Lucy Chimoyi

Background: Tuberculosis-preventive treatment (TPT) is recommended for those at risk of tuberculosis, but despite encouraging trial data, evidence of its effectiveness from routine settings with diverse TPT regimens is limited. We describe routine TPT implementation outcomes in people living with human immunodeficiency virus (HIV; PLWH) to identify bottlenecks and opportunities for improvement along the cascade of care. Methods: From 2021–2023, we conducted a 24-month prospective cohort study of PLWH facilities in Ethiopia, South Africa and Zimbabwe. Sociodemographic and clinical data were collected at enrollment. During follow-up, we collected TPT initiation, TPT-related adverse effects, and completion data. A subgroup was allocated digital boxes as a proxy measure for assessing treatment completion. Tuberculosis diagnoses were confirmed from clinic records or symptom agnostic sputum testing using Xpert MTB/RIF assay and mycobacteria growth indicator tube (MGIT) culture at 12- and 24 months after enrollment. Results: We enrolled 2095 participants, mostly female (n = 1489 [71.1%]), with a median age of 42 years (interquartile range, 35–50 years). Approximately 60% (n = 1312) were considered eligible for TPT, and 1110 (84.6%) initiated TPT within 60 days of antiretroviral therapy initiation or refill during follow-up (rifapentine and isoniazid [3HP] in 625 and 6 or 12 months of isoniazid [6H/12H] in 487). TPT was completed in 55.4% (406 of 733). Mild symptoms compatible with TPT adverse effects were commonly reported in 3HP versus 6H/12H (190 [31.0%] vs 51 [11.0%], respectively; P < .001]. The tuberculosis incidence rate was 1.27/100 person-years (95% confidence interval, .95–1.69) during study follow-up in a mostly long-term antiretroviral therapy population and was lower for PLWH who completed TPT (adjusted incidence rate ratio, 0.39 [.20–.78]; P = .01). Conclusions: There were losses along the cascade, particularly at completion. In programmatic settings, we observed more potential mild symptoms from 3HP compared to 6H/12H use. Interventions to support TPT completion are needed.

Background: TB preventive treatment (TPT) is recommended for those at risk of TB, but despite encouraging trial data, evidence of its effectiveness from routine settings with diverse TPT regimens is limited. We describe routine TPT implementation outcomes in people living with HIV (PLWH) to identify bottlenecks and opportunities for improvement along the cascade of care. Methods: From 2021-2023, we conducted a 24-month prospective cohort study of PLWH in nine health facilities in Ethiopia, South Africa and Zimbabwe. Socio-demographic and clinical data were collected at enrolment. During follow-up, we collected information on TPT initiation, TPT-related side effects and completion. A sub-group of PLWH were allocated digital boxes (evriMED1000) as a proxy measure for assessing treatment completion. TB case ascertainment was based on confirmed diagnoses abstracted from clinic records and symptom agnostic sputum testing initially using Xpert MTB/RIF assay and subsequently MGIT culture at 12- and 24-months post-enrolment. Results: We enrolled 2,095 participants, mostly female (n=1,489; 71.1%), of median age 42 years [interquartile range: 35-50]. Approximately 60% were considered eligible for TPT (n=1,312) and 1,110 (84.6%) were initiated on TPT within 60 days of ART initiation or at a refill visit during the observation period (n=625 on 3HP and n=487 on 6H/12H). TPT completion via digital pillbox assessment was 55.4% (n=406/733). Symptoms compatible with TPT side effects were commonly reported in 3HP vs.6H/12H [190(31.0%) vs. 51(11.0%)]. TB incidence rate was 1.27 (95%CI: 0.95-1.69)/100 person-years during study follow-up in a mostly long-term ART population and was lower for PLWH who completed TPT (aIRR: 0.39; 95% CI: 0.20-0.78, p-value: 0.01). Conclusions: There were losses along the cascade, particularly at completion. In programmatic settings, we observed more potential side effects in 3HP compared to 6H/12H. Interventions to support TPT completion are needed. Author Summary: What is already known on this topic: Clinical trials have shown that 3HP is well tolerated and has higher completion rates than 6H/12H. Identifying bottlenecks to and determinants of successful TPT implementation in programmatic settings is necessary. What this study adds: In a multi-site and country cohort of 2,095 PLWH attending routine HIV care, we observed that most individuals could be initiated on TPT and that side effects were generally mild but correlated with not completing TPT There are gaps in adhering to guidelines especially on the prescription of TPT to PLWH with prior TB. Clinical reporting (defined as date of TPT completion from clinic records) of TPT completion is an overestimation: only slightly more than half of participants initiated on TPT completed it as assessed by the digital pillbox (Medication Event Reminder Monitor-MERM). Incident TB disease (often asymptomatic) occurred among 2.5% of participants over the two years of follow-up. TPT, even at the relatively low rates of completion reported by the digital pillbox, appeared to reduce the rate of incident TB disease by 61%. How this study might affect research, practice or policy: These findings should reassure clinical providers that most patients can be safely initiated on any TPT regimen, that side effects are generally self-limiting and do not require clinical intervention, and that TPT is effective in protecting against incident TB disease. These results emphasize the need for additional approaches to support TPT prescribing and patient-level adherence and regimen completion. Tools to accurately measure TPT completion are required. These findings show that providers should be encouraged to initiate TPT to all eligible PLWH to close the existing gaps. While improved adherence might lead to a reduced TB incidence rate, the impact with the current programmatic implementation still has public health importance. This is an important point as countries navigate a resource-constrained future.

Background: Tuberculosis (TB) preventive treatment (TPT) is crucial in reducing the TB burden among people living with HIV (PLHIV), particularly in high TB/HIV burden countries like Ethiopia, South Africa, and Zimbabwe. Despite the availability of shorter TPT regimens, suboptimal treatment completion persists, and subnational variations remain poorly understood. Methods: This study utilized geospatial analyses of treatment completion data from the Opt4TPT study, a prospective cohort conducted in Ethiopia, South Africa, and Zimbabwe (2021–2023). Participants’ demographic and clinical data were included, and geospatial patterns were assessed using QGIS and local indicators of spatial autocorrelation (LISA) to identify clusters of treatment outcomes. Results: Of the 1,320 participants enrolled, 1,076 (81.5%) had geolocated data, and 90.1% reported completing TPT. Treatment non-completion clustered near clinics in all three countries. LISA analysis identified spatial cold spots for low treatment completion near clinics in South Africa and Zimbabwe, but not in Ethiopia. Distribution of demographic and clinical factors did not align with treatment outcomes. Conclusions: Geospatial analyses revealed clustering of non-completion near clinics, warranting further research on contextual factors, including stigma and facility-switching behavior. These findings emphasize the potential of geospatial tools in optimizing TPT programs through locally tailored interventions.

Vaccines used in National Immunization Programmes (NIPs) are known to be safe and effective if used correctly, however, no vaccine is completely risk-free as adverse events occasionally occur after immunization. The World Health Organization (WHO) recommends adverse event following immunization (AEFI) surveillance for all vaccines as a critical tool to monitor safety and address potential concerns. However, the factors contributing to Uganda's inability to meet global vaccine safety indicators remain unclear. This study assessed the level of knowledge and reporting of AEFI of children among healthcare workers and caregivers at Mengo Hospital, Kampala. A cross-sectional mixed-methods study involving three focus group discussions, each consisting of five caregivers, eight key informant interviews with healthcare workers (HCWs) and 388 face-to-face interviews with caregivers was carried out. Caregivers accompanying their children for their routine vaccination visits were invited to participate in the study. We descriptively summarized data using measures of central tendency, dispersion, and frequencies. Crude and adjusted measures of association between predictors and AEFI reporting were assessed using Pearson's Chi-square test, and binary logistic regression analysis respectively. Thematic analysis was used to identify behavioral, personal, and social patterns influencing knowledge and reporting of adverse events following immunization among caregivers and HCWs. Approximately one-third of caregivers (130, 33.5%) reported that their children experienced an AEFI and reported it to a healthcare facility. Significant predictors of AEFI reporting included having a secondary education (aOR = 3.56, 95% CI: 1.12-11.30), tertiary education or higher (aOR = 8.52, 95% CI: 2.09-34.81), being older than 35 years (aOR= 18.77; 95% CI: 2.34-150.60) and unmarried (aOR = 3.27, 95% CI: 1.51-7.12). While most HCWs had good AEFI knowledge, they lacked awareness of the national reporting system. Strengthening training for HCWs and raising awareness among caregivers is essential to improve AEFI surveillance.

Background: Because of the association of mental health and substance use disorders with higher HIV mortality and decreased retention in care, we investigated their frequency and impact on tuberculosis preventive therapy (TPT) adherence and completion among people with HIV (PWHIV) initiating TPT. Methods: We conducted a prospective, longitudinal cohort study with a nested mixed methods study in 2 Johannesburg, South Africa, facilities. Participants were PWHIV on antiretroviral therapy initiating TPT between August and December 2023. We measured TPT adherence and completion with electronic medication boxes. We used validated tools to measure symptoms of anxiety, depression, alcohol use, and other substance use at enrollment and 12 weeks. We constructed multivariable regression models to determine associations of these variables with TPT adherence and completion, adjusting for age, sex, and time on antiretroviral therapy. We interviewed participants about mental health and experiences with TPT and analyzed responses using deductive content analysis. Results: Among 224 PWHIV, 111 (50%) completed TPT. Eighty-one (36%) screened positive for depression symptoms and 63 (28%) for anxiety symptoms. Seventy-six (34%) reported unhealthy alcohol use and 60 (27%) tobacco use. Using multivariable models adjusting for confounders, only depression symptoms were significantly and negatively associated with adherence (9% fewer doses; 95% confidence interval, .4–16; P = .032) and completion (odds ratio, 0.48; 95% confidence interval, .26–.90; P = .021). Participant narratives highlighted the negative influence of mental health on adherence and the need for social and psychological support services. Conclusions: Symptoms of depression, anxiety, unhealthy alcohol use, and tobacco use were common among PWHIV initiating TPT. Depression symptoms were strongly and independently associated with TPT nonadherence and noncompletion.

Introduction Differentiated service delivery (DSD) models, which are mechanisms of HIV care that reduce provider visits and offer varied ART delivery methods, are scaling up across sub- Saharan Africa. It is unknown how the movement of patients to DSD models impacts services beyond ART, including the uptake and completion of tuberculosis preventive therapy (TPT). Methods Using the RE-AIM framework, we analyzed data from Opt4TPT, a longitudinal cohort study examining TPT delivery in South Africa and Zimbabwe. We constructed multivariate logistic regression models to evaluate the association of receiving ART from a DSD model with the proportion of participants who initiated and completed TPT, as measured by electronic medication boxes. We constructed a Cox proportional hazards model to assess the association between DSD models and time to TPT initiation. Results Among 1193 participants, 276 received ART through a DSD model, while 917 used the conventional model. Overall, 1035 (87%) initiated TPT, including 242 (88%) in DSD models and 793 (86%) in conventional models. Receiving ART from a DSD model was not significantly associated (OR 1.11, 95% CI 0.74-1.67, p = 0.61) with TPT initiation. DSD models had a significantly longer mean time to initiation (6.5 vs. 2.7 days, p = 0.01). Of the 731 (71%) participants with MERM box data, 356 (49%) completed TPT. Bivariate analysis showed significantly higher odds of completing TPT among those in DSD models (OR 1.53, 95% CI 1.06- 2.21, p=0.024). This association was not significant in multivariate analysis after adjusting for demographic and clinical factors (OR 0.89, 95% CI 0.58-1.36, p=0.58). Conclusions We found high TPT uptake in DSD and conventional models of care, indicating that TPT delivery in DSD models is feasible. We found low TPT completion in both models of care, showing a need to focus on improving TPT completion overall.

Scaling up of newer innovations that address the limitations of the dried blood spot and the logistics of plasma monitoring is needed. We employed a multi-site, cross-sectional assessment of the plasma separation card (PSC) on blood specimens collected from all consenting adults, assenting young and pediatric patients living with HIV from 10 primary healthcare clinics in South Africa. Venous blood for EDTA-plasma samples was collected and analyzed according to the standard of care assay, while collected capillary blood for the PSC samples was analyzed using the Roche COBAS AmpliPrep/Cobas TaqMan (CAP/CTM) HIV-1 Test at the National Reference laboratories. McNemar tests assessed the differences in concordance between the centrifuged plasma and dried plasma spots. The usability of PSC by blood spotting, PSC preparation, and pre-analytical work was assessed by collecting seven-point Likert-scale data from healthcare and laboratory workers. We enrolled 538 patients, mostly adults [ n = 515, 95.7% (95% CI: 93.7%–97.1%)] and females [ n = 322, 64.2% (95% CI: 60.0%–68.1%)]. Overall, 536 paired samples were collected using both PSC- and EDTA-plasma diagnostics, and 502 paired PSC- and EDTA-plasma samples assessed. Concordance between the paired samples was obtained for 446 samples. Analysis of these 446 paired samples at 1,000 copies per milliliter threshold yielded an overall sensitivity of 87.5% [95% CI: 73.2%–95.8%] and specificity of 99.3% [95% CI: 97.9%–99.8%]. Laboratory staff reported technical difficulties in most tasks. The usability of the PSC by healthcare workers was favorable. For policymakers to consider PSC scale-up for viral load monitoring, technical challenges around using PSC at the clinic and laboratory level need to be addressed. IMPORTANCE: Findings from this manuscript emphasize the reliability of the plasma separation card (PSC), a novel diagnostic method that can be implemented in healthcare facilities in resource-constrained settings. The agreement of the PSC with the standard of care EDTA plasma for viral load monitoring is high. Since the findings showed that these tests were highly specific, we recommend a scale-up of PSC in South Africa for diagnosis of treatment failure.

Objective To explore the syndemic interaction between social, environmental, and structural contexts and HIV infection in peri-mining areas in South Africa. Design Mixed qualitative methods consisting of in-depth interviews (IDIs) and focus group discussions (FGDs) exploring the interaction between HIV infection and the social, environmental and structural factors affecting people living in the peri-mining areas of South Africa. Themes were analysed following the syndemic theoretical framework. Setting Participants were recruited from three mining companies and locations in the peri-mining communities surrounding the mining companies in Limpopo, Mpumalanga, and Northern Cape provinces. Participants Inclusion criteria included mineworkers, healthcare workers, female sex workers (FSWs), injection drug users (IDUs), and other community members, ≥18 years, living in the peri-mining area at the time of participation. Three FGDs were conducted (n=30): 13 men and 17 women aged 18–55 years. IDIs were conducted with 45 participants: mineworkers (n=10), healthcare workers (n=11), FSWs (n=15), truck drivers (n=4) and IDUs (n=5). Results The findings from this study indicate that a syndemic of four socio-behavioural factors is associated with HIV acquisition in peri-mining areas. These are migrancy, accessibility to alcohol and substance use, commercial and transactional sex, and uptake of HIV prevention services. Conclusions Our findings have implications for HIV prevention programmes in mining companies, which rely on male condom usage promotion. More emphasis on better education about HIV prevalence, transmission and up-to-date prevention alternatives, such as pre-exposure prophylaxis for mineworkers is recommended. Furthermore, collaboration with community-based organisations is recommended to wholly address the syndemic factors influencing HIV transmission in peri-mining communities.

Globally, high viral load (VL) suppression rates are indicators of successful HIV treatment programs. Evaluation of these programmes at lower levels is likely to highlight variations that are masked at the provincial or national levels. This ecological study used routinely collected clinical and surveillance data on the HIV programme from 88 sampled Ekurhuleni wards. Between January 2012 and December 2016, 26 222 HIV VL tests for 2817 patients were conducted. We conducted a secondary analysis to determine the predictors of high VL suppression accounting for space and time random effects and estimate the impact of the national universal test-and-treat roll-out in 2016 and forecast VL suppression rates for five years post-2016.The proportion of VL suppression increased over the years: 2012 (47.8%: 95% confidence interval (CI): 36.7%-67.4%); 2013 (58.2%: 95%CI: 41.4%-79.6%); 2014 (62.7%: 95%CI: 45.2%-84.7%); 2015 (67.2%: 95%CI: 49.0%-89.9%) and 2016 (61.2%: 95%CI: 43.9%-83.0%). For every percentage increase in ART initiation, high VL suppression rates increased by 35% (RR: 1.345; 95% credible interval (Crl) 1.221–1.492) and for every percentage increase in women in the ward, high VL suppression increased by 44% (RR: 1.442; 95%CrI: 1.056–1.962). There was evidence of high and low clusters of viral load suppression observed at ward-level. The VL suppression rates in Ekurhuleni were lower than the 90% UNAIDS target. There was heterogeneity of high VL suppression across wards and study period. Targeted interventions strengthening ART initiation and retention in care are critical to achieving optimal VL suppression in Ekurhuleni and districts with similar profiles.

People who live in the household of someone with infectious pulmonary tuberculosis are at a high risk of tuberculosis infection and subsequent progression to tuberculosis disease. These individuals are prioritized for contact investigation and tuberculosis preventive treatment (TPT). The treatment of TB infection is critical to prevent the progression of infection to disease and is prioritized in household contacts. Despite the availability of TPT, uptake in household contacts is poor. Multiple barriers prevent the optimal implementation of these policies. This manuscript lays out potential next steps for closing the policy-to-implementation gap in household contacts of all ages.