Incidence of Health Facility Switching and Associations With HIV Viral Rebound Among Persons on Antiretroviral Therapy in Uganda: A Population-based Study.

BACKGROUND: A substantial proportion of persons on antiretroviral therapy (ART) considered lost to follow-up have actually transferred their human immunodeficiency virus (HIV) care to other facilities. However, the relationship between facility switching and virologic outcomes, including viral rebound, is poorly understood. METHODS: We used data from 40 communities (2015-2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. Persons aged 15-49 years with serologically confirmed HIV who self-reported ART use and contributed ≥1 follow-up visit were included. Facility switching and virologic outcomes were assessed between 2 consecutive study visits (ie, index and follow-up visits, interval of approximately 18 months). Those who reported different HIV treatment facilities between index and follow-up study visits were classified as having switched facilities. Virologic outcomes included viral rebound among individuals initially suppressed (<200 copies/mL). Multivariable Poisson regression was used to estimate associations between facility switching and viral rebound. RESULTS: Overall, 2257 persons who self-reported ART use (median age, 35 years; 65% female, 92% initially suppressed) contributed 3335 visit-pairs and 5959 person-years to the analysis. Facility switching was common (4.8 per 100 person-years; 95% confidence interval [CI], 4.2-5.5) and most pronounced in persons aged <30 years and fishing community residents. Among persons suppressed at their index visit (n = 2076), incidence of viral rebound was more than twice as high in persons who switched facilities (adjusted incidence rate ratio = 2.27; 95% CI, 1.16-4.45). CONCLUSIONS: Facility switching was common and associated with viral rebound among persons initially suppressed. Investments in more agile, person-centered models for mobile clients are needed to address system inefficiencies and bottlenecks that can disrupt HIV care continuity.

Effectiveness of intensive adherence counselling in achieving an undetectable viral load among people on antiretroviral therapy with low-level viraemia in Uganda.

INTRODUCTION: Uganda was using a threshold of 1000 copies/mL to determine viral non-suppression for antiretroviral therapy monitoring among people living with HIV, prior to this study. It was not clear whether people living with HIV with low-level viraemia (LLV, ≥50 to <1000 copies/mL) would benefit from intensive adherence counselling (IAC). The purpose of this study was to determine the effectiveness of IAC among people living with HIV, receiving antiretroviral therapy, and with LLV in Uganda, to guide key policy decisions in HIV care, including the review of the viral load (VL) testing algorithm. METHODS: This cluster-randomized clinical trial comprised adults from eight HIV clinics who were living with HIV, receiving ART, and had recent VL results indicating LLV (tested from July 2022 to October 2022). Participants in the intervention arm clinics received three once-monthly sessions of IAC, and those in the comparison non-intervention arm clinics received the standard of care. At the end of the study, all participants were re-tested for VL to determine the proportions of those who then had an undetectable VL (<50 copies/mL). We assessed the statistical association between cross-tabulated variables using Fisher's exact test and then modified Poisson regression. RESULTS: A total of 136 participants were enrolled into the study at eight HIV clinics. All 68 participants in the intervention arm completed all IAC sessions. Only one participant in the non-intervention arm was lost to follow-up. The average follow-up time was 3.7 months (standard deviation [SD] 0.2) and 3.5 months (SD 0.1) in the intervention and non-intervention arms, respectively. In total, 59 (43.7%) of 135 people living with HIV achieved an undetectable VL during the study follow-up period. The effect of IAC on attaining an undetectable VL among people with LLV was nearly twice as high in the intervention arm (57.4%) than in the non-intervention arm (29.9%): adjusted risk ratio 1.9 (95% confidence interval 1.0-3.5), p = 0.037. CONCLUSION: IAC doubled the likelihood of an undetectable VL among people living with HIV with LLV. Therefore, IAC has been instituted as an intervention to manage people living with HIV with LLV in Uganda, and this should also be adopted in other Sub-Saharan African countries with similar settings. GOV IDENTIFIER: NCT05514418.

Motivational interviewing experiences from a community health worker-led HIV prevention and care intervention in rural Uganda: a qualitative study.

Motivational Interviewing (MI) and Community Health Workers (CHWs) are increasingly utilized in global settings to improve HIV outcomes, yet research exploring implementation strategies using MI and CHWs is lacking. We examined the experiences of CHWs and their clients in a counseling intervention which used MI-informed counseling to increase engagement in HIV prevention and treatment. This study was nested within the mLAKE cluster-randomized trial in a high HIV prevalence fishing community in rural Rakai District, Uganda. We conducted in-depth interviews with purposively-sampled CHWs (n = 8) and clients (n = 51). Transcripts were analyzed thematically to characterize CHWs' implementation of the intervention. Main themes identified included use of specific MI strategies (including evocation, guidance towards positive behavior change, active listening, and open-ended questions), and MI spirit (including collaboration, power-sharing, trust, and non-judgmental relationship building). Through these specific MI mechanisms, CHWs supported client behavior change to facilitate engagement with HIV services. This study provides evidence from a low-resource setting that CHWs with no previous experience in MI can successfully implement MI-informed counseling that is well-received by clients. CHW-led MI-informed counseling appears to be a feasible and effective approach to increase uptake of HIV prevention and care services in low-resource, HIV endemic regions.

Willingness to receive COVID-19 vaccines, associated factors and reasons for not taking a vaccine: a cross sectional study among persons aged 13-80 years in Wakiso, Central Uganda.

BACKGROUND: Vaccination has been recommended as one of the approaches for the control of COVID-19 pandemic. However, adequate vaccine coverage is critical to the effectiveness of the vaccine at population level. Data on acceptability of the vaccine in Ugandan urban areas are limited. This study examined the prevalence, factors associated with willingness to accept COVID-19 vaccine including reasons for not taking COVID-19 vaccine in a predominantly urban population of Wakiso, central Uganda. METHODS: Data were obtained from a cross-sectional study conducted between March 1st, 2021 and September 30th, 2021 in the urban population-based cohort of the Africa Medical and behavioral Sciences Organization (AMBSO). A Multivariable modified Poisson regression analysis was used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals of willingness to accept the COVID-19 vaccine. RESULTS: A total of 1,903 participants were enrolled in this study; 61% of whom were females. About 63% of participants indicated their willingness to accept the COVID-19 vaccine. Persons aged 13-19 years (aPR = 0.79; [95% CI: 0.74, 0.84]) or 20-29years (aPR = 0.93; [95% CI: 0.88, 0.98]) were less likely to accept the vaccine compared to persons aged 40-49 years. Persons with post-primary level of education (aPR = 1.05; [95% CI: 1.02, 1.09]) were more likely to accept the vaccine compared to persons with primary level of education. Additionally, students or individuals working in government (aPR = 1.13; [95% CI: 1.04, 1.23]) were more likely to accept the vaccine compared to individuals doing construction and Mechanic work as their main occupation. Reported reasons for not taking a COVID-19 vaccine included; concerns about side effects of the vaccine 154(57.0%), 64(23.7%) did not think the vaccines were effective, while 32(11.9%) did not like the vaccines. CONCLUSION: A substantial proportion of individuals were not willing to accept the COVID-19 vaccine. Health education campaigns on vaccination within urban communities could help reduce COVID-19 vaccine misconceptions in the urban populations more especially the young and persons with low levels of formal education.

The potential promise and pitfalls of point-of-care viral load monitoring to expedite HIV treatment decision-making in rural Uganda: a qualitative study.

BACKGROUND: HIV treatment programs in Africa have implemented centralized testing for routine viral load monitoring (VLM), which may result in specimen processing delays inhibiting timely return of viral load results. Decentralized, point-of-care (PoC) VLM is a promising tool for expediting HIV clinical decision-making but remains unavailable in most African settings. We qualitatively explored the perceived feasibility and appropriateness of PoC VLM to address gaps along the viral load monitoring continuum in rural Uganda. METHODS: Between May and September 2022, we conducted 15 in-depth interviews with HIV clinicians (facility in-charges, clinical officers, nurses, counselors) and six focus group discussions with 47 peer health workers from three south-central Ugandan districts. Topics explored centralized VLM implementation and opportunities/challenges to optimizing routine VLM implementation with PoC testing platforms. We explored perspectives on PoC VLM suitability and feasibility using iterative thematic analysis. Applying the Framework Method, we then mapped salient constraints and enablers of PoC VLM to constructs from the Consolidated Framework for Implementation Research. RESULTS: Clinicians and peers alike emphasized centralized viral load monitoring's resource-intensiveness and susceptibility to procedural/infrastructural bottlenecks (e.g., supply stockouts, testing backlogs, community tracing of clients with delayed VLM results), inhibiting timely clinical decision-making. Participants reacted enthusiastically to the prospect of PoC VLM, anticipating accelerated turnarounds in specimen processing, shorter and/or fewer client encounters with treatment services, and streamlined efficiencies in HIV care provision (including expedited VLM-driven clinical decision-making). Anticipated constraints to PoC VLM implementation included human resource requirements for processing large quantities of specimens (especially when machinery require repair), procurement and maintenance costs, training needs in the existing health workforce for operating point-of-care technology, and insufficient space in lower-tier health facilities to accommodate installation of new laboratory equipment. CONCLUSIONS: Anticipated implementation challenges, primarily clustering around resource requirements, did not diminish enthusiasm for PoC VLM monitoring among rural Ugandan clinicians and peer health workers, who perceived PoC platforms as potential solutions to existing inefficiencies within the centralized VLM ecosystem. Prioritizing PoC VLM rollout in facilities with available resources for optimal implementation (e.g., adequate physical and fiscal infrastructure, capacity to manage high specimen volumes) could help overcome anticipated barriers to decentralizing viral load monitoring.

The longitudinal impact of an evidence-based multiple family group intervention (Amaka Amasanyufu) on family cohesion among children in Uganda: Analysis of the cluster randomized SMART Africa-Uganda scale-up study (2016-2022).

Family functioning plays a critical role in childhood disruptive behavior disorders (The Family Journal, 2003, 11(1), 33-41; Research in Nursing and Health, 2016, 39(4), 229-243). Yet, there is limited research on the impact of evidence-based family strengthening interventions on improving family cohesion as a protective factor among children experiencing behavioral challenges. To address this gap, we analyzed data (N = 636) from the SMART Africa-Uganda study (2016-2022), a cluster randomized clinical trial testing an evidence-based family-strengthening intervention called Amaka Amasanyufu (translated as "Happy Families" in the local language). Children aged 8-13 and their caregivers were recruited from 26 public primary schools that were randomized to: (1) control condition receiving generalized psychosocial literature (10 schools), (2) intervention delivered via parent peers (eight schools), and (3) intervention delivered via community healthcare workers (eight schools). Children completed the family cohesion questionnaire at baseline, 8 weeks, 16 weeks, and 6 months post-intervention completion. The intervention effectiveness was evaluated via a three-level logistic mixed effects model with pairwise comparisons across study conditions within each time point. Participants in the parent-peer intervention group had greater odds of being in the higher family cohesion group than participants in the control group at 8 weeks (OR = 3.24), 16 weeks (OR = 1.88) and 6 months (OR = 2.07). At 8 weeks, 16 weeks, and 6 months, participants in the community health worker group had 3.98, 2.08, and 1.79 times greater odds of being in the higher family cohesion group than participants in the control group, respectively. Our findings strengthen the evidence base for Amaka Amansayufu as an effective intervention that can be utilized in SSA to improve family cohesion in families with children experiencing behavioral challenges.

The Long-term (5-year) Impact of a Family Economic Empowerment Intervention on Adolescents Living with HIV in Uganda: Analysis of Longitudinal Data from a Cluster Randomized Controlled Trial from the Suubi+Adherence Study (2012-2018).

150/150 words.We examined the 5-year impact of an economic empowerment (EE) intervention on: adherence, viral suppression, sexual risk-taking intentions (primary); and physical health, educational and economic (secondary) outcomes among adolescents living with HIV in Uganda. The Suubi + Adherence study (2012-2018) randomized clinics to: (1) Control group, n = 19 clinics, n = 344 participants; (2) intervention group which received matched savings accounts, mentorship, financial management and, business development training, n = 20 clinics, n = 358 participants. Participants completed post-baseline assessments at 12-, 24-, 36-, and 48-months. No significant differences in viral load, sexual risk-intentions and physical health perception were observed. The intervention group had better adherence (at 24-months) (Contrast=-0.28; 95% CI: -0.55, -0.004), higher school enrolment (OR = 2.18; 95% CI:1.30, 3.66); reported savings OR = 2.03 (1.29, 3.18) and higher savings (Contrast = 0.40; 95% CI:0.10, 0.70) than controls at 48-months. The EE intervention was efficacious in improving adherence, school enrolment, and economic outcomes creating opportunities for improved overall health among adolescents living with HIV.

Severe Acute Respiratory Syndrome Coronavirus-2 seroprevalence in South-Central Uganda, during 2019-2021.

BACKGROUND: Globally, key subpopulations such as healthcare workers (HCW) may have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to Personal Protective Equipment and lack of clarity on the extent/pattern of community spread may exacerbate this situation. The country established infection prevention/control measures such as lockdowns and proper hand hygiene. However, due to resource limitations and fatigue, compliance is low, posing continued onward transmission risk. This study aimed to describe extent of SARS-CoV-2 seroprevalence in selected populations within the Rakai region of Uganda. METHODS: From 30th November 2020 to 8th January 2021, we collected venous blood from 753 HCW at twenty-six health facilities in South-Central Uganda and from 227 population-cohort participants who reported specific COVID-19 like symptoms (fever, cough, loss of taste and appetite) in a prior phone-based survey conducted (between May and August 2020) during the first national lockdown. 636 plasma specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda were also retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek™ rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Overall seroprevalence in each participant group was estimated, adjusting for test performance. RESULTS: The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% [95%CI: 23.5, 29.8] with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the phone-based survey participants, 15.6% [95%CI: 10.9, 20.3] had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% [95%CI: 1.2, 3.5] were reactive. CONCLUSIONS: Findings suggest high seroprevalence of antibodies to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether seroprevalence among plasma specimens collected prior to confirmation of the first COVID-19 case implies prior SARS-CoV-2 exposure in Uganda.

Prevalence and Predictors of Persistent Human Immunodeficiency Virus Viremia and Viral Rebound After Universal Test and Treat: A Population-Based Study.

BACKGROUND: There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa. METHODS: Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression. RESULTS: There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15-29 vs 40-49 years; adjRR = 1.80; 95% CI = 1.19-2.71), male sex (adjRR = 2.09, 95% CI = 1.47-2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34-2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34-2.73) were factors associated with persistent viremia. CONCLUSIONS: Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.

Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda.

BACKGROUND: The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. METHODS: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men. RESULTS: A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21-35 years) to 22 years (IQR, 18-29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28-.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. CONCLUSIONS: VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

Novel community health worker strategy for HIV service engagement in a hyperendemic community in Rakai, Uganda: A pragmatic, cluster-randomized trial.

BACKGROUND: Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called "Health Scouts" to promote engagement in HIV treatment and prevention services. METHODS AND FINDINGS: The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV-positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV-positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect. CONCLUSIONS: A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02556957.

Assessment, prevalence, and correlates of frailty among middle-aged adults with HIV in rural Uganda.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

Improvement in depressive symptoms after antiretroviral therapy initiation in people with HIV in Rakai, Uganda.

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies-Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P's < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aß-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences.

Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda.

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1ß, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies.

Prediction-driven pooled testing methods: Application to HIV treatment monitoring in Rakai, Uganda.

Chronic medical conditions often necessitate regular testing for proper treatment. Regular testing of all afflicted individuals may not be feasible due to limited resources, as is true with HIV monitoring in resource-limited settings. Pooled testing methods have been developed in order to allow regular testing for all while reducing resource burden. However, the most commonly used methods do not make use of covariate information predictive of treatment failure, which could improve performance. We propose and evaluate four prediction-driven pooled testing methods that incorporate covariate information to improve pooled testing performance. We then compare these methods in the HIV treatment management setting to current methods with respect to testing efficiency, sensitivity, and number of testing rounds using simulated data and data collected in Rakai, Uganda. Results show that the prediction-driven methods increase efficiency by up to 20% compared with current methods while maintaining equivalent sensitivity and reducing number of testing rounds by up to 70%. When predictions were incorrect, the performance of prediction-based matrix methods remained robust. The best performing method using our motivating data from Rakai was a prediction-driven hybrid method, maintaining sensitivity over 96% and efficiency over 75% in likely scenarios. If these methods perform similarly in the field, they may contribute to improving mortality and reducing transmission in resource-limited settings. Although we evaluate our proposed pooling methods in the HIV treatment setting, they can be applied to any setting that necessitates testing of a quantitative biomarker for a threshold-based decision.

Transactional Sex, Alcohol Use and Intimate Partner Violence Against Women in the Rakai Region of Uganda.

Transactional sex (TS) is prevalent in sub-Saharan Africa. Women's engagement in TS is linked with HIV infection; little is known about the relationship between TS, intimate partner violence (IPV) and alcohol use-established HIV risk behaviors. Using modified Poisson regression, we assessed associations between TS and physical, verbal and sexual IPV among 8248 women (15-49 years) who participated in the Rakai Community Cohort Study across forty communities in Uganda. An interaction term assessed moderation between alcohol use and TS and no significant interaction effects were found. In adjusted analysis, alcohol use and TS were significantly associated with all forms of IPV. In stratified analysis, TS was only associated with IPV in agrarian communities; alcohol use was not associated with physical IPV in trade communities or sexual IPV in trade and fishing communities. Identifying differences in IPV risk factors by community type is critical for the development of tailored interventions.

RESUMEN: El sexo transaccional (ST) es frecuente en África subsahariana. La participación de las mujeres en el ST está relacionada con la infección por VIH; Se sabe poco sobre la relación entre el ST, la violencia de pareja íntima (VPI) y el consumo de alcohol: conductas de riesgo establecidas para el VIH. Utilizando la regresión de Poisson modificada, evaluamos las asociaciones entre el ST y la VPI física, verbal y sexual entre 8,248 mujeres (15-49 años) que participaron en el Estudio de cohorte de la comunidad Rakai en cuarenta comunidades de Uganda. Un término de interacción evaluó la moderación entre el consumo de alcohol y el ST y no se encontraron efectos de interacción significativos. En el análisis ajustado, el consumo de alcohol y el ST se asociaron significativamente con todas las formas de VPI. En el análisis estratificado, el ST solo se asoció con la VPI en las comunidades agrarias; El consumo de alcohol no se asoció con la VPI física en las comunidades comerciales ni con la VPI sexual en las comunidades comerciales y pesqueras. Identificar las diferencias en los factores de riesgo de la violencia de género por tipo de comunidad es fundamental para el desarrollo de intervenciones personalizadas.

Qualitative Assessment of Barriers and Facilitators of PrEP Use Before and After Rollout of a PrEP Program for Priority Populations in South-central Uganda.

Uganda piloted HIV pre-exposure prophylaxis (PrEP) for priority populations (sex workers, fishermen, truck drivers, discordant couples) in 2017. To assess facilitators and barriers to PrEP uptake and adherence, we explored perceptions of PrEP before and experiences after rollout among community members and providers in south-central Uganda. We conducted 75 in-depth interviews and 12 focus group discussions. We analyzed transcripts using a team-based thematic framework approach. Partners, family, peers, and experienced PrEP users provided adherence support. Occupational factors hindered adherence for sex workers and fishermen, particularly related to mobility. Pre-rollout concerns about unskilled/untrained volunteers distributing PrEP and price-gouging were mitigated. After rollout, awareness of high community HIV risk and trust in PrEP effectiveness facilitated uptake. PrEP stigma and unexpected migration persisted as barriers. Community-initiated, tailored communication with successful PrEP users may optimize future engagement by addressing fears and rumors, while flexible delivery and refill models may facilitate PrEP continuation and adherence.

RESUMEN: En 2017, Uganda introdujo profilaxis pre-exposición (PrEP), dirigida a las populaciones con alto riesgo de contraer al VIH (trabajadoras sexuales, pescadores, camioneros, parejas sero-discordantes). Para investigar facilitadores y barreras para la adopción y la adherencia a la PrEP, exploramos percepciones de PrEP antes y después de su introducción en Uganda. Realizamos 75 entrevistas y 12 grupos focales con miembros de la comunidad y trabajadores de salud. Analizamos las transcripciones temáticamente usando un marco de referencia. Parejas, familias, compañeros, y clientes usando PrEP apoyaron a los demás mantener adherencia. Movilidad fue una barrera para la adherencia a la PrEP para trabajadoras sexuales y pescadores. Preocupaciones sobre el entrenamiento de los distribuidores de PrEP y la especulación de precios no fueron realizadas. Percepciones del riesgo del VIH y confianza en la eficacia de PrEP facilitaron su adopción. Estigma y migración inesperada persistieron como barreras para la adopción de PrEP. Comunicaciones manejadas por clientes usando PrEP pueden motivar interés en PrEP y abordar rumores. Sistemas flexibles del entrego y la recarga de medicinas pueden permitir continuación de, y adherencia a, la PrEP.

Not Enough Money and Too Many Thoughts: Exploring Perceptions of Mental Health in Two Ugandan Districts Through the Mental Health Literacy Framework.

Mental health disorders account for a heavy disease burden in Uganda. In order to provide culturally appropriate mental health prevention and treatment approaches, it is necessary to understand how mental health is conceptualized in the population. Three focus group discussions (FGDs) and 31 in-depth interviews (IDIs) were conducted with men and women aged 14 to 62 years residing in rural, urban, and semi-urban low-income communities in central and western Uganda to explore perceptions and knowledge of mental health. Interpretive thematic analysis was undertaken; results were organized through the lens of the mental health literacy framework. Environmental and societal stressors were identified as primary underlying causes of poor mental health. While participants recognized symptoms of poor mental health, gaps in mental health literacy also emerged. Mental health resources are needed in this setting and additional qualitative work assessing knowledge and attitudes toward mental health care seeking behavior can inform the development of acceptable integrated services.

Impact of Universal Antiretroviral Treatment Eligibility on Rapid Treatment Initiation Among Young Adolescents with Human Immunodeficiency Virus in Sub-Saharan Africa.

BACKGROUND: Young adolescents with perinatally acquired human immunodeficiency virus (HIV) are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation after care enrollment among 10-14-year-olds in 7 sub-Saharan African countries. METHODS: Regression discontinuity analysis and data for 6912 patients aged 10-14-years were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) after adoption of Treat All policies in 2 groups of countries: Uganda and Zambia (policy adopted in 2013) and Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda (policy adopted in 2016). RESULTS: There were immediate increases in rapid ART initiation among young adolescents after national adoption of Treat All. Increases were greater in countries adopting the policy in 2016 than in those adopting it in 2013: 23.4 percentage points (pp) (95% confidence interval, 13.9-32.8) versus 11.2pp (2.5-19.9). However, the rate of increase in rapid ART initiation among 10-14-year-olds rose appreciably in countries with earlier treatment expansions, from 1.5pp per year before Treat All to 7.7pp per year afterward. CONCLUSIONS: Universal ART eligibility has increased rapid treatment initiation among young adolescents enrolling in HIV care. Further research should assess their retention in care and viral suppression under Treat All.

Adaptive Viral Load Monitoring Frequency to Facilitate Differentiated Care: A Modeling Study From Rakai, Uganda.

BACKGROUND: After scale-up of antiretroviral therapy (ART), routine annual viral load monitoring has been adopted by most countries, but reduced frequency of viral load monitoring may offer cost savings in resource-limited settings. We investigated if viral load monitoring frequency could be reduced while maintaining detection of treatment failure. METHODS: The Rakai Health Sciences Program performed routine, biannual viral load monitoring on 2489 people living with human immunodeficiency virus (age ≥15 years). On the basis of these data, we built a 2-stage simulation model to compare different viral load monitoring schemes. We fit Weibull regression models for time to viral load >1000 copies/mL (treatment failure), and simulated data for 10 000 individuals over 5 years to compare 5 monitoring schemes to the current viral load testing every 6 months and every 12 months. RESULTS: Among 7 monitoring schemes tested, monitoring every 6 months for all subjects had the fewest months of undetected failure but also had the highest number of viral load tests. Adaptive schemes using previous viral load measurements to inform future monitoring significantly decreased the number of viral load tests without markedly increasing the number of months of undetected failure. The best adaptive monitoring scheme resulted in a 67% reduction in viral load measurements, while increasing the months of undetected failure by <20%. CONCLUSIONS: Adaptive viral load monitoring based on previous viral load measurements may be optimal for maintaining patient care while reducing costs, allowing more patients to be treated and monitored. Future empirical studies to evaluate differentiated monitoring are warranted.