Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies.

BACKGROUND: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. METHODS AND FINDINGS: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. CONCLUSIONS: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.

Effects of Maternal HIV Infection and Alcohol Use in Pregnancy on Birth Outcomes in Uganda.

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (ß = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (ß = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.

Acceptability, feasibility and preliminary effectiveness of the mHealth intervention, InTSHA, on retention in care and viral suppression among adolescents with HIV in South Africa: a pilot randomized clinical trial.

We describe the results of a pilot randomized clinical trial of a mobile phone-based intervention, InTSHA: Interactive Transition Support for Adolescents with HIV, compared to standard care. Encrypted, closed group chats delivered via WhatsApp provided peer support and improved communication between adolescents with HIV, their caregivers, and healthcare providers. We randomized 80 South African adolescents ages 15 to 19 years with perinatally-acquired HIV to receive either the intervention (n=40) or standard of care (n=40). We measured acceptability (Acceptability of Intervention Measure [AIM]) and feasibility (Feasibility of Intervention Measure [FIM]) as primary outcomes. We evaluated impact on retention in care and viral suppression six months after randomization as secondary endpoints. We performed bivariable and multivariable analyses using logistic regression models to assess the effect of the InTSHA intervention compared to standard of care. Among the adolescents randomized to the InTSHA intervention, the median AIM was 4.1/5.0 (82%) and median FIM was 3.9/5.0 (78%). We found no difference in retention in care or in viral suppression comparing intervention and control groups. Among adolescents who attended three or more sessions, retention in care was 100% at 6 months. InTSHA is an acceptable and feasible mHealth intervention warranting further study in a larger population.

Negative clinic experiences as a barrier to care for people with HIV and their impact on patient preferences for intervention support: a qualitative study in Cape Town, South Africa.

We conducted qualitative research among people with HIV (PWH) and care providers in Cape Town, South Africa to understand the impact of negative clinic experiences on adherence and support preferences. In-depth interviews were conducted with 41 patients with an unsuppressed viral load or a treatment gap, and focus group discussions with physicians, nurses, counselors, and community health workers. Questions addressed treatment history and adherence barriers, then participants evaluated evidence-based adherence interventions for potential scale up. Inductive analysis examined care experiences and corresponding preference for intervention options. More than half of PWH described negative experiences during clinic visits, including mistreatment by staff and clinic administration issues, and these statements were corroborated by providers. Those with negative experiences in care stated that fear of mistreatment led to nonadherence. Most patients with negative experiences preferred peer support groups or check-in texts to clinic-based interventions. We found that PWH's negative clinic experiences were a primary reason behind nonadherence and influenced preferences for support mechanisms. These findings emphasize the importance of HIV treatment adherence interventions at multiple levels both in and outside of the clinic, and providing more comprehensive training to providers to better serve PWH in adherence counseling, especially those who are most vulnerable..

High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda: A cohort study.

BACKGROUND: In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. METHODS AND FINDINGS: We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure ("high" adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as "high." Women who became pregnant were initially exited from the cohort by design; from March 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group. CONCLUSIONS: Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03832530 https://clinicaltrials.gov/ct2/show/NCT03832530?term=lynn+matthews&cond=hiv&cntry=UG&draw=2&rank=1.

Multicenter Analysis of Attrition from the Pediatric Tuberculosis Infection Care Cascade in Boston.

OBJECTIVE: To characterize losses from the pediatric tuberculosis (TB) infection care cascade to identify ways to improve TB infection care delivery. STUDY DESIGN: We conducted a retrospective cohort study of children (age <18 years) screened for TB within 2 Boston-area health systems between January 2017 and May 2019. Patients who received a tuberculin skin test (TST) and/or an interferon gamma release assay (IGRA) were included. RESULTS: We included 13 353 tests among 11 622 patients; 93.9% of the tests were completed. Of 199 patients with positive tests for whom TB infection evaluation was clinically appropriate, 59.3% completed treatment or were recommended to not start treatment. Age 12-17 years (vs < 5 years; aOR 1.59; 95% CI, 1.32-1.92), non-English/non-Spanish language preference (vs English; aOR, 1.34; 95% CI, 1.02-1.76), and receipt of an IGRA (vs TST, aOR, 30.82; 95% CI, 21.92-43.34) were associated with increased odds of testing completion. Odds of testing completion decreased as census tract social vulnerability index quartile increased (ie, social vulnerability worsened; most vulnerable quartile vs least vulnerable quartile, aOR, 0.77; 95% CI, 0.60-0.99). Odds of completing treatment after starting treatment were higher in females (vs males; aOR, 2.35; 95% CI, 1.14-4.85) and were lower in patients starting treatment in a primary care clinic (vs TB/infectious diseases clinic; aOR, 0.44; 95% CI, 0.27-0.71). CONCLUSIONS: Among children with a high proportion of negative TB infection tests, completion of testing was high, but completion of evaluation and treatment was moderate. Transitions toward IGRA testing will improve testing completion; interventions addressing social determinants of health are important to improve treatment completion.

Sexually Transmitted Infection Point-of-Care Testing in Resource-Limited Settings: A Narrative Review Guided by an Implementation Framework.

ABSTRACT: Most sexually transmitted infections (STIs) are acquired in resource-limited settings (RLSs) where laboratory diagnostic access is limited. Advancements in point-of-care testing (POC) technology have the potential to bring STI testing to many RLSs. We define POC as performed near the patient and with results readily available to inform clinical practice. The World Health Organization Special Programme for Research and Training in Tropical Diseases further outlines desirable POC characteristics with the REASSURED criteria.Despite advantages related to immediate test-and-treat care, integrating POC into RLS health care systems can present challenges that preclude reliance on these tests. In 2018, we incorporated molecular near-POC for chlamydia, gonorrhea, and trichomoniasis and SDBioline treponemal immunochromatographic testing confirmed by rapid plasma reagin for syphilis diagnosis at the Mbarara University of Science and Technology Research Laboratory in rural southwestern Uganda. We describe our experiences with STI POC as a case example to guide a narrative review of the field using the Consolidated Framework for Implementation Research as a conceptual framework.Although POC and near-POC are described as easy to use, the challenges of limited person-power, health care processes, limited infrastructure/resources, high costs, and quality control obstacles can impede the impact of these tests. Increased investment in operators, training, and infrastructure, restructuring health care systems to accommodate increased POC access, and optimizing costs are all crucial to the successful implementation of STI POC in RLS. Expanded STI POC in RLS will increase access to accurate diagnoses, appropriate treatment, and engagement in partner notification, treatment, and prevention efforts.

Trajectories of Oral PrEP Adherence Among Young Kenyan Women: Implications for Promoting Effective PrEP Use.

Using data from a 2-year study of young women at high HIV risk in Thika and Kisumu, Kenya, we identified group-based trajectories of PrEP adherence based on electronic pillcap-monitoring and assessed potentially associated demographic and socio-behavioral factors. Among 348 women, we selected a three-trajectory adherence model: low and declining (N = 211, 61%), moderate but declining (N = 119, 34%) and steady high adherers (N = 18, 5%). We also identified a two-trajectory HIV risk model based on self-perceived risk in the past week: high and increasing (N = 28, 8%) and steady low (N = 320, 92%) risk. The Kisumu site was associated with the moderate but declining and steady high adherence trajectories, while increasing VOICE risk score was associated with the low and declining adherence trajectory. We found no association between the adherence and risk trajectories. Our findings suggest adherence support may need tailoring by setting. Early, sustained support may also help those at highest risk of non-adherence.

RESUMEN: Utilizando datos de un estudio de dos años de duración en mujeres jóvenes con alto riesgo de VIH en Thika y Kisumu, Kenia, identificamos trayectorias grupales de adherencia a la PrEP basadas en el monitoreo electrónico de pillcap y evaluamos los factores demográficos, sociales y de comportamiento potencialmente asociados con la adherencia. En un grupo de 348 mujeres, seleccionamos un modelo de adherencia de tres trayectorias: baja y decreciente (N = 211, 61%), moderada pero decreciente (N = 119, 34%) y altas constantes (N = 18, 5%). También identificamos un modelo de riesgo de VIH de dos trayectorias basado en el riesgo autopercibido en la última semana: riesgo alto y creciente (N = 28, 8%) y riesgo bajo constante (N = 320, 92%). El sitio de Kisumu estuvo asociado con las trayectorias de adherencia alta moderadas pero decrecientes y constantes, mientras que el aumento de la puntuación de riesgo de VOICE se asoció con la trayectoria de adherencia baja y decreciente. No se encontró asociación entre la adherencia y las trayectorias de riesgo. Nuestros hallazgos sugieren que el apoyo a la adherencia podría individualizarse de acuerdo con el entorno. El apoyo temprano y sostenido a la adherencia también puede ayudar a las personas con mayor riesgo de no adherencia.

Performance of Multiple Adherence Measures for pre-exposure Prophylaxis (PrEP) Among Young Women in Kenya.

Understanding PrEP adherence is key in the formulation of HIV prevention strategies; however, measurement of adherence can be challenging. We compared multiple adherence measures in a two-year study of young Kenyan women at high risk of HIV acquisition. Among 289 participants, concordance between electronic adherence monitoring (EAM) and tenofovir diphosphate (TFV-DP) in dried blood spots ranged from 57 to 72% depending on selected thresholds. Using area under the receiver operating curve, discrimination of quantifiable TFV-DP was high at 0.85 with EAM and low at 0.49-0.54 for multiple self-reported measures. Correlation between EAM and self-reported measures was low (r < 0.11) although correlation within self-reported measures was moderate (r > 0.69). These findings indicate that both TFV-DP and EAM are useful PrEP adherence tools. Adherence would benefit from better availability of less expensive versions of both measurement tools. Additionally, further research on TFV-DP thresholds is needed to inform interpretation and use in understanding PrEP adherence in this population.

RESUMEN: Comprender la adherencia a la PrEP es importante en la formulación de estrategias de prevención del VIH; sin embargo, la medición de la adherencia puede ser difícil. Comparamos múltiples medidas de adherencia en un estudio de dos años de mujeres jóvenes kenianas con alto riesgo de contraer el VIH. Entre 289 participantes, la concordancia entre la monitorización electrónica de la adherencia (EAM) y el tenofovir difosfato (TFV-DP) en las manchas de sangre seca varió del 57% al 72% dependiendo de los umbrales seleccionados. Utilizando el área bajo la curva operativa del receptor, la discriminación de TFV-DP cuantificable fue alta en 0.85 con EAM y baja en 0.49­0.54 para múltiples medidas autoinformadas. La correlación entre la EAM y las medidas autoinformadas fue baja (r < 0,11), aunque la correlación entre de las medidas autoinformadas fue moderada (r > 0,69). Estos resultados indican que tanto TFV-DP como EAM son herramientas útiles de adherencia a la PrEP. La adherencia se beneficiaría de una mejor disponibilidad de versiones menos costosas de ambas herramientas de medición. Además, se necesita más investigación sobre los umbrales TFV-DP para informar la interpretación y el uso en la comprensión de la adherencia a la PrEP en esta población.

"Yes, I'm reminded, but it doesn't mean I'm taking them": Experiences with Short Message Service Reminder Use in Real-time Monitoring of HIV PrEP among Young Women in Kenya.

Adherence to oral pre-exposure prophylaxis (PrEP) is challenging, and cellular technology offers a promising opportunity for support. However, a recent randomized controlled trial found that SMS reminders did not improve PrEP adherence. We used qualitative methods to explore the trial participants' experiences with the SMS intervention. We conducted serial in-depth interviews with 54 young Kenyan women, using inductive and deductive content analysis . Initially, SMS reminders were highly acceptable. Participants expressed enthusiasm with receiving the reminders because of the coded nature of the SMS reminders; they also helped in 'habit forming' with daily adherence. However, overtime, participants reported growing concerns about privacy, self-efficacy, and responsibility and SMS fatigue. Participants also reported other challenges, including phone loss, poor telephone network, and lack of electricity. Further research to explore if SMS reminders in alternative formats or with different frequency is needed, in addition to identification of alternate adherence support strategies.

Systematic Review of mHealth Interventions for Adolescent and Young Adult HIV Prevention and the Adolescent HIV Continuum of Care in Low to Middle Income Countries.

Adolescents and young adults (AYA) in low to middle income countries (LMIC) have poorer outcomes along each step in the HIV continuum of prevention and care compared to younger children or older adults. The use of mHealth technology provides a potentially promising implementation strategy for interventions to remedy these disparities. We therefore conducted a systematic review of the English literature and conference proceedings from January 1, 2000 to April 1, 2021 evaluating mHealth interventions targeting AYA along each step of the HIV continuum of care in LMIC. We identified 27 mHealth interventions across the HIV continuum, with no interventions addressing transition from pediatric to adult care. The majority of studies were single arm, uncontrolled or underpowered, with few randomized trials resulting in mixed and inconclusive outcomes. mHealth interventions have potential to remedy disparities along the HIV continuum of care for AYA in LMIC but larger, powered randomized trials are needed.

RESUMEN: Los adolescentes y adultos jóvenes (AYA) en países de ingresos bajos a medianos (LMIC) tienen peores resultados en cada paso del continuo de prevención y atención del VIH en comparación con los niños más pequeños o los adultos mayores. El uso de la tecnología mHealth proporciona una estrategia de implementación potencialmente prometedora para las intervenciones para remediar estas disparidades. Por lo tanto, realizamos una revisión sistemática de los resúmenes y artículos publicados en inglés desde el 1 de enero de 2000 hasta el 1 de abril de 2021 para evaluar las intervenciones de mHealth dirigidas a AYA a lo largo de cada paso del continuo de atención del VIH en LMIC. Identificamos 27 intervenciones de mHealth en todo el continuo del VIH, sin intervenciones que abordaran la transición de la atención pediátrica a la de adultos. La mayoría de los estudios fueron de un solo brazo, no controlados o con bajo poder estadístico, con pocos ensayos aleatorios que dieron resultados mixtos y no concluyentes. Las intervenciones de mHealth tienen el potencial de remediar las disparidades a lo largo de la continuidad de la atención del VIH para AYA en LMIC, pero se necesitan ensayos aleatorios más grandes y potentes.

Multi-level Factors Driving Pre-exposure Prophylaxis Non-initiation Among Young Women at High Risk for HIV in Kenya.

Few studies have focused on understanding pre-exposure prophylaxis (PrEP) non-initiation among young, high-risk women in sub-Saharan Africa. This study aimed to qualitatively explore why young women in Kenya at high-risk for HIV chose not to enroll in a PrEP adherence trial. We performed 40 semi-structured interviews with young high-risk women assessing concerns about PrEP and/or study participation. We also assessed community-level factors influencing decision-making around PrEP through 10 focus groups involving peers, young men, caregivers, and community leaders. Our qualitative data reflect the complexity of navigating barriers preventing PrEP initiation in settings where taking PrEP may be perceived as immoral behavior. Framed within the context of risk perception, the decision to start PrEP may run counter to the potential risk of losing support from one's community. Our findings suggest that approaches addressing social norms, while de-medicalizing HIV prevention services, are needed to further increase PrEP uptake among young Kenyan women.

Dual trajectories of antiretroviral therapy adherence and polypharmacy in women with HIV in the United States.

BACKGROUND: Polypharmacy, using five or more medications, may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to antiretroviral therapy (ART) and polypharmacy. METHODS: We included women with HIV (aged ≥ 18) enrolled in the Women's Interagency HIV Study in the United States from 2014 to 2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and the dual GBTM to identify the interrelationship between adherence and polypharmacy. RESULTS: Overall, 1,538 were eligible (median age of 49 years). GBTM analysis revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group. CONCLUSIONS: The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence.

A user-centred implementation strategy for tuberculosis contact investigation in Uganda: protocol for a stepped-wedge, cluster-randomised trial.

BACKGROUND: Tuberculosis(TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented. METHODS: We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including (1) a TB-education booklet, (2) a contact-identification algorithm, (3) an instructional sputum-collection video, and (4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including (1) collaborative improvement meetings, (2) regular audit-and-feedback reports, and (3) a digital group-chat application designed to develop a community of practice. Sites will cross-over from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB(#554), the Uganda National Council for Science and Technology(#HS1720ES), and the Yale Institutional Review Board(#2000023199) approved the study and waived informed consent for the main trial implementation-effectiveness outcomes. We will submit results for publication in peer-reviewed journals and disseminate findings to local policymakers and representatives of affected communities. DISCUSSION: This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden settings using contact investigation. It will also help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustaining evidence-based interventions in low-and-middle-income countries. TRIAL REGISTRATION: The trial was registered(ClinicalTrials.gov Identifier NCT05640648) on 16 November 2022, after the trial launch on 7 March 2022.

High residual inflammation despite HIV viral suppression: Lessons learned from real-time adherence monitoring among people with HIV in Africa.

BACKGROUND: Lower antiretroviral therapy (ART) adherence is associated with higher systemic inflammation in virally suppressed people with HIV (PWH); however, previous studies have mostly relied on subjective adherence measures and have not assessed this association by disease stage upon ART initiation. METHODS: In the Monitoring Early Treatment Adherence study, adherence was monitored electronically in real time among adult, treatment-naïve PWH in Uganda and South Africa who initiated tenofovir disoproxil fumarate/emtricitabine/efavirenz during early-stage (CD4 > 350 cells/µL) or late-stage (CD4 < 200 cells/µL) disease. Participants who achieved viral suppression (< 400 copies/mL) at 6 months and remained suppressed after 12 months were analysed. The association between average ART adherence and plasma concentrations of interleukin 6 (IL-6), soluble CD14 (sCD14) and D-dimer was evaluated using adjusted multivariable linear regression, stratified by disease stage. RESULTS: In all, 488 PWH (61% women, mean age 35 years) were included in the analysis. Median ART adherence overall was 87%. In adjusted models, every 10% increase in average adherence was associated with a 3.0% decrease in IL-6 [95% confidence interval (CI): -5.9 to -0.01, p = 0.05] at 12 months. This relationship was observed in PWH with both early-stage (5.9%, 95% CI: -10.1 to -1.6, p = 0.009) and late-stage disease (3.7%, 95% CI: -7.2 to -0.2, p = 0.039). No significant associations were found with sCD14 or D-dimer. CONCLUSIONS: Objective ART adherence measurement was inversely associated with systemic inflammation in PWH who achieved viral suppression after ART initiation in sub-Saharan Africa, with a greater association in those with early-stage HIV. This finding underscores the importance of ART adherence beyond establishing viral suppression.

Development of a transition readiness score for adolescents living with perinatally-acquired HIV and transitioning to adult care.

We created a transition readiness score for adolescents with perinatally-acquired HIV as they transition from pediatric to adult care. Of the 199 adolescents who transitioned to adult care, 84 (42%) had viral suppression (< 200 copies/ml) one year after transition. Adolescents on first-line ART, with documented HIV status disclosure, and higher rating on the HIV Adolescent Readiness to Transition Scale had significantly higher odds of viral suppression after transition. Conversely, females, those with older age at ART initiation, and those with prior alcohol use had significantly lower odds of viral suppression after transition. Using these data, we created a transition readiness score organized into low, intermediate, and high levels of transition readiness. This transition readiness score can be used to identify adolescents who are likely ready to transition to adult care and identify additional areas for intervention to improve the likelihood of successful transition for those with lower transition readiness scores.

Individual and structural-level Correlates of Pre-exposure Prophylaxis (PrEP) lifetime and current use in a nationwide sample of young sexual and gender minorities.

The objective of this analysis was to describe individual and structural-level factors associated with pre-exposure prophylaxis (PrEP) use among a sample of sexual and gender minorities (SGM) at risk for HIV recruited using limited interaction strategies. SGM (N = 3330), ages 15-34, without HIV enrolled in a nationwide limited interaction cohort study from 2017 to 2020. A baseline cross-sectional single-survey design examined individual and structural-level correlates of PrEP lifetime use and current use using logistic regression. PrEP lifetime use and current use were reported by 31.2% and 23.9%, respectively, of SGM with PrEP data (n = 3077). PrEP use outcomes (lifetime or current use) in cisgender MSM were associated with being over age 18, Black or other race, Hispanic/Latina/x/o ethnicity, being gay, being out to one's healthcare provider, having health insurance, being a college graduate, and having a greater number of PrEP peers. PrEP use outcomes (lifetime use or current use) in transgender/non-binary participants were associated with being over age 24, being Latinx, being transgender vs. non-binary, being assigned male at birth, being out to their healthcare provider, living in the western or northeastern United States, and having more peers on PrEP. More work is needed to address lower PrEP uptake in SGM under 18 and those whose sex risk may be more dynamic (e.g., non-binary, pansexual/queer, and bisexual SGM) and such strategies should consider utilizing peers to provide information and ameliorate structural barriers.

RESUMEN: Este análisis describe los determinantes sociales asociados con el uso de la PrEP entre una cohorte contemporánea de minorías sexuales y de género (MSG) en riesgo de contraer el VIH en los Estados Unidos. Los participantes incluyeron MSG (N = 3330), de 15 a 34 años, sin VIH reclutados por redes sociales entre 2017­2020. Usando los datos de inscripción, una regresión analizó la historia del uso de la PrEP. Los factores asociados con el uso de la PrEP entre este grupo indicaron que los mayores de edad, los abiertos sobre su sexualidad con sus médicos, y los que conocían compañeros que usaban la PrEP, todos eran más propensos a haber usado la PrEP. Más esfuerzo se requiere para abordar el uso de la PrEP entre aquellos cuyos su riesgo sexual puede ser más dinámico.

Understanding PrEP Acceptability Among Priority Populations: Results from a Qualitative Study of Potential Users in Central Uganda.

Daily oral pre-exposure prophylaxis (PrEP) can safely and effectively prevent HIV acquisition in HIV-negative individuals. However, uptake of PrEP has been suboptimal in sub-Saharan Africa. The goal of this qualitative study was to identify facilitators of and barriers to PrEP acceptability among target users not taking PrEP. Fifty-nine individuals belonging to Ugandan priority populations participated in a single in-depth interview. Participants perceived themselves as being at high risk for HIV acquisition, and expressed interest in PrEP as an HIV prevention strategy. Two forms of stigma emerged as potential barriers to PrEP use: (1) misidentification as living with HIV; and (2) disclosure of membership in a priority population. Acceptability of PrEP was dampened for this sample of potential PrEP users due to anticipated stigmatization. Mitigating stigma should be a key component of effective PrEP delivery to reach UNAIDS goal of ending the AIDS epidemic by 2030.

Patients' and Providers' Views on Optimal Evidence-Based and Scalable Interventions for Individuals at High Risk of HIV Treatment Failure: Sequential Explorations Among Key Stakeholders in Cape Town, South Africa.

To support translation of evidence-based interventions into practice for HIV patients at high risk of treatment failure, we conducted qualitative research in Cape Town, South Africa. After local health officials vetted interventions as potentially scalable, we held 41 in-depth interviews with patients with elevated viral load or a 3-month treatment gap at community clinics, followed by focus group discussions (FGDs) with 20 providers (physicians/nurses, counselors, and community health care workers). Interviews queried treatment barriers, solutions, and specific intervention options, including motivational text messages, data-informed counseling, individual counseling, peer support groups, check-in texts, and treatment buddies. Based on patients' preferences, motivational texts and treatment buddies were removed from consideration in subsequent FGDs. Patients most preferred peer support groups and check-in texts while individual counseling garnered the broadest support among providers. Check-in texts, peer support groups, and data-informed counseling were also endorsed by provider sub-groups. These strategies warrant attention for scale-up in South Africa and other resource-constrained settings.

Perceptions About Local ART Adherence Norms and Personal Adherence Behavior Among Adults Living with HIV in Rural Uganda.

Although misperceived norms often drive personal health behaviors, we do not know about this phenomenon in the context of antiretroviral therapy (ART) adherence. We conducted a cross-sectional study including all persons living with HIV (PLWH) on ART across eight villages in one parish in a rural region of southwestern Uganda. We used surveys to measure personal reports of ART adherence (not missing any doses of ART in the past 7 days was considered optimal adherence whereas missing doses was considered suboptimal adherence) and perceived norms about the local ART adherence norm (whether or not each individual thought 'most other PLWH on ART in this parish' missed any doses in the past 7 days). Multivariable Poisson regression models were used to estimate the association between perceived norms and personal adherence. Among 159 PLWH on ART (95% response rate), 142 (89%) reported no missed doses. However, 119 (75%) thought most individuals in this population of PLWH on ART were sub-optimally adherent. This misperception about the local ART adherence norm was prevalent in every subgroup of PLWH. Misperceiving the local ART adherence norm to be sub-optimal adherence was associated with a reduced likelihood of optimal adherence among married PLWH (adjusted relative risk [aRR] = 0.83; 95% confidence interval [CI] 0.71-0.97). The association was similar but imprecisely estimated for all PLWH (aRR = 0.91; 95% CI 0.82-1.01). Interventions to correct misperceived ART adherence norms as a stand-alone intervention or as a complement to other adherence promotion programs may influence ART adherence behavior and perhaps reduce HIV-related stigma.

RESUMEN: Aunque las normas mal percibidas impulsan los comportamientos personales de salud, no sabemos acerca de este fenómeno en el contexto de la terapia antirretroviral (TAR). Este estudio transversal incluyó a todas las personas que viven con el VIH (PVVS) y con TAR en ocho pueblos de una parroquia en una región rural del suroeste de Uganda. Utilizamos encuestas para medir los informes de adherencia personal al TAR (no faltar ninguna dosis de TAR en los últimos 7 días se consideró como acción óptima; mientras que faltar las dosis se consideraron como acción subóptima) y las normas percibidas sobre la norma local de adherencia al TAR (si cada individuo pensó o no que 'la mayoría de las otras PVVS en esta parroquia omitieron alguna dosis en los últimos 7 días). Usamos modelos multivariables de regresión de Poisson para estimar la asociación entre las normas percibidas y la adherencia personal. De las 159 PVVS con TAR (tasa de respuesta del 95%), 142 (89%) reportaron que no faltaron ningua dosis. Sin embargo, 119 (75%) pensaron que la mayoría de los individuos en esta población de PVVS con TAR eran suboptimalmente adherentes. Esta percepción incorrecta sobre la norma local de adherencia al TAR fue prevalente en todos los subgrupos de PVVS. La percepción incorrecta de que la norma local de adherencia al TAR era subóptima se asoció con una menor probabilidad de adherencia óptima entre las PVVS casadas (riesgo relativo ajustado [aRR] = 0,83; intervalo de confianza [IC] del 95% 0,71-0,97). La asociación fue similar pero imprecisamente se estima para todas las PVVS (aRR = 0,91; IC 95% 0,82-1,01). Las intervenciones para corregir las normas mal percibidas de TAR, como una intervención independiente o como un complemento de otros programas de promoción de la adherencia, pueden influir en el comportamiento de la adherencia al TAR y tal vez reducir el estigma relacionado con el VIH.