS: Using medical record data, we conducted a retrospective cohort study among youth aged 18-24 diagnosed with HIV from August 2015-December 2018 in nine health care facilities in South Africa. We used Fine and Gray sub-distribution proportional hazards models to characterize longitudinal care continuum outcomes in the population overall and stratified by treatment era of diagnosis. We estimated the proportion of individuals in each stage of the continuum over time and the restricted mean time spent in each stage in the first year following diagnosis. Sub-group estimates were compared using differences. RESULTS: A total of 420 YLHIV were included. By day 365 following diagnosis, just 23% of individuals had no 90-or-more-day lapse in care and were virally suppressed. Those diagnosed in the UTT era spent less time as ART-naïve (mean difference=-19.3 days; 95% CI: -27.7, -10.9) and more time virally suppressed (mean difference = 17.7; 95% CI: 1.0, 34.4) compared to those diagnosed pre-UTT. Most individuals who were diagnosed in the UTT era and experienced a 90-or-more-day lapse in care disengaged between diagnosis and linkage to care or ART initiation and viral suppression. CONCLUSIONS: Implementation of UTT yielded modest improvements in time spent on ART and virally suppressed among South African YLHIV- however, meeting UNAIDS' 95-95-95 targets remains a challenge. Retention in care and re-engagement interventions that can be implemented between diagnosis and linkage to care and between ART initiation and viral suppression (e.g., longitudinal counseling) may be particularly important to improving care outcomes among South African YLHIV in the UTT era.

Intimate partner violence is associated with cytomegalovirus among young women in rural South Africa: An HPTN 068 analysis.

ABSTRACTStressful 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.

Oral SARS-CoV-2 host responses predict the early COVID-19 disease course.

Objectives: Oral fluids provide ready detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to determine relationships between oral virus, oral anti-SARS-CoV-2-specific antibodies, and symptoms. Methods: Saliva/throat wash (saliva/TW) were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+, subjects (n=47). SARS-CoV-2 RT-qPCR, N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR targeting viral subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. Statistical analyses were performed. Results: At baseline, LFA-detected N-antigen was immunoblot-confirmed in 82% of TW. However, only 3/17 were saliva/TW qPCR+. Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three negative subjects suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19-29aa, RMSD 1-1.5 Angstroms). At entry, symptomatic subjects demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (75%/63%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral IgG correlated 100% with NP+PCR status. Cough and fatigue severity (p=0.0008 and 0.016), and presence of nausea, weakness, and composite upper respiratory symptoms (p=0.005, 0.037 and 0.017) were negatively associated with oral IgM. Female oral IgM levels were higher than male (p=0.056). Conclusion: Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms, early Ig responses, and gender during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.

Clinic presentation delay and tuberculosis treatment outcomes in the Lake Victoria region of East Africa: A multi-site prospective cohort study.

In the Lake Victoria region of East Africa, little is known about delays between tuberculosis (TB) symptom onset and presentation at a clinic. Associations between clinic presentation delay and TB treatment outcomes are also poorly understood. In 2019, we abstracted data from routine TB treatment records for all adults (n = 776) initiating TB treatment in a 6-month period across 12 health facilities near Lake Victoria. We interviewed 301 cohort members and assessed whether they experienced a clinic presentation delay longer than 6 weeks. We investigated potential clinical and demographic correlates of clinic presentation delay and examined the association between clinic presentation delay and an unfavorable TB treatment outcome (death, loss to follow-up, or treatment failure). Clinic presentation delay was common, occurring among an estimated 54.7% (95% CI: 48.9%, 61.2%) of cohort members, though no specific correlates were identified. Clinic presentation delay was slightly associated with unfavorable TB treatment outcomes. The 180-day risk of an unfavorable outcome was 14.2% (95% CI: 8.0%, 20.4%) among those with clinic presentation delay, compared to 12.7% (95% CI: 5.1%, 20.3%) among those presenting earlier. Multi-level community-based interventions may be necessary to reduce clinic presentation delays in communities near Lake Victoria.

Oral SARS-CoV-2 host responses predict the early COVID-19 disease course.

Objectives: Oral fluids provide ready detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to determine relationships between oral virus, oral anti-SARS-CoV-2-specific antibodies, and symptoms. Methods: Saliva/throat wash (saliva/TW) were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+, subjects (n=47). SARS-CoV-2 RT-qPCR, N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR targeting viral subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. Statistical analyses were performed. Results: At baseline, LFA-detected N-antigen was immunoblot-confirmed in 82% of TW. However, only 3/17 were saliva/TW qPCR+. Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three negative subjects suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19-29aa, RMSD 1-1.5 Angstroms). At entry, symptomatic subjects demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (75%/63%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral IgG correlated 100% with NP+PCR status. Cough and fatigue severity (p=0.0008 and 0.016), and presence of nausea, weakness, and composite upper respiratory symptoms (p=0.005, 0.037 and 0.017) were negatively associated with oral IgM. Female oral IgM levels were higher than male (p=0.056). Conclusion: Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms, early Ig responses, and gender during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.