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Acute respiratory illness (ARI) is one of the most common reasons children receive antibiotic treatment. Measurement of C-reaction protein (CRP) has been shown to reduce unnecessary antibiotic use among children with ARI in a range of clinical settings. In many resource-constrained contexts, patients seek care outside the formal health sector, often from lay community health workers (CHW). This study's objective was to determine the impact of CRP measurement on antibiotic use among children presenting with febrile ARI to CHW in Uganda. We conducted a cross-sectional, stepped wedge cluster randomized trial in 15 villages in Bugoye subcounty comparing a clinical algorithm that included CRP measurement by CHW to guide antibiotic treatment (STAR Sick Child Job Aid [SCJA]; intervention condition) with the Integrated Community Care Management (iCCM) SCJA currently in use by CHW in the region (control condition). Villages were stratified into 3 strata by altitude, distance to the clinic, and size; in each stratum, the 5 villages were randomly assigned to one of 5 treatment sequences. Children aged 2 months to 5 years presenting to CHW with fever and cough were eligible. CHW conducted follow-up assessments 7 days after the initial visit. Our primary outcome was the proportion of children who were given or prescribed an antibiotic at the initial visit. Our secondary outcomes were (1) persistent fever on day 7; (2) development of prespecified danger signs; (3) unexpected visits to the CHW; (4) hospitalizations; (5) deaths; (6) lack of perceived improvement per the child's caregiver on day 7; and (7) clinical failure, a composite outcome of persistence of fever on day 7, development of danger signs, hospitalization, or death. The 65 participating CHW enrolled 1,280 children, 1,220 (95.3%) of whom had sufficient data. Approximately 48% (587/1,220) and 52% (633/1,220) were enrolled during control (iCCM SCJA) and intervention periods (STAR SCJA), respectively. The observed percentage of children who were given or prescribed antibiotics at the initial visit was 91.8% (539/587) in the control periods as compared to 70.8% (448/633) during the intervention periods (adjusted prevalence difference -24.6%, 95% CI: -36.1%, -13.1%). The odds of antibiotic prescription by the CHW were over 80% lower in the intervention as compared to the control periods (OR 0.18, 95% CI: 0.06, 0.49). The frequency of clinical failure (iCCM SCJA 3.9% (23/585) v. STAR SCJA 1.8% (11/630); OR 0.41, 95% CI: 0.09, 1.83) and lack of perceived improvement by the caregiver (iCCM SCJA 2.1% (12/584) v. STAR SCJA 3.5% (22/627); OR 1.49, 95% CI: 0.37, 6.52) was similar. There were no unexpected visits or deaths in either group within the follow-up period. Incorporating CRP measurement into iCCM algorithms for evaluation of children with febrile ARI by CHW in rural Uganda decreased antibiotic use. There is evidence that this decrease was not associated with worse clinical outcomes, although the number of adverse events was low. These findings support expanded access to simple, point-of-care diagnostics to improve antibiotic stewardship in rural, resource-constrained settings where individuals with limited medical training provide a substantial proportion of care. ClinicalTrials.gov NCT05294510. The study was reviewed and approved by the University of North Carolina Institutional Review Board (#18-2803), Mbarara University of Science and Technology Research Ethics Committee (14/03-19), and Uganda National Council on Science and Technology (HS 2631).

Background In many resource-constrained settings, community health workers (CHW) often provide the initial care for children under five years of age. As part of integrated community case management (iCCM) programs, CHW frequently diagnose and treat acute respiratory illness (ARI), a leading cause of pediatric mortality and indication for antibiotic use globally. Yet knowledge and perceptions of antibiotic prescribing for ARI among CHW are not well-studied. The goal of this study was to assess knowledge, attitudes, and practices related to antibiotics among CHW implementing a stepped-wedge trial of an enhanced iCCM algorithm for children with ARI in rural Uganda to inform future antimicrobial stewardship strategies. Methods We conducted a nested mixed methods study with a convergent parallel design, administering surveys before and after the stepped wedge trial and individual semi-structured interviews at study end. We employed descriptive statistics, Wilcoxan rank sum tests, and thematic content analysis methods. Results A total of 63 of 67 (94.0%) CHW completed both baseline and follow-up surveys, and 15 CHW were interviewed. The median age of the full cohort was 40 (IQR: 35–47) years with 9.5 years of CHW experience (IQR: 4.0–14.0 years). Almost all CHW (95.2%) identified amoxicillin as an antibiotic at baseline, and most associated antibiotics with treating bacterial diseases (baseline: 82.5%, follow-up: 93.7%, p  = 0.05). Most perceived antibiotics as harmful to patients when prescribed unnecessarily. At follow-up, more CHW disagreed that antibiotics should be prescribed when in doubt. They welcomed additional education about antimicrobial resistance and diagnostic tools to advance antimicrobial stewardship (AMS). Conclusion CHW were overall familiar with antibiotics and their potential harms. They were eager to gain knowledge regarding AMS and AMR and share it with their communities. CHW represent an underutilized resource for AMS interventions and should be included in their design and implementation.

The Mbarara University of Science and Technology (MUST)'s First Mile Community Health Program (FMCH) has facilitated community placement of clinical residents at Primary Healthcare (PHC) facilities within the MUST catchment area in southwestern Uganda. While community-based training of medical residents is common in sub-Saharan Africa, little is known about how PHC facility leaders perceive its effect on service delivery in Uganda. This assessment aimed to describe the perspectives of PHC facility leaders on the impact of clinical residents' community placements on PHC services in southwestern Uganda between 2018 and 2023. From July 2018 to December 2023, 152 clinical residents from ten specialties were placed at PHC facilities in southwestern Uganda. This was a cross-sectional study based on qualitative data-collection techniques. This study focused on MUST clinical residents and PHC facilities in the MUST catchment in southwestern Uganda. We conducted KIIs with 15 health facility leaders until no new ideas emerged. Data were deductively analyzed using WHO's five strategic directions. Transcripts were transcribed verbatim, repeatedly reviewed, and coded into predefined categories. Interviewers bracketed their own experiences to ensure facility leaders' perspectives were accurately captured. Of the 15 facility leaders interviewed, most were male and from government HC IVs. Leaders reported that resident placements improved health service delivery through community engagement, enhancing care models through training, mentorship and low-cost innovations, and improving service coordination, including establishing specialized clinics and promoting better use of equipment. Residents also supported advocacy and resource mobilization. However, short placements, inconsistent outreach, staff shortages and lack of specialists limited continuity and sustainability. Facility leaders reported perceived improvement in strengthening PHC services by the clinical residents. Sustaining these gains will require institutionalized partnerships and evaluation of long-term impact. This could contribute to the advancement of primary healthcare services.

Women 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. Baseline 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. Of 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. Study 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 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

Youth 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. The 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. Study 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.

Women engaged in sex work (WESW) in Uganda face a high risk of HIV and other sexually transmitted infections (STIs), driven by the intersection of gender inequality, poverty and structural barriers. This paper reports on the Kyaterekera Project, a cluster-randomized controlled trial (c-RCT) testing the efficacy of a combined HIV risk reduction (HIVRR) and economic empowerment intervention to reduce biologically confirmed STIs and HIV risk behaviours. The study recruited 542 WESW from 19 HIV hotspots across four districts in Uganda between June 2019 and March 2020. Participants were randomized into three groups: (1) HIVRR intervention alone; (2) HIVRR combined with financial literacy training and an unconditional matched savings account; or (3) HIVRR combined with financial literacy training and an unconditional matched savings account and vocational training. Although initially implemented as a three-arm c-RCT, the COVID-19 lockdown prevented the implementation of the vocational training component. Therefore, the two treatment groups were combined, and the trial was re-approved as a two-arm c-RCT. Biological assessments were conducted at baseline, 18 and 24 months. Behavioural assessments were conducted at baseline, 6, 12, 18 and 24 months from April 2019 to December 2023. Primary outcomes included incident HIV acquisitions (seroconversions among baseline HIV-negative participants), point prevalence of STIs at each visit, and the number/proportion of unprotected sexual acts with paying and regular partners. This study utilized community-based participatory research methods, engaging a community advisory board to ensure the study's alignment with local needs. Across follow-up, condomless sex with paying partners decreased and income shifted towards non-sex work in both arms; no between-group differences were detected. Eighteen incident HIV acquisitions occurred (14 by 18 months; 4 additional by 24 months) with no between-group differences. STI prevalence was lower at 18 months compared to baseline, but not sustained at 24 months. In an environment of high baseline HIV prevalence, substantial pre-exposure prophylaxis uptake and COVID-19 disruptions, the added financial literacy/savings components did not yield measurable incremental benefits over HIVRR alone. Integrating an unconditional matched-savings model within an HIVRR platform was feasible. NCT03583541.

Introduction Optimal antiretroviral therapy (ART) adherence is crucial for improved patient outcomes; however, ART adherence among adolescents living with HIV (ALHIV) is low. Also, the performance of various adherence measures among ALHIV is under contention. We monitored ART adherence and compared Self‐report (SR) and Wisepill electronic monitoring (EM) performance in measuring ART adherence and predicting HIV viral suppression among ALHIV. Methods Between January 2014 and December 2015, we recruited 702 ALHIV aged 10–16 years into our cluster‐randomized controlled trial (2012–2018) in 39 clinics in Uganda. The intervention included a long‐term savings child development account, four micro‐enterprise workshops and 12 mentorship sessions. Using the entire sample, we performed multilevel logistic regression to predict monthly ART adherence trends for the first year of follow‐up. Since it is possible that the intervention had different effects on SR and EM adherence, we used participants in the control arm only to compare adherence using SR and EM and to calculate their sensitivity and specificity in predicting viral suppression. Results There was a significant decline in adherence for each month throughout the entire follow‐up period regardless of the group assigned. Good ART adherence was measured at 79.2% (75.2–82.6%) and 97.0% (95.4–98.1%) using EM and SR, respectively. Overall, 64.3% (60.6–67.9%) had suppressed viral loads. The specificities for EM and SR in predicting viral non‐suppression were 80.4% (73.6–85.7%) and 96.7% (93.3–98.4%), while the sensitivities were 22.9% (15.0–33.3%) and 1.8% (0.4–6.9%), respectively. The area under the curve was low for both EM and SR, at 53.6% (45.7–61.5%) and 56.2% (53.2–59.3%), respectively. There was high agreement (78%) between SR and EM in monitoring adherence. Conclusions Our findings highlighted the need for strategies for sustained optimal adherence. SR and EM measure adherence with a considerable agreement; however, neither is an accurate predictor of virological outcome. There is still a need for an acceptable, feasible and affordable method that predicts viral suppression among ALHIV.

Introduction Evidence from low‐resource settings indicates that economic insecurity is a major barrier to HIV treatment adherence. Economic empowerment (EE) interventions have the potential to improve adherence outcomes among adolescents living with HIV (ALWHIV) by mitigating the effects of poverty. This study aims to assess the efficacy and cost‐effectiveness of a savings‐led family‐based EE intervention, Suubi + Adherence, aimed at improving antiretroviral therapy (ART) adherence outcomes ALWHIV in Uganda. Methods Adolescents (mean age 12 years at enrolment; 56% female) receiving ART for HIV at 39 health centres were randomized to Suubi + Adherence intervention (n = 358) or bolstered standard of care (BSOC; n = 344). A difference‐in‐differences analysis was employed to assess the change in the proportion of virally suppressed adolescents (HIV RNA viral load <40 copies/mL) over 24 months. The cost‐effectiveness analysis examined how much the intervention cost to virally suppress one additional adolescent relative to BSOC from the healthcare provider perspective. Results At 24 months, the intervention was associated with an 8.85‐percentage point [95% confidence interval (CI) 0.80 to 16.90 percentage points] increase in the proportion of virally suppressed adolescents between the study arms (p = 0.032). Per‐participant costs were US $177 and US$ 263 for the BSOC and intervention groups respectively. The incremental cost of virally suppressing one additional adolescent was estimated at US $970 [95% CI, US$ 508 to 10,725] over two years. Conclusions Our results support the integration of family‐based EE interventions into adherence‐support strategies as part of routine HIV care in low‐resource settings to address the underlying economic drivers of poor ART adherence among ALWHIV. Moreover, per‐participant costs to achieve viral suppression do not seem prohibitive compared to other community‐based adherence interventions targeted at ALWHIV in low‐resource settings. Further research on combination interventions at the nexus of economic security and HIV treatment and care is needed to inform the development of feasible and scalable HIV policies and programmes.

This study examined the feasibility and acceptability of two group-based interventions: group-cognitive behavioral therapy (G-CBT) and a family-strengthening intervention delivered via multiple family group (MFG-FS), to address HIV stigma among adolescents living with HIV (ALHIV) and their caregivers. A total of 147 adolescent -caregiver dyads from 9 health clinics situated within 7 political districts in Uganda were screened for eligibility. Of these, 89 dyads met the inclusion criteria and provided consent to participate in the study. Participants were randomized, at the clinic level, to one of three study conditions: Usual care, G-CBT or MFG-FS. The interventions were delivered over a 3-month period. While both adolescents and their caregivers attended the MFG-FS sessions, G-CBT sessions were only attended by adolescents. Data were collected at baseline, 3 and 6-months post intervention initiation. The retention rate was 94% over the study period. Across groups, intervention session attendance ranged between 85 and 92%, for all sessions. Fidelity of the intervention was between 85 and 100%, and both children and caregivers rated highly their satisfaction with the intervention sessions. ALHIV in Uganda, and most of sub–Saharan Africa, are still underrepresented in stigma reduction interventions. The Suubi4Stigma study was feasible and acceptable to adolescents and their caregivers –supporting testing the efficacy of the interventions in a larger trial.