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Abstract Triple negative breast cancer (TNBC) subtype is characterized with higher EMT/stemness properties and immune suppressive tumor microenvironment (TME). Women with advanced TNBC exhibit aggressive disease and have limited treatment options. Although immune suppressive TME is implicated in driving aggressive properties of basal/TNBC subtype and therapy resistance, effectively targeting it remains a challenge. Minnelide, a prodrug of triptolide currently being tested in clinical trials, has shown anti-tumorigenic activity in multiple malignancies via targeting super enhancers, Myc and anti-apoptotic pathways such as HSP70. Distinct super-enhancer landscape drives cancer stem cells (CSC) in TNBC subtype while inducing immune suppressive TME. We show that Minnelide selectively targets CSCs in human and murine TNBC cell lines compared to cell lines of luminal subtype by targeting Myc and HSP70. Minnelide in combination with cyclophosphamide significantly reduces the tumor growth and eliminates metastasis by reprogramming the tumor microenvironment and enhancing cytotoxic T cell infiltration in 4T1 tumor-bearing mice. Resection of residual tumors following the combination treatment leads to complete eradication of disseminated tumor cells as all mice are free of local and distant recurrences. All control mice showed recurrences within 3 weeks of post-resection while single Minnelide treatment delayed recurrence and one mouse was free of tumor. We provide evidence that Minnelide targets tumor intrinsic pathways and reprograms the immune suppressive microenvironment. Our studies also suggest that Minnelide in combination with cyclophosphamide may lead to durable responses in patients with basal/TNBC subtype warranting its clinical investigation.

Residing in poverty-impacted Ugandan communities and raising children with disruptive behavior disorders (DBDs) is associated with above heightened parenting stress. An evidence-based intervention designed to help parents tailor their parenting style to effectively manage children with DBDs was implemented in Uganda between 2017 and 2023. At the end of the intervention, caregivers displayed lower levels of parenting stress than controls, however the mechanisms by which stress reduction occurred is unknown. We investigated whether the intervention's effect on parenting stress was mediated by parenting practices, family cohesion, or mental health.Mediation was assessed using Mitchell and Maxwell's cross-lagged auto-regressive approach. Each mediation model regressed the outcome parenting stress score at each time point onto intervention group assignment (0 = Control; 1 = Multiple Family Group (MFG) intervention) and parenting stress score at the preceding time point. Each mediator was investigated one at a time and regressed onto intervention group assignment and the mediator score at the preceding time point. Parenting stress score was also regressed onto the preceding time point mediator score. The residuals for mediators and parenting stress were allowed to correlate at each time point. We included regression pathways from each covariate to the mediators and outcomes at subsequent waves and were included in the model as random variables.The findings show that the intervention had a significant direct effect on parenting stress at 16 weeks post intervention initiation and was partially mediated by parenting practices, caregiver mental health, and parenting stress at 8 weeks, but we found no evidence it was mediated by family cohesion, supporting two of our hypotheses.Equipping caregivers with parenting skills and strategies to improve mental health can go a long way in reducing overall parenting stress among caregivers with DBDs. Our findings could be leveraged to enhance stress reduction among caregivers of children with DBDs in the long-term.

Abstract Background Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 – 24 years seeking medical services at a major public hospital in Sierra Leone. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone between September 2022 and March 2023. We estimated the proportion of AHD in young PLHIV and performed logistic regression modelling to explore predictors of AHD. The statistical significance level was set at 0.05 for all statistical tests. Results Of the 581 PLHIV that were reported, 238 (40.9%) were between the ages of 15 and 24 years, with a median age of 22 (20—24), and 151 (63.5%) were females. On review, 178 (74.8%) has initiated antiretroviral therapy regimen (ART); 117 (65.7%) were actively on ART for ≤ 6 months, while 114 (64%) had interruptions with their ART treatment. The overall prevalence of AHD was 41.6% (99/238); 46.7% (35/68) of young PLHIV at the HIV clinic, and 39.3% (64/163) of admission. Sex—Female (OR, 0.51; 95% CI, 0.28–0.94; p = 0.030), and Tertiary Education level (OR, 0.27; 95% CI, 0.10 – 0.78; p = 0.015) have significantly lower odds of AHD in the entire study population. While for inpatients, Age (young Adults) of PLHIV (OR, 1.23; 95% CI, 1.00–1.52; p = 0.047) had 1.23 times the odds of AHD compared to adolescents, and being female (OR, 0.27; 95% CI, 0.08–0.84; p = 0.024), Overweight—Body mass index (OR, 0.10; 95% CI, 0.01–0.77; p = 0.028), Tertiary Education level (OR, 0.08; 95% CI, 0.01–0.52; p = 0.008) have significantly lower odds of AHD. Common conditions reported for the AHD group in the medical wards are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and oesophagal candidiasis (2.45%). Conclusion We reported a high prevalence of advanced HIV among young patients in a tertiary Hospital in Sierra Leone. One in two young PLHIV aged 15 to 24 years reported AHD, emphasizing the need to strengthen public health measures that address access to and retention of HIV services.

Abstract Background Children and adolescents who live in resource-limited communities in sub-Saharan Africa (SSA) experience significant mental health problems, including behavioral problems. In SSA, one of the most significant impediments to expanding services is a scarcity of mental health specialists. Task-shifting can effectively solve the mental health care gap in low-resource settings, yet it is underutilized in child and adolescent mental health. Moreover, the experiences of lay providers are understudied in global mental health, despite their potential impact on intervention effectiveness. In this study, we examined the experiences of community health workers and parent peers with the task-shifting of an evidence-based family strengthening intervention in Uganda. Methods As part of a larger randomized clinical trial, semi-structured in-depth interviews were conducted with 24 facilitators selected using stratified purposive sampling. Interviews explored their decision to participate in the program; experiences with the training; and experiences with intervention delivery. All interviews were conducted in Luganda (local language) and audio recorded. They were transcribed verbatim and translated into English. Thematic analysis was used to analyze the data. Results Despite concerns around lack of previous experience and time commitment, facilitators reported high relevance of the intervention to the families in their communities as well as their own as a motivation to participate. They also identified financial incentives as a motivating factor. These two factors also ensured their attendance at the training. They were satisfied with the content and skills provided during the training and felt prepared to deliver the intervention. During intervention delivery, they enjoyed seeing the families engaged and participating actively in the sessions as well as observing positive changes in the families. Some challenges with family attendance and engagement were noted. The facilitators reported an increased sense of self-efficacy and competence over time; and expressed high satisfaction with supervision. Conclusion Facilitators’ positive experiences point to the high acceptability and appropriateness of task-shifting this intervention in low-resource settings. As the global mental health field continues to be interested in task-shifting interventions to lay providers, successful examples should be studied so that evidence-based models can be put in place to support them through the process.

Abstract 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

Abstract Background The HIV burden remains a critical public health concern and adolescent girls are at significantly higher risk compared to the general adult population. Similar to other sub-Saharan African countries, Uganda reports high HIV prevalence among adolescent girls and young women. Yet, both evidence-based HIV prevention interventions and their acceptability among adolescent girls have not been widely studied. In this study, we examined the acceptability of the Suubi4Her intervention, an evidence-based combination intervention aimed at reducing HIV risk among adolescent girls in Uganda. Methods We conducted semi-structured in-depth interviews with 25 adolescent girls upon intervention completion to explore their experiences with the Suubi4Her intervention that was tested in a clinical trial in Uganda (2017–2023). Specifically, we explored their decision-making process for participating in the intervention, experiences with program attendance, and their feedback on specific intervention characteristics. Informed by the Theoretical Framework of Acceptability, the data were analyzed using thematic analysis. Results The main motivation for participation was access to health-related information, including information on STIs, HIV, and pregnancy as well as information on banking, saving, and income-generating activities. Though many participants did not have any initial concerns, mistrust of programs, initial paperwork, caregiver’s ability to commit time, concerns about ability to save, and HIV/STI and pregnancy testing were raised by some participants. Facilitators to session attendance included motivation to learn information, caregiver commitment, reminder calls, and incentives received for participation. The main challenges included household responsibilities and obligations, difficulty raising transport money, and weather challenges. Adolescent girls appreciated the group format and found the location and times of the sessions convenient. They also found the content relevant to their needs and noted positive changes in their families. Conclusions The results showed high intervention acceptability among adolescent girls. These findings have important programmatic and policy implications in Uganda, especially given the higher HIV prevalence among adolescent girls in the country. Trial registration NCT03307226 (Registered: 10/11/17).

Abstract Background Economic vulnerability influences women engaged in commercial sex work (WESW) to further engage in sexual risk behaviors, as they often have multiple customers and engage in unprotected sex for financial gains. This study examined asset ownership’s direct and indirect impact on sexual risk-taking behaviors among WESW in Southern Uganda, a very vulnerable group of women at high risk for contracting HIV and other STIs. Methodology We used baseline data from the Kyaterekera study, an NIH-funded study among WESW aged 18–55 across 19 HIV hotspots in Southern Uganda. Structural equation modeling was used to examine the direct, indirect, and total effects of assets—defined as ownership of physical and financial resources—on sexual risk-taking behaviors among WESW. Results Results showed that asset ownership was associated with a decrease in depression (β = − 0.096 [95% CI − 0.191, − 0.001], p = 0.050) and increased access to medical care (β = 0.174 [95% CI 0.072, 0.275], p = 0.001).We also found that an increase in access to medical care was associated with decreased sexual risk-taking behaviors (β = − 0.107 [95% CI − 0.210, − 0.004], p = 0.041). We observed a specific indirect effect between assets and sexual risk-taking behaviors through access to medical care (β = − 0.019 [95% CI − 0.040, − 0.002], p = 0.05). Mediation contributed 31% of the total effects of asset ownership on sexual risk-taking behaviors. Conclusion To our knowledge, this is among the few studies to examine the impact of asset ownership on sexual risk-taking behaviors among WESW in Southern Uganda. Findings from this study indicate that increasing access to economic resources may reduce the risk of WESW engaging in unprotected sex for higher income, which limits the spread of HIV among this population. The results also indicate that asset ownership may allow women to access healthcare services.

Abstract Background The global HIV burden remains a public health concern. Women engaged in sex work (WESW) are at higher risk of acquiring HIV compared to the general adult population. Uganda reports high rates of HIV prevalence among WESW. While WESW in Uganda have long been the subject of surveillance studies, they have not been targeted by theory-informed HIV prevention intervention approaches. In this study, we explored the perceived benefits of an evidence-based HIV risk reduction intervention that was implemented as part of a combination intervention tested in a clinical trial in Uganda. Methods As part of a larger randomized clinical trial, we conducted semi-structured in-depth interviews with 20 WESW selected using a stratified purposive sampling. All interviews were conducted in Luganda, language spoken in the study area, and audio-recorded. They were transcribed verbatim and translated to English. Thematic analysis was used to analyze the data. Results WESW’s narratives focused on: (1) condom use; (2) alcohol/drug consumption; (3) PrEP use; (4) “handling” customers; and (5) "massaging” customers. WESW agreed that male condom was one of the important learning points for them and planned to continue using them while female condoms were received with mixed reactions. Many women appreciated receiving information about the risks of consuming alcohol and drugs, and discussed how they reduced/ eliminated their consumption. PrEP information was appreciated though identified by fewer WESW. Handling a client was discussed as a helpful strategy for safer sex through improved ability to convince customers to use condoms or avoiding sex. Massaging was also beneficial to avoid penetrative sex, but similar to female condom, massaging also yielded mixed perceptions. Conclusion WESW found the intervention beneficial and described ways in which it improved their ability to engage in safer sex and stay healthy. The fact that WESW identified other strategies beyond condom use as helpful underlines the importance of adopting a comprehensive approach to behavioral interventions targeting HIV prevention even when combined with other interventions. Additionally, WESW’s narratives suggest that incorporating the tenets of social cognitive theory and harm reduction approaches in HIV prevention among this population can result in risk behavior change.

Abstract Background Sub-Saharan Africa (SSA) is heavily burdened by HIV, with 85% of the global new infections among adolescents happening in the region. With advances in medication and national policies promoting antiretroviral therapy (ART), children < 15 years living with HIV (CLWH) continue to grow with a chronic, highly stigmatized disease. Unfortunately, the stigma they experience results in much lower quality of life, including poor mental health and treatment outcomes. Family members also experience stigma and shame by virtue of their association with an HIV-infected family member. Yet, stigma-reduction interventions targeting CLWH and their families are very limited. The goal of this study is to address HIV-associated stigma among CLWH and their caregivers in Uganda. Methods This three-arm cluster randomized control trial, known as Suubi4Stigma, will evaluate the feasibility, acceptability, and preliminary impact of two evidence-based interventions: (1) group cognitive behavioral therapy (G-CBT) focused on cognitive restructuring and strengthening coping skills at the individual level and (2) a multiple family group (MFG) intervention that strengthens family relationships to address stigma among CLWH (N = 90, 10–14 years) and their families (dyads) in Uganda. Nine clinics will be randomized to one of three study arms (n = 3 clinics, 30 child-caregiver dyads each): (1) usual care; (2) G-CBT + usual care; and (3) MFG + usual care. Both treatment and control conditions will be delivered over a 3-month period. Data will be collected at baseline (pre-intervention) and at 3 months and 6 months post-intervention initiation. Conclusion The primary aim of the proposed project is to address the urgent need for theoretically and empirically informed interventions that seek to reduce HIV-associated stigma and its negative impact on adolescent health and psychosocial well-being. As several countries in SSA grapple with care and support for CLWH, this study will lay the foundation for a larger intervention study investigating how HIV-associated stigma can be reduced to foster healthy child development—especially for CLWH as they transition through adolescence. Trial registration ClinicalTrials.gov: NCT04528732 ; Registered August 27, 2020

Development of effective bivalent ligands has become the focus of intensive research toward modulation of G protein-coupled receptor (GPCR) oligomers, particularly in the field of GPCR pharmacology. Experimental studies have shown that they increased binding affinity and signaling potency compared to their monovalent counterparts, yet underlying molecular mechanism remains elusive. To address this, we performed accelerated molecular dynamics simulations on bivalent-ligand bound Adenosine 2A receptor (A2AR) dimer in the context of a modeled tetramer, which consists of A2AR and dopamine 2 receptor (D2R) homodimers and their cognate G proteins. Our results demonstrate that bivalent ligand impacted interactions between pharmacophore groups and ligand binding residues, thus modulating allosteric communication network and water channel formed within the receptor. Moreover, it also strengthens contacts between receptor and G protein, by modulating the volume of ligand binding pocket and intracellular domain of the receptor. Importantly, we showed that impact evoked by the bivalent ligand on A2AR dimer was also transmitted to apo D2R, which is part of the neighboring D2R dimer. To the best of our knowledge, this is the first study that provides a mechanistic insight into the impact of a bivalent ligand on dynamics of a GPCR oligomer. Consequently, this will pave the way for development of effective ligands for modulation of GPCR oligomers and hence treatment of crucial diseases such as Parkinson’s disease and cancer.

BackgroundYouth orphaned by HIV in sub-Saharan Africa experience immense hardships including social disadvantage, adverse childhood events and limited economic prospects. These adversities disrupt the normative developmental milestones and can gravely compromise their health and emotional wellbeing. The Bridges to the Future study (2012-2018) prospectively followed 1,383 adolescents, between 10-16 years, to evaluate the efficacy and cost-effectiveness of a family-based economic empowerment intervention comprising of child development accounts, financial literacy training, family income generating activities and peer mentorship. Study findings show efficacy of this contextually-driven intervention significantly improving mental health, school retention and performance and sexual health. However, critical questions, such as those related to the longitudinal impact of economic empowerment on HIV prevention and engagement in care remain. This paper presents a protocol for the follow-up phase titled, Bridges Round 2.MethodsThe Original Bridges study participants will be tracked for an additional four years (2022-2026) to examine the longitudinal developmental and behavioral health outcomes and potential mechanisms of the effect of protective health behaviors of the Bridges cohort. The study will include a new qualitative component to examine participants' experiences with the intervention, the use of biomedical data to provide the most precise results of the highly relevant, but currently unknown sexual health outcomes among study participants, as well as a cost-benefit analysis to inform policy and scale-up.DiscussionStudy findings may contribute to the scientific knowledge for low-resource communities on the potential value of providing modest economic resources to vulnerable boys and girls during childhood and early adolescence and how these resources may offer long-term protection against known HIV risks, poor mental health functioning and improve treatment among the HIV treatment care continuum.

BackgroundThe HIV burden remains a critical public health concern and women engaged in sex work [WESW] are at significantly higher risk compared to the general adult population. Similar to other sub-Saharan African countries, Uganda reports high rates of HIV prevalence among WESW. Yet, they have not been targeted by theory-informed HIV prevention intervention approaches.MethodsWe conducted semi-structured in-depth interviews with 20 WESW upon intervention completion to explore their experiences with an evidence-based HIV risk reduction intervention that was implemented as part of a combination intervention tested in a clinical trial in Uganda (2018-2023. Specifically, we explored their initial motivations and concerns for participating in the intervention, barriers and facilitators to attendance, and their feedback on specific intervention characteristics.ResultsThe main expectations revolved around access to health-related information, including information on STIs, HIV, and PrEP as well as on how one can protect themselves while engaging in sex work. Initial concerns were around potential breach of confidentiality and fear of arrest. The main facilitators for session attendance were the motivation to learn health-related information, the attitude of facilitators, and the incentives received for participation, whereas main challenges were related to family commitments and work schedules. WESW appreciated the group format of the intervention and found the location and times of the intervention delivery acceptable.Discussion and conclusionsOverall, our findings suggest that the HIV risk reduction intervention was appropriate and acceptable to WESW. Yet, WESW experience unique concerns and barriers that need to be accounted for when designing interventions targeting this population, especially in resource-limited settings where sex work is illegal and highly stigmatized.Clinical trial registrationNCT03583541.

Undruggability of RAS proteins has necessitated alternative strategies for the development of effective inhibitors. In this respect, phosphorylation has recently come into prominence as this reversible post-translational modification attenuates sensitivity of RAS towards RAF. As such, in this study, we set out to unveil the impact of phosphorylation on dynamics of HRASWT and aim to invoke similar behavior in HRASG12D mutant by means of small therapeutic molecules. To this end, we performed molecular dynamics (MD) simulations using phosphorylated HRAS and showed that phosphorylation of Y32 distorted Switch I, hence the RAS/RAF interface. Consequently, we targeted Switch I in HRASG12D by means of approved therapeutic molecules and showed that the ligands enabled detachment of Switch I from the nucleotide-binding pocket. Moreover, we demonstrated that displacement of Switch I from the nucleotide-binding pocket was energetically more favorable in the presence of the ligand. Importantly, we verified computational findings in vitro where HRASG12D/RAF interaction was prevented by the ligand in HEK293T cells that expressed HRASG12D mutant protein. Therefore, these findings suggest that targeting Switch I, hence making Y32 accessible might open up new avenues in future drug discovery strategies that target mutant RAS proteins.

BackgroundChildren in Sub-Saharan Africa are burdened by significant unmet mental health needs. Across the region, high rates of poverty, HIV/AIDS, food insecurity, stigma, and an inadequate health safety net system exacerbate serious child behavioral health needs and impede an effective response. Disruptive behavioral disorders are particularly concerning as they persist through adolescence and adulthood. Hence, addressing the context-specific social influences on child behavioral health is critical given that children in the region comprise more than half of the total regional population. Against this backdrop, this study protocol describes a randomized clinical trial that will examine the mechanisms by which economic empowerment and family strengthening interventions targeting social, familial, and context-specific drivers affect the mental health of children in Uganda.MethodsThe study uses an experimental, longitudinal design across 30 cluster-randomized primary schools to compare single and combination intervention options; influences of economic empowerment and family strengthening on economic, perceptual, and functioning mediators; and context-specific moderators. The study will be conducted with 900 Ugandan children in mid-upper primary school (10–14 years). The three study conditions (n = 300 each) are: (1) economic empowerment only (EE only), (2) multiple family group-based family strengthening only (MFG-based FS only), and (3) combined EE + MFG-based FS. The interventions will be provided for 12 months; and assessments will occur at baseline, 12, 24, and 36 months.ConclusionChildren in Sub-Saharan Africa are burdened by significant unmet mental health needs, including disruptive behavior disorders that persist through adolescence and adulthood if left untreated. The proposed study will examine the mechanisms by which economic empowerment and family strengthening interventions targeting social, familial and context-specific drivers affect the mental health of children in mid-upper primary schools in Uganda. Findings from this study can inform group, community, and population approaches that are needed for scalable solutions to address the social drivers negatively impacting child behavioral health in low-resource settings, including in Sub-Saharan Africa.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT053 68714].

BackgroundHIV stigma remains a formidable barrier to HIV treatment adherence among school-attending adolescents living with HIV, owing to high levels of HIV stigma within schools, rigid school structures and routines, lack of adherence support, and food insecurity. Thus, this protocol paper presents an evidence-informed multilevel intervention that will simultaneously address family- and school-related barriers to HIV treatment adherence and care engagement among adolescents living with HIV attending boarding schools in Uganda. ObjectiveThe proposed intervention—Multilevel Suubi (MSuubi)—has the following objectives: examine the impact of M-Suubi on HIV viral suppression (primary outcome) and adherence to HIV treatment, including keeping appointments, pharmacy refills, pill counts, and retention in care; examine the effect of M-Suubi on HIV stigma (internalized, anticipated, and enacted), with secondary analyses to explore hypothesized mechanisms of change (eg, depression) and intervention mediation; assess the cost and cost-effectiveness of each intervention condition; and qualitatively examine participants’ experiences with HIV stigma, HIV treatment adherence, and intervention and educators’ attitudes toward adolescents living with HIV and experiences with group-based HIV stigma reduction for educators, and program or policy implementation after training. MethodsMSuubi is a 5-year multilevel mixed methods randomized controlled trial targeting adolescents living with HIV aged 10 to 17 years enrolled in a primary or secondary school with a boarding section. This longitudinal study will use a 3-arm cluster randomized design across 42 HIV clinics in southwestern Uganda. Participants will be randomized at the clinic level to 1 of the 3 study conditions (n=14 schools; n=280 students per study arm). These include the bolstered usual care (consisting of the literature on antiretroviral therapy adherence promotion and stigma reduction), multiple family groups for HIV stigma reduction plus family economic empowerment (MFG-HIVSR plus FEE), and Group-based HIV stigma reduction for educators (GED-HIVSR). Adolescents randomized to the GED-HIVSR treatment arm will also receive the MFG-HIVSR plus FEE treatment. MSuubi will be provided for 20 months, with assessments at baseline and 12, 24, and 36 months. ResultsThis study was funded in September 2021. Participant screening and recruitment began in April 2022, with 158 dyads enrolled as of May 2022. Dissemination of the main study findings is anticipated in 2025. ConclusionsMSuubi will assess the effects of a combined intervention (family-based economic empowerment, financial literacy education, and school-based HIV stigma) on HIV stigma among adolescents living with HIV in Uganda. The results will expand our understanding of effective intervention strategies for reducing stigma among HIV-infected and noninfected populations in Uganda and improving HIV treatment outcomes among adolescents living with HIV in sub-Saharan Africa. Trial RegistrationClinicalTrials.gov NCT05307250; https://clinicaltrials.gov/ct2/show/NCT05307250 International Registered Report Identifier (IRRID)PRR1-10.2196/40101

Abstract Background Youth living with HIV (YLHIV) in Sub-Saharan African (SSA) are less likely to adhere to antiretroviral therapy (ART) and other health-related regimens. As a consequence, YLHIV are not only at risk for health problems and mental health comorbidities, but are also at risk for cognitive deficits, including in areas of memory and executive functioning. The Suubi+Adherence study followed 702 adolescents (10-16 years of age) receiving bolstered standard of care and a family economic empowerment intervention comprising an incentivized youth financial savings account (YSA) augmented with financial literacy training (FLT) and peer mentorship. The study findings pointed to superior short-term viral suppression and positive adolescent health and mental health functioning among participants receiving the intervention. The original group of adolescents who received Suubi+Adherence are now transitioning into young adulthood. This paper presents a protocol for the follow-up phase titled Suubi+Adherence Round 2. Methods The original cohort in Suubi+Adherence will be tracked for an additional five years (2020-2025). Specifically, the long term follow-up will allow to: 1) ascertain the extent to which the short term outcomes identified in the first 6 years of the intervention are maintained as the same group transitions through young adulthood; and 2) address new scientific questions regarding ART adherence; HIV care engagement; protective health behaviors; and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. Additionally, the team examines the potential mechanisms through which the observed long-term outcomes happen. Moreover, the Suubi+Adherence-Round 2 adds a qualitative component and extends the cost effectiveness component. Discussion Guided by asset and human development theories, Suubi+Adherence-R2 will build on the recently concluded Suubi+Adherence study to conduct one of the largest and longest running studies of YLHIV in SSA as they transition into young adulthood. The study will address new scientific questions regarding long-term ART adherence, HIV care engagement, protective health behaviors, and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. The findings may inform efforts to improve HIV care among Uganda’s YLHIV, with potential replicability in other low-resource countries. Trial registration ClinicalTrials.gov , ID: NCT01790373

Abstract Background The International Labor Organization (ILO) estimates that 11% of children (ages 5 to 17) worldwide are child laborers. ILO recently drew attention to migrant child laborers as an underreported, but more vulnerable group to adverse outcomes relative to children working locally. Sub-Saharan Africa (SSA) continues to be the continent with the highest rates of child labor, with Ghana registering one of the highest incidence rates at 22%, including unaccompanied child migrants engaged in labor. Adolescent girls make up the majority of unaccompanied rural-to-urban migrants in search of better economic opportunities. Studies document the myriad of serious threats to health and emotional well-being experienced by adolescent girls who migrate to engage in child labor. These threats underline the urgent need for theoretically informed preventive interventions, specifically tailored to address the root causes of female child migrant labor and the needs of girls from economically insecure families and communities. Methods A two-arm cluster randomized control trial will be conducted to assess the feasibility, acceptability, and preliminary impact of ANZANSI (family economic empowerment + multiple family groups) among 100 adolescent girls and their caregivers in the Northern Region of Ghana. Ten schools will be randomly selected from a list of eligible schools, and randomized to one of two study arms: (1) control arm (n = 5 schools, n = 50 adolescent-caregiver dyads); (2) treatment arm (n = 5 schools, n = 50 adolescent-caregiver dyads) receiving ANZANSI over a 9-month period. Adolescents (ages 11 to 14) in the same school will be assigned to the same study condition to avoid contamination. Discussion The primary aim of the study is to address the urgent need for theoretically and empirically informed interventions that prevent adolescent girls’ unaccompanied rural-to-urban migration for child labor. Existing programs are not preventive and primarily target children who already migrated to the city and are living and working on the streets. This study is one of the first studies to pilot test a combination intervention, integrating family economic empowerment targeting household poverty with multiple family groups addressing family cohesion and perceptions on gender norms, child education/labor, all of which are factors, when combined, force girls to drop out of school and migrate. Trial registration ClinicalTrials.gov ; NCT04231669 ; Registered January 18, 2020;

Abstract Background Adolescents living with HIV in sub-Saharan Africa are a vulnerable group at the intersection of poverty and health disparities. The family is a vital microsystem that provides financial and emotional support to achieve optimal antiretroviral therapy (ART) adherence. In this study, we explore the association between family factors and ART adherence self-efficacy, a significant psychological concept playing a critical role in ART adherence. Methods Data from an NIH-funded study called Suubi + Adherence, an economic empowerment intervention for HIV positive adolescents (average age = 12.4 years) in southern Uganda was analyzed. We conducted multilevel regression analyses to explore the protective family factors, measured by family cohesion, child-caregiver communication and perceived child-caregiver support, associated with ART adherence self-efficacy. Results The average age was 12.4 years and 56.4% of participants were female. The average household size was 5.7 people, with 2.3 children> 18 years. Controlling for sociodemographic and household characteristics, family cohesion (β = 0.397, p = 0.000) and child-caregiver communication (β = 0.118, p = 0.026) were significantly associated with adherence self-efficacy to ART. Conclusion Findings point to the need to strengthen family cohesion and communication within families if we are to enhance adherence self-efficacy among adolescents living with HIV. Trial registration This trial was registered with ClinicalTrials.gov (registration number: NCT01790373 ) on 13 February 2013.

Summary: Background: Women engaged in sex work (WESW) are disproportionately affected by HIV. In Uganda, HIV prevalence among WESW is estimated at 37%, accounting for 18% of all new infections in the country. WESW experience poverty, gender-based violence, and other issues that reduce their power and limit their ability to negotiate condom use. Female-controlled strategies, including pre-exposure prophylaxis (PrEP), may afford women more transmission protection, but barriers to access and use persist. This cross-sectional study examined baseline PrEP acceptability and initiation among WESW recently enrolled in a randomized clinical trial in Uganda to test the impact of a combination HIV risk reduction and economic empowerment intervention on sexual risk outcomes (clinicaltrials.gov, NCT03583541). Methods: A total of 542 WESW from 19 high HIV-prevalent geographical areas were enrolled in the Kyaterekera study between June 2019 and March 2020. Women were eligible for the study if they: (1) were age 18 or over; (2) reported engagement in transactional sex (a sex act in exchange for pay) in the past 30 days; and (3) reported engagement in one or more episodes of unprotected sex in the past 30 days. Women completed a baseline assessment, were tested for HIV and other sexually transmitted infections (STIs) at enrollment, and were connected with antiretroviral therapy (ART), STI treatment, or PrEP, based on need and interest. Descriptive statistics examined baseline data on PrEP acceptability and initiation. Independent variables (i.e. years in sex work, recent sexual coercion, perceived HIV and sex work stigmas, harmful alcohol use, barriers to medical care, and social support) were derived from the empirical literature and women's self-report. Bivariate analysis was performed to test associations between main effects of these variables. Using binomial logistic regression, predictive models were evaluated for two distinct outcomes—PrEP acceptability and PrEP initiation/uptake. Findings: At baseline, 59% of women (n = 322) tested HIV negative. Among WESW testing negative, 11% (n = 36) were already PrEP enrolled. Most women reported willingness to use PrEP (n = 317; 91%). Slightly over half of WESW not already on PrEP agreed to initiate PrEP (n = 158; 55%). Logistic regression models demonstrate that acceptability of or willingness to use PrEP was significantly associated with fewer years engaged in sex work (AOR= ·18, 95% CI 0·05-·66, p

IntroductionWomen engaged in sex work (WESW) have an elevated risk of the human immunodeficiency virus (HIV) and sexually transmitted infections (STI). Estimates are three times higher than the general population. Understanding the predictors of HIV and STI among WESW is crucial in developing more focused HIV and STI prevention interventions among this population. The study examined the prevalence and predictors of HIV and STI among WESW in the Southern part of Uganda.MethodologyBaseline data from the Kyaterekera study involving 542 WESW (ages 18-55) recruited from 19 HIV hotspots in the greater Masaka region in Uganda was utilized. HIV and STI prevalence was estimated using blood and vaginal fluid samples bioassay. Hierarchical regression models were used to determine the predictors of HIV and STI among WESW.ResultsOf the total sample, 41% (n = 220) were found to be HIV positive; and 10.5% (n = 57) tested positive for at least one of the three STI (Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis) regardless of their HIV status. Older age (b = 0.09, 95%CI = 0.06, 0.13, p≤0.001), lower levels of education (b = -0.79, 95%CI = -1.46, -0.11, p≤0.05), fewer numbers of children in the household (b = -0.18, 95%CI = -0.36, -0.01), p≤0.05), location (i.e., fishing village (b = 0.51, 95%CI = 0.16, 0.85, p≤0.01) or small town (b = -0.60, 95%CI = -0.92, -0.28, p≤0.001)), drug use (b = 0.58, 95%CI = 0.076, 1.08, p≤0.05) and financial self-efficacy (b = 0.05, 95%CI = -0.10, 0.00, p≤0.05), were associated with the risk of HIV infections among WESW. Domestic violence attitudes (b = -0.24, 95%CI = -0.42, -0.07, p≤0.01) and financial distress (b = -0.07, 95%CI = -0.14, -0.004, p≤0.05) were associated with the risk of STI infection among WESW.ConclusionStudy findings show a high prevalence of HIV among WESW compared to the general women population. Individual and family level, behavioural and economic factors were associated with increased HIV and STI infection among WESW. Therefore, there is a need for WESW focused HIV and STI risk reduction and economic empowerment interventions to reduce these burdens.

Background: There is a critical need to address mental health needs across the globe, especially in low and middle-income countries where mental health disparities are pervasive, including among children. The global mental health disparities suggest an imperative for culturally and contextually-congruent mental health services models that expand upon the existing services and interventions for these groups. Rigorous research is a key tool in providing the scientific evidence to inform public policy and practice efforts to effectively address these needs. Yet, there is a limited number of researchers, especially those from diverse backgrounds, who study these issues. In this paper, we describe the “TrainingLEADers to Accelerate Global Mental Health Disparities Research” (LEAD) program, a research training program funded by the National Institute on Minority Health and Health Disparities and focused on global mental health disparities research for early career researchers from under-represented minority groups.Methods: The LEAD program is designed as a two-phase training program for advanced pre-doctoral students, postdoctoral fellows, and junior faculty from diverse backgrounds in the U.S., including groups underrepresented in biomedical, behavioral, clinical and social sciences research, interested in global mental health disparities research. Trainees are matched with mentors and participate in an intensive 12-week program.Discussion: The LEAD program seeks to provide a robust platform for the development, implementation and expansion of evidence-based culturally and contextually-congruent interventions and services models addressing global mental health disparities across the life cycle, especially in low-resource communities in the global context. By producing a sustainable network of well-trained investigators from underrepresented backgrounds, LEAD will potentially contribute to the shared lessons and efforts relevant to addressing global mental health disparities and improving care for vulnerable populations in low-resource settings.

Abstract Background Sub-Saharan Africa (SSA) has the highest number of people living with HIV/AIDS, with Nigeria, South Africa, and Uganda accounting for 48% of new infections. A systematic review of the HIV burden among women engaged in sex work (WESW) in 50 low- and middle-income countries found that they had increased odds of HIV infection relative to the general female population. Social structural factors, such as the sex work environment, violence, stigma, cultural issues, and criminalization of sex work are critical in shaping sexually transmitted infection (STI)/HIV risks among WESW and their clients in Uganda. Poverty is the most commonly cited reason for involvement in sex work in SSA. Against this backdrop, this study protocol describes a randomized controlled trial (RCT) that tests the impact of adding economic empowerment to traditional HIV risk reduction (HIVRR) to reduce new incidence of STIs and HIV among WESW in Rakai and the greater Masaka regions in Uganda. Methods This three-arm RCT will evaluate the efficacy of adding savings, financial literacy and vocational training/mentorship to traditional HIVRR on reducing new incidence of STI infections among 990 WESW across 33 hotspots. The three arms (n = 330 each) are: 1) Control group: only HIVRR versus 2) Treatment group 1: HIVRR plus Savings plus Financial Literacy (HIVRR + S + FL); and 3) Treatment group 2: HIVRR plus S plus FL plus Vocational Skills Training and Mentorship (V) (HIVRR + S + FL + V). Data will be collected at baseline (pre-test), 6, 12, 18 and 24-months post-intervention initiation. This study will use an embedded experimental mixed methods design where qualitative data will be collected post-intervention across all conditions to explore participant experiences. Discussion When WESW have access to more capital and/or alternative forms of employment and start earning formal income outside of sex work, they may be better able to improve their skills and employability for professional advancement, thereby reducing their STI/HIV risk. The study findings may advance our understanding of how best to implement gender-specific HIV prevention globally, engaging women across the HIV treatment cascade. Further, results will provide evidence for the intervention’s efficacy to reduce STIs and inform implementation sustainability, including costs and cost-effectiveness. Trial registration ClinicalTrials.gov, ID: NCT03583541.

Abstract Background Disruptive Behavioral Disorders (DBDs) and Attention Deficit/Hyperactivity Disorder (ADHD) are chronic, impairing, and costly child and adolescent mental health challenges which, when untreated, can result in disruptions in school performance, friendships and family relations. Yet, there is dearth of prevalence data on child and adolescent behavioral challenges within sub-Saharan Africa, including Uganda. This study aims to estimate the prevalence rate of behavioral challenges and ADHD among young school going children and early adolescents (ages 8–13 at study enrollment), utilizing a school-based sample in southwest Uganda. Methods We present screening results from a 5-year scale-up study titled SMART Africa-Uganda (2016–2021), set across 30 public primary schools located in the greater Masaka region in Uganda, a region heavily impacted by poverty and HIV/AIDS. Specifically, we draw on screening data from caregivers of 2434 children that used well-established standardized measures that had been pre-tested in the region. These were: 1) oppositional defiant disorder (ODD) and conduct disorder (CD) subscales of the Disruptive Behavior Disorders (DBD) scale; and 2) the Iowa Connors and Impairment scales. Slightly over half of the children in the sample were female (52%), with a mean age of 10.27 years. Results Of the 2434 participants screened for disruptive behaviors: 1) 6% (n = 136) scored positive on ODD and 2% (n = 42) scored positive on CD subscales of the DBD scale; 2) 9.61% (n = 234), and 2.67% (n = 65) were reported to have elevated symptoms of ODD and ADHD on the Iowa Connors caregiver report scale respectively. Twenty-five percent (n = 586) of children were described by their caregivers as having experienced some form of impairment in at least four domains of the Impairment scale. Conclusion The results indicate the presence of behavioral challenges and ADHD among school going children, aged 8–13 years, in Uganda. Given the negative outcomes associated with behavioral challenges as children transition to adolescence and adulthood, detecting these emerging behavioral challenges early is critical in developing appropriate interventions. School settings could be considered as one of the contextually-relevant, culturally-appropriate, and non-stigmatizing venues to implement screening procedures and to detect emerging behavioral challenges and to make necessary referrals.

Background: Uganda has one of the highest HIV/AIDS rates and poor mental health services. Children and adolescents in communities with persistent poverty, disease (including HIV/AIDS), and violence, are more likely to suffer from chronic mental health problems. Combined, these characteristics negatively impact communities' response to HIV and mental health beginning with children, adolescents, and young adults. Yet, there is limited research capacity in child and adolescent mental health (CAMH), especially in the HIV/AIDS context in Uganda. Hence, this NIH-funded research training program aims to: (1) train three cohorts of early-career investigators at universities or research institutions in Uganda; (2) connect fellows with committed mentors; and (3) define key factors for successful mentorship and training of new investigators.Methods: CHILD-GRF is a multi-component program that engages selected young investigators in year-round activities for 3 years. Paired with mentors from Washington University in St. Louis and academic institutions in Uganda, fellows participate in a 6-week intensive summer training each year. Year 1 focuses on didactic learning and mentorship. In Year 2, fellows design and conduct their pilot study. Year 3 is devoted to presenting pilot study findings, manuscript preparation/ submission and extramural grant writing.Discussion: CHILD-GRF seeks to provide a solid foundation for the development and implementation of evidence-based HIV prevention and mental health interventions for youth and families impacted by HIV/AIDS. By producing a sustainable network of well-trained individuals in key research institutions, this program contributes to improving CAMH and HIV prevention efforts, both of which have public health implications.

Youth Living with HIV/AIDS (YLWHIV) have a higher risk of developing immunodeficiency related illnesses including certain cancers than their general population counterparts of the same age. This narrative review of current available literature describes factors associated with pediatric access to oncological services, and the role economic strengthening could play in improving health outcomes for this vulnerable population. Findings suggest that both HIV-infected and -uninfected children living in low and middle-income countries struggle with access and adherence to cancer treatment and care. Cost of treatment is a major barrier to access and adherence. Asset-building savings programs may increase financial security and subsequently result in better health outcomes although they have not been utilized to improve access to cancer treatment.

HIV-related stigma has been documented as one of the greatest obstacles to reducing HIV spread, engagement in HIV treatment, and poor mental health functioning among people living with HIV (PLWH). Although disclosure is important for people to receive social support, the fear of stigma and discrimination prevents PLWH from disclosing their status. For children and adolescents growing up with HIV –with no opportunity for normal transition through adolescence due to stigma, it is important to identify additional family and community support systems, to improve their acceptance and health outcomes, including mental health functioning. This study examined family communication and social support factors associated with HIV disclosure and HIV-related stigma among children and adolescents living with HIV in Uganda. Baseline data from an NICHD-funded Suubi+Adherence study (N=702) were analyzed. Adolescents (10–16 years) were eligible to participate if they were: 1) HIV positive and knew their HIV status, 2) prescribed antiretroviral therapy, 3) lived within a family, not an institution, and 4) enrolled in one of the 39 health centers in the study area. Multiple regression analyses were conducted to determine family communication (frequency and level of comfort communicating with caregiver), social support (perceived child-caregiver support and social support from classmates, close friends, teachers, and caregivers), associated with HIV disclosure, disclosure comfort, and HIV internalized and anticipated stigma. Results show that level of comfort communicating with a caregiver was significantly associated with how often children discussed their HIV status with other people (B = 0.02, 95% CI = 0.00, 0.03, p = 0.04), and level of HIV disclosure comfort (B = 0.08, 95% CI = 0.04, 0.13, p < 0.01). In addition, support from within the school environment, i.e., from teachers and classmates, was uniquely associated with both HIV disclosure and HIV-related stigma. Findings point to schools as potential for implementing HIV stigma-reduction programs. In addition, programming aimed at improving HIV care and treatment outcomes for adolescents living with HIV should consider incorporating both family communication strengthening and HIV-stigma reduction strategies in their efforts, in order to improve HIV health-related outcomes, including overall mental health functioning of HIV positive adolescents.

Abstract Background Children in Sub-Saharan Africa (SSA) comprise half of the total regional population, yet existing mental health services are severely under-equipped to meet their needs. Although effective interventions for the treatment of disruptive behavioral disorders (DBDs) in youth have been tested in high-poverty and high-stress communities in developed countries, and are relevant for widespread dissemination in low- and middle-income countries (LMICs), most of these evidence-based practices (EBPs) have not been utilized in SSA, a region heavily impacted by poverty, diseases including HIV/AIDS, and violence. Thus, this paper presents a protocol for a scale-up longitudinal experimental study that uses a mixed-methods, hybrid type II, effectiveness implementation design to test the effectiveness of an EBP, called Multiple Family Group (MFG) aimed at improving child behavioral challenges in Uganda while concurrently examining the multi-level factors that influence uptake, implementation, sustainment, and youth outcomes. Methods The MFG intervention will be implemented and tested via a longitudinal experimental study conducted across 30 public primary schools located in both semi-urban and rural communities. The schools will be randomly assigned to three study conditions (n = 10 per study condition): (1) MFG delivered by trained family peers; (2) MFG delivered by community health workers; or; (3) comparison: usual care comprising mental health care support materials, bolstered with school support materials. A total of 3000 children (ages 8 to 13 years; grades 2 to 7) and their caregivers (N = 3000 dyads); 60 parent peers, and 60 community health workers will be recruited. Each study condition will comprise of 1000 child-caregiver dyads. Data will be collected at baseline, 8 and 16 weeks, and 6-month follow-up. Discussion This project is the first to test the effectiveness of the MFG intervention while concurrently examining multi-level factors that influence overall implementation of a family-based intervention provided in schools and aimed at reaching the large child population with mental health service needs in Uganda. Moreover, the study draws upon an EBP that has already been tested for delivery by parent peers and community facilitators, and hence will take advantage of the advancing science behind task-shifting. If successful, the project has great potential to address global child mental health needs. Trial registration ClinicalTrials.gov, ID: NCT03081195. Registered on 16 March 2017.

Abstract Background Asset-based economic empowerment interventions, which take an integrated approach to building human, social, and economic capital, have shown promise in their ability to reduce HIV risk for young people, including adolescent girls, in sub-Saharan Africa. Similarly, community and family strengthening interventions have proven beneficial in addressing mental health and behavioral challenges of adolescents transitioning to adulthood. Yet, few programs aimed at addressing sexual risk have applied combination interventions to address economic stability and mental health within the traditional framework of health education and HIV counseling/testing. This paper describes a study protocol for a 5-year, NIMH-funded, cluster randomized-controlled trial to evaluate a combination intervention aimed at reducing HIV risk among adolescent girls in Uganda. The intervention, titled Suubi4Her, combines savings-led economic empowerment through youth development accounts (YDA) with an innovative family strengthening component delivered via Multiple Family Groups (MFG). Methods Suubi4Her will be evaluated via a three-arm cluster randomized-controlled trial design (YDA only, YDA + MFG, Usual Care) in 42 secondary schools in the Central region of Uganda, targeting a total of 1260 girls (ages 15–17 at enrollment). Assessments will occur at baseline, 12, 24, and 36 months. This study addresses two primary outcomes: 1) change in HIV risk behavior and 2) change in mental health functioning. Secondary exploratory outcomes include HIV and STI incidence, pregnancy, educational attainment, financial savings behavior, gender attitudes, and self-esteem. For potential scale-up, cost effectiveness analysis will be employed to compare the relative costs and outcomes associated with each study arm. Conclusions Suubi4Her will be one of the first prospective studies to examine the impact and cost of a combination intervention integrating economic and social components to reduce known HIV risk factors and improve mental health functioning among adolescent girls, while concurrently exploring mental health as a mediator in HIV risk reduction. The findings will illuminate the pathways that connect economic needs, mental health, family support, and HIV risk. If successful, the results will promote holistic HIV prevention strategies to reduce risk among adolescent girls in Uganda and potentially the broader sub-Saharan Africa region. Trial registration Clinical Trials NCT03307226 (Registered: 10/11/17).

BackgroundThe rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment.MethodsWe carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect of a family economic empowerment (EE) intervention on viral suppression in five districuts in Uganda. In total, 39 accredited health care clinics from study districts with existing procedures tailored to adolescent adherence were eligible to participate in the trial. We used data from 288 youth with detectable HIV viral loads (VL) at baseline (158 -intervention group from 20 clinics, 130 -non-intervention group from 19 clinics). The primary end point was undetectable plasma HIV RNA levels, defined as < 40 copies/ml. We used Kaplan-Meier (KM) analysis and Cox proportional hazard models to estimate intervention effects.FindingsThe Kaplan-Meier (KM) analysis indicated that an incidence of undetectable VL (0.254) was significantly higher in the intervention condition compared to 0.173 (in non-intervention arm) translated into incidence rate ratio of 1.468 (CI: 1.064-2.038), p = 0.008. Cox regression results showed that along with the family-based EE intervention (adj. HR = 1.446, CI: 1.073-1.949, p = 0.015), higher number of medications per day had significant positive effects on the viral suppression (adj.HR = 1.852, CI: 1.275-2.690, p = 0.001).InterpretationA family economic empowerment intervention improved treatment success for ALWHIV in Uganda. Analyses of cost effectiveness and scalability are needed to advance incorporation of this intervention into routine practice in low and middle-income countries.

Youth Living with HIV (YLWHIV) are at high risk for cancer. Sub-Saharan Africa (SSA) has some of the worst pediatric cancer survival rates due to barriers to accessing cancer services and treatment adherence. This protocol describes a study that aims at: 1) Identifying confirmed and suspected cancer cases in a cohort of >3000 HIV positive youth; 2) Examining the short-term preliminary outcomes of an evidence-based Economic Empowerment (EE) intervention, Suubi (“hope” in a local Ugandan language), on access to pediatric cancer diagnosis and care, and treatment adherence among YLWHIV with suspected cancers in Uganda; and 3) Exploring multi-level factors impacting intervention participation and experiences. The proposed Suubi4Cancer intervention combines savings-led EE through family development accounts (FDA) with financial literacy and management (FLM) and cancer education (CE). The study will review medical charts in 39 clinics in Southwest Uganda to identify confirmed and suspected cancer cases. Subsequently, Suubi4Cancer will be evaluated via a randomized-controlled trial design (FDA + FLM + CE versus Usual Care) targeting a total of 78 youth ages 10-to-24 and their caregivers. Assessments at baseline and 9 months will examine change in cancer treatment access; cancer treatment adherence; and knowledge, attitudes, and beliefs about cancer and cancer treatment. Semi-structured interviews with the intervention group will explore their intervention experiences. To our knowledge, Suubi4Cancer will be the first study to test the preliminary impact and acceptability of a combination intervention to increase access to cancer diagnosis and treatment services for YLWHIV. Trial registration: Clinical Trials NCT03916783 (Registered: 04/16/19). Keywords: Pediatric cancer, HIV/AIDS, Children and youth, Sub-saharan africa, Economic empowerment, Access to treatment services

Background: Globally, 1.8 million children

BackgroundChildren who have lost a parent to HIV/AIDS, known as AIDS orphans, face multiple stressors affecting their health and development. Family economic empowerment (FEE) interventions have the potential to improve these outcomes and mitigate the risks they face. We present efficacy and cost-effectiveness analyses of the Bridges study, a savings-led FEE intervention among AIDS-orphaned adolescents in Uganda at four-year follow-up.MethodsIntent-to-treat analyses using multilevel models compared the effects of two savings-led treatment arms: Bridges (1:1 matched incentive) and BridgesPLUS (2:1 matched incentive) to a usual care control group on the following outcomes: self-rated health, sexual health, and mental health functioning. Total per-participant costs for each arm were calculated using the treatment-on-the-treated sample. Intervention effects and per-participant costs were used to calculate incremental cost-effectiveness ratios (ICERs).FindingsAmong 1,383 participants, 55% were female, 20% were double orphans. Mean age was 12 years at baseline. At 48-months, BridgesPLUS significantly improved self-rated health, (0.25, 95% CI 0.06, 0.43), HIV knowledge (0.21, 95% CI 0.01, 0.41), self-concept (0.26, 95% CI 0.09, 0.44), and self-efficacy (0.26, 95% CI 0.09, 0.43) and lowered hopelessness (-0.28, 95% CI -0.43, -0.12); whereas Bridges improved self-rated health (0.26, 95% CI 0.08, 0.43) and HIV knowledge (0.22, 95% CI 0.05, 0.39). ICERs ranged from $224 for hopelessness to $298 for HIV knowledge per 0.2 standard deviation change.ConclusionsMost intervention effects were sustained in both treatment arms at two years post-intervention. Higher matching incentives yielded a significant and lasting effect on a greater number of outcomes among adolescents compared to lower matching incentives at a similar incremental cost per unit effect. These findings contribute to the evidence supporting the incorporation of FEE interventions within national social protection frameworks.

Cancer is the second leading cause of death worldwide. The etiology of the disease has remained elusive, but mutations causing aberrant RNA splicing have been considered one of the significant factors in various cancer types. The association of aberrant RNA splicing with drug/therapy resistance further increases the importance of these mutations. In this work, the impact of the splicing factor 3B subunit 1 (SF3B1) K700E mutation, a highly prevalent mutation in various cancer types, is investigated through molecular dynamics simulations. Based on our results, K700E mutation increases flexibility of the mutant SF3B1. Consequently, this mutation leads to i) disruption of interaction of pre-mRNA with SF3B1 and p14, thus preventing proper alignment of mRNA and causing usage of abnormal 3’ splice site, and ii) disruption of communication in critical regions participating in interactions with other proteins in pre-mRNA splicing machinery. We anticipate that this study enhances our understanding of the mechanism of functional abnormalities associated with splicing machinery, thereby, increasing possibility for designing effective therapies to combat cancer at an earlier stage.

# Background Post exposure prophylaxis remains the single most important means of decreasing HIV infection upon occupational exposure. It offers over 80% protection against HIV sero-conversion when initiated within 72 hours of exposure and if the treatment regimen followed diligently for 28 days. This study assessed the level of knowledge and usage of post exposure prophylaxis among healthcare workers in the Eastern Regional Hospital, Koforidua, Ghana where HIV prevalence is high. # Methods A cross-sectional study was conducted among 185 HealthCare Workers (HCWs) between May and July 2016. Data was collected using self-administered structured questionnaires and analyzed with Stata-13. Bivariate associations were tested using chi-square or Fisher's exact test as appropriate. Multivariate analysis was conducted with logistic regression. A *P*-value of ≤0.05 was considered statistically significant. # Results Out of the 185 HCW interviewed, 96.8% considered themselves at risk of occupational exposure with 83.2% reporting occupational exposure within the last 12 months. Nearly all participants (97.3%) knew about the existence of post exposure prophylaxis (PEP). A majority (90.8%) acknowledged the effectiveness of PEP in preventing HIV infection. About 89% knew that the exposed area should be washed with soap and water or flushed with copious amounts of water and 65.4% knew whom to contact after exposure. Although about 93% knew PEP should be started within 72 hours of exposure, only 38.9% knew the duration of treatment to be four weeks. The accurate drug regime following a high-risk needle stick injury was known by 25.1% while the proportion of needle stick injuries could result in HIV transmission was unknown by 65.9%. Although 51.9% were eligible to take PEP, only 33.8% reported having received PEP. # Conclusions Despite high levels of knowledge of the effectiveness of HIV PEP, the appropriate first aid to perform and the time of commencement of PEP, Usage of PEP was low among HCWs despite the high prevalence of occupational injuries. Training to prevent occupational exposure, increase the level of knowledge and use of PEP is recommended.

G protein-coupled receptors (GPCRs) are involved in a wide variety of physiological processes. Therefore, approximately 40% of currently prescribed drugs have targeted this receptor family. Discovery of β -arrestin mediated signaling and also separability of G protein and β -arrestin signaling pathways have switched the research focus in the GPCR field towards development of biased ligands, which provide engagement of the receptor with a certain effector, thus enriching a specific signaling pathway. In this review, we summarize possible factors that impact signaling profiles of GPCRs such as oligomerization, drug treatment, disease conditions, genetic background, etc. along with relevant molecules that can be used to modulate signaling properties of GPCRs such as allosteric or bitopic ligands, ions, aptamers and pepducins. Moreover, we also discuss the importance of inclusion of pharmacogenomics and molecular dynamics simulations to achieve a holistic understanding of the relation between genetic background and structure and function of GPCRs and GPCR-related proteins. Consequently, specific downstream signaling pathways can be enriched while those that bring unwanted side effects can be prevented on a patient-specific basis. This will improve studies that centered on development of safer and personalized therapeutics, thus alleviating the burden on economy and public health.

While significant progress has been made in improving the wellbeing of women and girls around the world, a gender gap still exists between men and women which is very evident in Ghana. Gender inequalities continue to persist in Ghana because of cultural gender norms that exalt and favor men and put women in subordinate and subservient roles. These cultural gender norms hinder women's development and widen gender inequality between men and women in different system levels of society. Therefore, there is a need to examine the influence of these cultural gender norms on women's lives using a systems framework to capture a full picture of women's experiences at these systemic levels of society. In this paper, we use Bronfenbrenner's ecological systems multilevel approach to examine the impact of these cultural gender norms on women's lives at the different system levels. We conducted a desk review of studies published in sub-Saharan Africa focused on cultural gender norms and gender inequality. The findings showed that the impact of cultural gender norms on gender inequality at the levels of the four social systems (microsystem, mesosystem, exosystem, and macrosystem) are interconnected, creating and widening the inequality gap between men and women. Cultural gender norms influence gender role socialization in the home, which then transmits to the school and religious institutions as the mesosystem. At the school level, cultural gender norms act as a mesosystem manifest through discriminatory classroom practices, gender role assignment of school responsibilities, and gender role representations in textbooks. In Christianity and Islam, cultural gender norms create doctrines that enforce men's domination over women, and, in the workplace, cultural gender norms have gendered labor by defining a man's occupation and limiting women to domestic and low-paying occupations. The mass media is the exosystem that displays images of women to fit cultural gender norms of what is defined as acceptable for women. Finally, the macrosystem is the overall sociocultural norms that have been accepted by society that perpetuate discriminatory practices against women. Keywords: Cultural gender norms, Ecological systems theory, Gender inequality, Ghana, Introduction Human development is the capability of all individuals, irrespective of gender, to have dignity, self-determination, freedom from discrimination, good health, and access to knowledge, human security, a decent standard [...]