Preliminary Impact of Group-Based Interventions on Stigma, Mental Health, and Treatment Adherence Among Adolescents Living with Human Immunodeficiency Virus in Uganda.

OBJECTIVE: To examine the preliminary impact of group cognitive behavioral therapy and multiple family group-based family strengthening to address HIV stigma and improve the mental health functioning of adolescents living with HIV in Uganda. STUDY DESIGN: We analyzed data from the Suubi4Stigma study, a 2-year pilot randomized clinical trial that recruited adolescents living with HIV (10-14 years) and their caregivers (n = 89 dyads), from 9 health clinics. We fitted separate three-level mixed-effects linear regression models to test the effect of the interventions on adolescent outcomes at 3 and 6 months post intervention initiation. RESULTS: The average age was 12.2 years and 56% of participants were females. Participants in the multiple family group-based family strengthening intervention reported lower levels of internalized stigma (mean difference = -0.008, 95% CI = -0.015, -0.001, P = .025) and depressive symptoms at 3 months (mean difference = -0.34, 95% CI = -0.53, -0.14, P < .001), compared with usual care. On the other hand, participants in the group cognitive behavioral therapy intervention reported lower levels of anticipated stigma at 3 months (mean difference = -0.039, 95% CI = -0.072, -0.006), P = .013) and improved self-concept at 6 months follow-up (mean difference = 0.04, 95% CI = 0.01, 0.01, P = .025). CONCLUSION: Outcome trends from this pilot study provide compelling evidence to support testing the efficacy of these group-based interventions on a larger scale. TRIAL REGISTRATION: The study is registered in the Clinical trials.gov database (Identifier #: NCT04528732).

A positive affect intervention alters leukocyte DNA methylation in sexual minority men with HIV who use methamphetamine.

OBJECTIVE: This epigenomics sub-study embedded within a randomized controlled trial examined whether an evidenced-based behavioral intervention model that decreased stimulant use altered leukocyte DNA methylation (DNAm). METHODS: Sexual minority men with HIV who use methamphetamine were randomized to a five-session positive affect intervention (n = 32) or an attention-control condition (n = 21), both delivered during three months of contingency management for stimulant abstinence. All participants exhibited sustained HIV virologic control - an HIV viral load less than 40 copies/mL at baseline and six months post-randomization. The Illumina EPIC BeadChip measured leukocyte methylation of cytosine-phosphate-guanosine (CpG) sites mapping onto five a priori candidate genes of interest (i.e., ADRB2, BDNF, FKBP5, NR3C1, OXTR). Functional DNAm pathways and soluble markers of immune dysfunction were secondary outcomes. RESULTS: Compared to the attention-control condition, the positive affect intervention significantly decreased methylation of CpG sites on genes that regulate ß2 adrenergic and oxytocin receptors. There was an inconsistent pattern for the direction of the intervention effects on methylation of CpG sites on genes for glucocorticoid receptors and brain-derived neurotrophic factor. Pathway analyses adjusting for the false discovery rate (padj < 0.05) revealed significant intervention-related alterations in DNAm of Reactome pathways corresponding to neural function as well as dopamine, glutamate, and serotonin release. Positive affect intervention effects on DNAm were accompanied by significant reductions in the self-reported frequency of stimulant use. CONCLUSIONS: There is an epigenetic signature of an evidence-based behavioral intervention model that reduced stimulant use, which will guide the identification of biomarkers for treatment responses.

Pilot Trial Results of Mlambe: An Economic and Relationship-Strengthening Intervention to Address Heavy Drinking and Adherence to Antiretroviral Therapy in Malawi.

We evaluated the feasibility, acceptability, and preliminary efficacy of an economic and relationship-strengthening intervention to reduce heavy alcohol use among couples living with HIV in Malawi (Mlambe). Mlambe consisted of training on financial literacy and relationship skills, combined with 1:1 matched savings accounts to invest in an income-generating activity. In a randomized controlled trial, we compared Mlambe to enhanced usual care (EUC). We enrolled 78 married couples having a partner on antiretroviral therapy (ART) who reported heavy alcohol use based on the AUDIT-C. Using targets of 75%, primary outcomes included retention rates at 10 and 15-months, session attendance rates, and satisfaction with Mlambe. Exploratory outcomes were heavy alcohol use (AUDIT-C and/or PEth positive), number of drinking days in the past month, AUDIT-C score, optimal adherence to ART (95% or higher), and viral suppression. We exceeded our targets for feasibility and acceptability metrics. Retention rates were 96% at 15-months. Session attendance and satisfaction levels were both 100%. From baseline to 15-months, Mlambe participants reported decreases in mean number of drinking days (from 6.8 to 2.1) and AUDIT-C scores (from 7.5 to 3.1); while ART adherence rates improved across the same period (from 63.2 to 73.9%). Participants in Mlambe, as compared to those in EUC, had lower rates of heavy alcohol use (89.5% vs. 97.2%) and higher rates of viral suppression (100% vs. 91.9%) at 10-months. Differences between arms were not statistically significant in this small pilot study. Mlambe was highly feasible and acceptable, and shows promise for reducing heavy alcohol use and viral non-suppression among couples with HIV in a larger efficacy study.

Intersectional Stigma, Fear of Negative Evaluation, Depression, and ART Adherence Among Women Living with HIV Who Engage in Substance Use: A Latent Class Serial Mediation Analysis.

Women Living with HIV (WLHIV) who use substances face stigma related to HIV and substance use (SU). The relationship between the intersection of these stigmas and adherence to antiretroviral therapy (ART), as well as the underlying mechanisms, remains poorly understood. This study aimed to examine the association between intersectional HIV and SU stigma and ART adherence, while also exploring the potential role of depression and fear of negative evaluation (FNE) by other people in explaining this association. We analyzed data from 409 WLHIV collected between April 2016 and April 2017, Using Multidimensional Latent Class Item Response Theory analysis. We identified five subgroups (i.e., latent classes [C]) of WLHIV with different combinations of experienced SU and HIV stigma levels: (C1) low HIV and SU stigma; (C2) moderate SU stigma; (C3) higher HIV and lower SU stigma; (C4) moderate HIV and high SU stigma; and (C5) high HIV and moderate SU stigma. Medication adherence differed significantly among these classes. Women in the class with moderate HIV and high SU stigma had lower adherence than other classes. A serial mediation analysis suggested that FNE and depression symptoms are mechanisms that contribute to explaining the differences in ART adherence among WLHIV who experience different combinations of intersectional HIV and SU stigma. We suggest that FNE is a key intervention target to attenuate the effect of intersectional stigma on depression symptoms and ART adherence, and ultimately improve health outcomes among WLHIV.

Barriers to accessing care for cardiometabolic disorders in Malawi: partners as a source of resilience for people living with HIV.

BACKGROUND: People living with HIV (PLWH) are at increased risk of cardiometabolic disorders (CMD). Adequate access to care for both HIV and CMD is crucial to improving health outcomes; however, there is limited research that have examined couples' experiences accessing such care in resource-constrained settings. We aimed to identify barriers to accessing CMD care among PLWH in Malawi and the role of partners in mitigating these barriers. METHODS: We conducted a qualitative investigation of barriers to CMD care among 25 couples in Malawi. Couples were eligible if at least one partner was living with HIV and had hypertension or diabetes (i.e., the index patient). Index patients were recruited from HIV care clinics in the Zomba district, and their partners were enrolled thereafter. Interviews were conducted separately with both partners to determine barriers to CMD care access and how partners were involved in care. RESULTS: Participants framed their experiences with CMD care by making comparisons to HIV treatment, which was free and consistently available. The main barriers to accessing CMD care included shortage of medications, cost of tests and treatments, high cost of transportation to health facilities, lengthy wait times at health facilities, faulty or unavailable medical equipment and supplies, inadequate monitoring of patients' health conditions, some cultural beliefs about causes of illness, use of herbal therapies as an alternative to prescribed medicine, and inadequate knowledge about CMD treatments. Partners provided support through decision-making on accessing medical care, assisting partners in navigating the healthcare system, and providing financial assistance with transportation and treatment expenses. Partners also helped manage care for CMD, including communicating health information to their partners, providing appointment reminders, supporting medication adherence, and supporting recommended lifestyle behaviors. CONCLUSIONS: Couples identified many barriers to CMD care access, which were perceived as greater challenges than HIV care. Partners provided critical forms of support in navigating these barriers. With the rise of CMD among PLWH, improving access to CMD care should be prioritized, using lessons learned from HIV and integrated care approaches. Partner involvement in CMD care may help mitigate most barriers to CMD care.

Correlation between gender-based violence and poor treatment outcomes among transgender women living with HIV in Brazil.

BACKGROUND: Transgender women are disproportionately affected by both HIV and gender-based violence (GBV), defined as physical, sexual, or emotional violence perpetrated against an individual based on their gender identity/expression. While a growing body of evidence demonstrates that GBV leads to poor HIV care and treatment outcomes among cisgender women, less research has examined this association among transgender women. We assessed the impact of lifetime experiences of GBV on subsequent retention in HIV care and laboratory confirmed viral suppression among a sample of transgender women living with HIV (TWH) in Brazil. METHODS: A pilot trial of a peer navigation intervention to improve HIV care and treatment among TWH was conducted in São Paulo, Brazil between 2018 and 2019. TWH were recruited and randomized into the intervention or control arm and participated in a baseline and 9-month follow-up survey and ongoing extraction of clinical visit, prescribing, and laboratory data. Generalized linear model regressions with a Poisson distribution estimated the relative risk (RR) for the association of lifetime physical and sexual violence reported at baseline with treatment outcomes (retention in HIV care and viral suppression) at follow-up, adjusting for baseline sociodemographic characteristics. RESULTS: A total of 113 TWH participated in the study. At baseline, median age was 30 years, and the prevalence of lifetime physical and sexual violence was 62% and 45%, respectively. At follow-up, 58% (n = 66/113) were retained in care and 35% (n = 40/113) had evidence of viral suppression. In adjusted models, lifetime physical violence was non-significantly associated with a 10% reduction in retention in care (aRR: 0.90, 95% CI: 0.67, 1.22) and a 31% reduction in viral suppression (aRR: 0.69; 95% CI: 0.43, 1.11). Lifetime sexual violence was non-significantly associated with a 28% reduction in retention in HIV care (aRR: 0.72, 95% CI: 0.52, 1.00) and significantly associated with a 56% reduction in viral suppression (aRR: 0.44; 95% CI: 0.24, 0.79). CONCLUSION: Our findings are among the first to demonstrate that lifetime experiences with physical and sexual violence are associated with poor HIV outcomes over time among transgender women. Interventions seeking to improve HIV treatment outcomes should assess and address experiences of GBV among this population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03525340.

The Brief Human Immunodeficiency Virus (HIV) Index: A Rapid 3-Item Scale to Measure Engagement in HIV Care.

We created a brief version of The Index, a validated patient-reported measure that has potential to quickly identify patients at risk for poor retention. We analyzed Index scores from 2406 patients from 2016 to 2017 in a national cohort of patients in human immunodeficiency virus (HIV) care. Index scores predicted poor retention 12 months after administered.

Early life adversity predicts an accelerated cellular aging phenotype through early timing of puberty.

BACKGROUND: The current study examined if early adversity was associated with accelerated biological aging, and if effects were mediated by the timing of puberty. METHODS: In early mid-life, 187 Black and 198 White (Mage = 39.4, s.d.age = 1.2) women reported on early abuse and age at first menstruation (menarche). Women provided saliva and blood to assess epigenetic aging, telomere length, and C-reactive protein. Using structural equation modeling, we created a latent variable of biological aging using epigenetic aging, telomere length, and C-reactive protein as indicators, and a latent variable of early abuse using indicators of abuse/threat events before age 13, physical abuse, and sexual abuse. We estimated the indirect effects of early abuse and of race on accelerated aging through age at menarche. Race was used as a proxy for adversity in the form of systemic racism. RESULTS: There was an indirect effect of early adversity on accelerated aging through age at menarche (b = 0.19, 95% CI 0.03-0.44), in that women who experienced more adversity were younger at menarche, which was associated with greater accelerated aging. There was also an indirect effect of race on accelerated aging through age at menarche (b = 0.25, 95% CI 0.04-0.52), in that Black women were younger at menarche, which led to greater accelerated aging. CONCLUSIONS: Early abuse and being Black in the USA may both induce a phenotype of accelerated aging. Early adversity may begin to accelerate aging during childhood, in the form of early pubertal timing.

Economic Empowerment, HIV Risk Behavior, and Mental Health Among School-Going Adolescent Girls in Uganda: Longitudinal Cluster-Randomized Controlled Trial, 2017‒2022.

Objectives. To investigate the long-term (12- and 24-month) impact of an economic empowerment intervention on HIV risk behaviors and mental health among school-going adolescent girls in Uganda. Methods. A total of 1260 girls aged 14 to 17 years were randomized at the school level to (1) standard health and sex education (controls; n = 408 students; n = 16 schools), (2) 1-to-1 matched savings youth development account (YDA; n = 471 students; n = 16 schools), or (3) combination intervention (YDA and multiple family group [YDA+MFG]; n = 15 schools; n = 381 students). Mixed-effects models were fitted. Results. YDA and YDA+MFG girls had significantly lower depressive symptoms and better self-concept than controls at 24 months. Only YDA+MFG girls had significantly lower hopelessness levels than controls. There were no significant study group differences at 12 and 24 months for sexual risk-taking behavior and attitudes. There was no significant difference between YDA and YDA+MFG groups for all outcomes. Conclusions. Providing YDA and MFG can positively improve adolescent girls' mental health, but our analyses showed no significant differences across groups on sexual risk-taking behaviors. Future studies may consider replicating these interventions and analyses in older populations, including those transitioning into young adults. Trial Registration. ClinicalTrials.gov Identifier: NCT03307226. (Am J Public Health. 2023;113(3):306-315. https://doi.org/10.2105/10.2105/AJPH.2022.307169).

Development of an Economic and Relationship-Strengthening Intervention for Alcohol Drinkers Living with HIV in Malawi.

Heavy alcohol use among people with HIV in sub-Saharan Africa is driven by household economics such as poverty and unemployment and has negative impacts on couple relationships. Multilevel interventions have the potential to reduce alcohol use and improve relationship outcomes by addressing the web of co-occurring economic, social, and dyadic factors. This objective of this study was to develop an economic and relationship-strengthening intervention for couples in Malawi, consisting of matched savings accounts with financial literacy training and a couples counseling component to build relationship skills. Informed by the ADAPT-ITT framework, we collected multiple rounds of focus group data with key stakeholders and couples to gain input on the concept, session content, and procedures, held team meetings with field staff and an international team of researchers to tailor the intervention to couples in Malawi, and refined the intervention manual and components. The results describe a rigorous adaptation process based on the eight steps of ADAPT-ITT, insights gained from formative data and modifications made, and a description of the final intervention to be evaluated in a pilot randomized clinical trial. The economic and relationship-strengthening intervention shows great promise of being feasible, acceptable, and efficacious for couples affected by HIV and heavy alcohol use in Malawi.

Socio-ecological Barriers to Viral Suppression Among Transgender Women Living with HIV in San Francisco and Los Angeles, California.

Troubling disparities in viral suppression persist among transgender (trans) women living with HIV in the US. We utilized baseline data from a randomized controlled trial of a behavioral intervention among trans women living with HIV in San Francisco and Los Angeles, to identify the socio-ecological correlates of biologically confirmed viral suppression (< 200 HIV-1 RNA copies/mL). Among 253 participants, the mean age was 43 (SD = 11), 46% identified as Black or African American and 35% were virally non-suppressed. In adjusted Poisson regression models, the following barriers to viral suppression were identified: injection drug use [adjusted risk ratio (aRR) 0.78, 95% CI 0.65-0.93, Z = - 2.64, p = 0.008], methamphetamine use (aRR 0.65, 95% CI 0.51-0.83, Z = - 3.45, p = 0.001), amphetamine use (aRR 0.62, 95% CI 0.44-0.87, Z = - 2.75, p = 0.006), homelessness (aRR 0.79, 95% CI 0.63-0.98, Z = - 2.06, p = 0.039), and sex work (aRR 0.60, 95% CI 0.41-0.86, Z = - 2.77, p = 0.009). These findings underscore the importance of interventions that address the socio-ecological barriers to viral suppression among trans women in urban settings.

RESUMEN: Persisten disparidades preocupantes en la supresión viral entre las mujeres transgénero (trans) que viven con el VIH en los EE. UU. Utilizamos datos de referencia de un ensayo controlado aleatorizado de una intervención conductual entre mujeres trans que viven con el VIH en San Francisco y Los Ángeles, para identificar los correlatos socioecológicos de la supresión viral confirmada biológicamente (< 200 copias/ml de ARN del VIH-1). Entre 253 participantes, la edad media fue de 43 años (DE = 11), el 46% se identificó como negro o afroamericano y el 35% no tenía supresión viral. En modelos de regresión de Poisson ajustados, se identificaron las siguientes barreras para la supresión viral: uso de drogas inyectables [razón de riesgo ajustada (aRR) 0,78, IC del 95% 0,65­0,93, Z = − 2,64, p = 0,008], uso de metanfetamina (aRR 0,65, IC 95% 0,51­0,83, Z = − 3,45, p = 0,001), consumo de anfetaminas (aRR 0,62, IC 95% 0,44­0,87, Z = − 2,75, p = 0,006), falta de vivienda (aRR 0,79, IC 95% 0,63­0,98, Z = − 2,06, p = 0,039), y trabajo sexual (aRR 0,60, IC 95% 0,41­0,86, Z = − 2,77, p = 0,009). Estos hallazgos subrayan la importancia de las intervenciones que abordan las barreras socioecológicas para la supresión viral entre las mujeres trans en entornos urbanos.

The Impact of an Economic Strengthening Intervention on Academic Achievement Among Adolescents Living with HIV: Findings from the Suubi + Adherence Cluster-Randomized Trial in Uganda (2012-2018).

We examined the impact of a family-based economic strengthening intervention on school dropout and repeating a class among ALWHIV in Uganda. In this cluster-randomized trial (2012-2018) conducted in 39 clinics, we recruited adolescents aged 10-16 years living with HIV. We included data from 613 adolescents. We plotted a Kaplan Meier survival curve and fitted Cox proportional hazards models to test the effect of the economic strengthening intervention on school dropout. The incidence of school dropout was 13.0% and 9.6% in the control and intervention groups, respectively. Also, economic empowerment reduced the risk of school dropout, aHR = 0.68 (95% CI 0.52-0.88), p-value 0.004. In other words, participants in the intervention group had 32% reduced hazards of dropping out of school. Also, increasing age aHR = 1.54 (95% CI 1.42-1.66), p-value < 0.001 and double orphanhood aHR = 0.67 (95% CI 0.47-0.96) p-value 0.030 increased the risks for dropping out of school. The intervention was not efficacious in reducing the rates of repeating a class. The intervention offered the ALWHIV an opportunity to live a productive adult life. More research is required on these kinds of interventions intended to keep ALWHIV and those impacted by HIV in school.

Mobility is Associated with Higher-risk Sexual Partnerships Among Both Men and Women in Co-resident Couples in Rural Kenya and Uganda: A Longitudinal Cohort Study.

Population mobility is associated with higher-risk sexual behaviors in sub-Saharan Africa and is a key driver of the HIV epidemic. We conducted a longitudinal cohort study to estimate associations between recent mobility (overnight travel away from home in past six months) or migration (changes of residence over defined geopolitical boundaries) and higher-risk sexual behavior among co-resident couples (240 couples aged ≥ 16) from 12 rural communities in Kenya and Uganda. Data on concurrent mobility and sexual risk behaviors were collected every 6-months between 2015 and 2020. We used sex-pooled and sex-stratified multilevel models to estimate associations between couple mobility configurations (neither partner mobile, male mobile/female not mobile, female mobile/male not mobile, both mobile) and the odds of higher-risk (casual, commercial sex worker/client, one night stand, inherited partner, stranger) and concurrent sexual partnerships based on who was mobile. On average across all time points and subjects, mobile women were more likely than non-mobile women to have a higher-risk partner; similarly, mobile men were more likely than non-mobile men to report a higher-risk partnership. Men with work-related mobility versus not had higher odds of higher-risk partnerships. Women with work-related mobility versus not had higher odds of higher-risk partnerships. Couples where both members were mobile versus neither had greater odds of higher-risk partnerships. In analyses using 6-month lagged versions of key predictors, migration events of men, but not women, preceded higher-risk partnerships. Findings demonstrate HIV risks for men and women associated with mobility and the need for prevention approaches attentive to the risk-enhancing contexts of mobility.

Young Adult Responses to Peer Crowd-Based Targeting in E-cigarette Advertisements: An Experimental Study.

AIMS: To examine the effects of psychographically targeted e-cigarette advertisements on young adults. METHODS: A total of 2100 young adults (18-29 years old) representing five peer crowds (groups with shared values, interests, and lifestyle: Mainstream, Young Professional, Hip Hop, Hipster, and Partier) were recruited from a nationwide opt-in online panel. Participants were randomly assigned to view e-cigarette advertisements featuring characters that either did or did not match their own peer crowd affiliation and evaluated advertising effectiveness using Likert-type and semantic differential scales. Participants also reported their attitudes toward using e-cigarettes. RESULTS: No significant overall effect of peer crowd matching was observed. However, significant two-way interaction effects emerged where matching advertisements yielded higher evaluations than mismatching advertisements among those who currently do not use tobacco and nicotine products and among Mainstream participants. Advertisements featuring Mainstream characters were in general rated more highly than other advertisements. Additional analyses found significant effects of peer crowd matching among those who viewed advertisements featuring non-Mainstream characters. CONCLUSIONS: Peer crowd-based targeting can increase the effectiveness of e-cigarette advertisements which may impact initiation among current nonusers, requiring stricter marketing regulations. More research is needed to determine if anti-tobacco messaging tailored by peer crowds may effectively counteract targeted e-cigarette marketing. IMPLICATIONS: E-cigarette advertisements often use psychographic targeting strategies, using lifestyles, attitudes, and values. Low-risk young adults (eg, those who currently do not use tobacco and nicotine products) are susceptible to psychographically targeted e-cigarette advertisements. This may result in the initiation of e-cigarette use among young adults who would otherwise be less likely to use tobacco and nicotine products. Stricter marketing regulations for emerging tobacco and nicotine products are required to reduce marketing exposure.

Resilience and Its Limits: The Roles of Individual Resilience, Social Capital, Racial Discrimination, and Binge Drinking on Sexual Behavior Among Black Heterosexual Men.

In response to the increased recognition of racism as a public health crisis, we assessed links between racial discrimination and HIV-related risk behavior for Black men. Specifically, using survey data from 530 Black heterosexual men (18-44 years old, M = 31.0, SD = 7.8), we tested two moderated-mediation models: (1) a protective model, in which resilience and social capital protected against the indirect effect of racial discrimination on alcohol-related sexual behavior via binge drinking, and (2) a bounded model, in which racial discrimination limited the indirect effects of resilience and social capital on alcohol-related sexual behavior via binge drinking. We found support for the bounded model only. Specifically, resilience was indirectly associated with decreased alcohol-related sexual behavior via lower binge drinking when racial discrimination was low to moderately high, but not when racial discrimination was at its highest levels. Resilience was not directly associated with alcohol-related sexual behavior. Social capital was directly related to lower odds of alcohol-related sexual behavior. At high levels of racial discrimination, however, social capital was indirectly related to increased alcohol-related sexual behavior via binge drinking. High levels of racial discrimination limit beneficial effects of resilience on alcohol-related sexual behavior. Social capital maintains a beneficial effect if social bonds are not associated with binge-drinking norms or behaviors. Results highlight the limitations of individual-level resilience and the need to conceptualize and support resilience as a social-structural resource.

Supportive couple relationships buffer against the harms of HIV stigma on HIV treatment adherence.

INTRODUCTION: HIV stigma can impact couple relationships through stress or bring partners closer through shared experiences. Conversely, couple relationships may protect against the harms of stigma, including anticipated stigma on negative health outcomes. Yet few studies have assessed the potential link between HIV stigma, relationship dynamics, and antiretroviral therapy (ART) adherence. Using dyadic data from a cross-sectional study of Malawian couples living with HIV, we tested associations between anticipated stigma and: 1) relationship dynamics (e.g., trust, sexual satisfaction, communication) and partner support; and 2) self-reported ART adherence. METHODS: Heterosexual couples (211 couples, 422 individuals) with at least one partner on ART were recruited from clinics in Zomba, Malawi. Partners completed separate surveys on anticipated stigma, relationship dynamics, and ART adherence. Linear mixed models evaluated associations between anticipated stigma and relationship dynamics, and whether associations varied by gender. Generalized estimating equation models tested for associations between anticipated stigma and high ART adherence (90-100% vs. < 90%) at the individual level, and whether they were moderated by relationship dynamics at the couple level. RESULTS: Couples' relationship length averaged 12.5 years, 66.8% were HIV sero-concordant, and 95.6% reported high ART adherence. In multivariable models, sexual satisfaction (ß = -0.22, 95%CI = -0.41;-0.03, p = 0.020) and partner social support (ß = -0.02, 95%CI = -0.04;-0.01, p < 0.01) were negatively associated with anticipated stigma. Significant interaction effects showed that adherence is moderated in couples with higher partner support and sexual satisfaction such that adherence is lowest when anticipated stigma is high and social support is low, and that adherence is lowest when anticipated stigma is high and sexual satisfaction is low. CONCLUSIONS: Increased anticipated stigma is most associated with lower ART non-adherence at lower levels of social support and sexual satisfaction. Conversely, supportive and fulfilling relationships may buffer the negative association between stigma and ART adherence. Couples' interventions that focus on improving communication and support systems within couples could reduce the negative impacts of anticipated stigma on couples living with HIV.

Suubi + Adherence4Youth: a study protocol to optimize the Suubi Intervention for Adherence to HIV treatment for youth living with HIV in Uganda.

BACKGROUND: Suubi is an evidenced based multi-component intervention that targets psychosocial and economic hardships to improve ART adherence, viral suppression, mental health, family financial stability, and family cohesion for adolescents living with HIV (ALHIV) in Uganda. Suubi was originally tested as a combined package of four components: 1) Financial Literacy Training; 2) incentivized matched Youth Savings Accounts with income-generating activities; 3) a manualized and visual-based intervention for ART adherence and stigma reduction; and 4) engagement with HIV treatment-experienced role models. However, it is unknown if each component in Suubi had a positive effect, how the components interacted, or if fewer components could have produced equivalent effects. Hence, the overall goal of this new study is to identify the most impactful and sustainable economic and psychosocial components across 48 health clinics in Uganda. METHODS: A total of 576 ALHIV (aged 11-17 years at enrollment) will be recruited from 48 clinics and each clinic will be randomized to one of 16 study conditions. Each condition represents every possible combination of the 4 components noted above. Assessments will be conducted at baseline, 12, 24, 36 and 48- months post-intervention initiation. Using the multi-phase optimization strategy (MOST), we will identify the optimal combination of components and associated costs for viral suppression, as well as test key mediators and moderators of the component-viral suppression relationship. DISCUSSION: The study is a shift in the paradigm of research to use new thinking to build/un-pack highly efficacious interventions that lead to new scientific knowledge in terms of understanding what drives an intervention's success and how to iterate on them in ways that are more efficient, affordable and scalable. The study advances intervention science for HIV care outcomes globally. TRIAL REGISTRATION: This project was registered at clinicaltrials.gov (NCT05600621) on October, 31, 2022. https://clinicaltrials.gov/ct2/show/NCT05600621.

A factorial experiment grounded in the multiphase optimization strategy to promote viral suppression among people who inject drugs on the Texas-Mexico border: a study protocol.

BACKGROUND: People who inject drugs living with HIV (PWIDLH) suffer the lowest rates of HIV viral suppression due to episodic injection drug use and poor mental health coupled with poor retention in HIV care. Approximately 44% of PWIDLH along the US-Mexico border are retained in care and only 24% are virally suppressed. This underserved region faces a potential explosion of transmission of HIV due to highly prevalent injection drug use. This protocol describes an optimization trial to promote sustained viral suppression among Spanish-speaking Latinx PWIDLH. METHODS: The multiphase optimization strategy (MOST) is an engineering-inspired framework for designing and building optimized interventions and guides this intervention. The primary aim is to conduct a 24 factorial experiment in which participants are randomized to one of 16 intervention conditions, with each condition comprising a different combination of four behavioral intervention components. The components are peer support for methadone uptake and persistence; behavioral activation therapy for depression; Life-Steps medication adherence counseling; and patient navigation for HIV care. Participants will complete a baseline survey, undergo intervention, and then return for 3-,6-,9-, and 12-month follow-up assessments. The primary outcome is sustained viral suppression, defined as viral loads of < 40 copies per mL at 6-,9-, and 12-month follow-up assessments. Results will yield effect sizes for each component and each additive and interactive combination of components. The research team and partners will make decisions about what constitutes the optimized multi-component intervention by judging the observed effect sizes, interactions, and statistical significance against real-world implementation constraints. The secondary aims are to test mediators and moderators of the component-to-outcome relationship at the 6-month follow-up assessment. DISCUSSION: We are testing well-studied and available intervention components to support PWIDLH to reduce drug use and improve their mental health and engagement in HIV care. The intervention design will allow for a better understanding of how these components work in combination and can be optimized for the setting. TRIAL REGISTRATION: This project was registered at clinicaltrials.gov (NCT05377463) on May 17th, 2022.

HIV-related drivers of sexual compulsivity and sexuality in sexual minority men who use methamphetamine.

Although co-occurring methamphetamine (meth) use and HIV amplify the risk for neuropsychiatric comorbidities, the underlying neuroimmune mechanisms are not well characterized. We examined whether a detectable viral load and dysregulated metabolism of amino acid precursors for neurotransmitters predicted subsequent levels of sexual compulsivity and sexual sensation seeking. This 15-month longitudinal study enrolled 110 sexual minority men (SMM) living with HIV who had biologically confirmed meth use (i.e., reactive urine or hair toxicology results). Peripheral venous blood samples collected at baseline, 6 months, 12 months, and 15 months were used to measure a detectable viral load (> 40 copies/mL), the kynurenine/tryptophan (K/T) ratio, and the phenylalanine/tyrosine (P/T) ratio. The K/T and P/T ratios index dysregulated serotonin and catecholamine (e.g., dopamine) synthesis, respectively. In a cross-lagged panel model, a detectable viral load at 6 months predicted greater sexual compulsivity at 12 months after adjusting for prior levels of sexual compulsivity and recent stimulant use (ß = 0.26, p = 0.046). A greater P/T ratio at baseline predicted decreased sexual sensation seeking at 6 months (ß = - 0.25, p = 0.004) after adjusting for baseline sexual sensation seeking and recent stimulant use. Taken together, HIV replication and dysregulated catecholamine synthesis could potentiate sexual compulsivity while decreasing sexual pleasure in SMM who use meth.

The longitudinal impact of an evidence-based multiple family group intervention (Amaka Amasanyufu) on oppositional defiant disorder and impaired functioning among children in Uganda: analysis of a cluster randomized trial from the SMART Africa-Uganda scale-up study (2016-2022).

BACKGROUND: Oppositional Defiant Disorders (ODDs) and other Disruptive Behavior Disorders (DBDs) are common among children and adolescents in poverty-impacted communities in sub-Saharan Africa. Without early intervention, its progression into adulthood can result in dire consequences. We examined the impact of a manualized family strengthening intervention called Amaka Amasanyufu designed to reduce ODDs and other DBDs among school-going children residing in low-resource communities in Uganda. METHODS: We used longitudinal data from the SMART Africa-Uganda study (2016-2022). Public primary schools were randomized to: (1) Control condition (receiving usual care comprising generalized psychosocial functioning literature), 10 schools; (2) intervention delivered via parent peers (Amaka-parents), 8 schools or; (3) intervention delivered via community healthcare workers (Amaka-community), 8 schools. All the participants were blinded. At baseline, 8- and 16-weeks postintervention initiation, caregivers completed the Iowa Conners Scale, which measured Oppositional Defiant Disorder (ODD) and Impairment Rating Scale to evaluate children's overall impairment and impaired functioning with peers, siblings, and parents; impaired academic progress, self-esteem, and family functioning. Three-level linear mixed-effects models were fitted to each outcome. Pairwise comparisons of postbaseline group means within each time point were performed using Sidak's adjustment for multiple comparisons. Only children positive for ODD and other DBDs were analyzed. RESULTS: Six hundred and thirty-six children screened positive for ODDs and other DBDs (Controls: n = 243; Amaka-parents: n = 194; Amaka-community: n = 199). At 8 weeks, Amaka-parents' children had significantly lower mean scores for overall impairment compared to controls, (mean difference: -0.71, p = .001), while Amaka-community children performed better on ODD (mean difference: -0.84, p = .016). At 16 weeks, children in both groups were performing better on ODD and IRS than controls, and there were no significant differences between the two intervention groups. CONCLUSIONS: The Amaka Amasanyufu intervention was efficacious in reducing ODD and impaired functioning relative to usual care. Hence, the Amaka Amasanyufu intervention delivered either by Amaka-community or Amaka-parents has the potential to reduce negative behavioral health outcomes among young people in resource-limited settings and improve family functioning. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03081195. Registered on 16 March 2017.