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The Samoan Islands constitute a volcanic archipelago covering 1,170 square miles of the central South Pacific Ocean in the mid-Westem part of the Polynesian triangle. The Islands are divided into [...]

: Introduction: Antiretroviral therapy (ART) and tuberculosis preventive treatment (TPT) both prevent tuberculosis (TB) disease and deaths among people living with HIV. Differentiated care models, including community‐based care, can increase the uptake of ART and TPT to prevent TB in settings with a high burden of HIV‐associated TB, particularly among men. Methods: We developed a gender‐stratified dynamic model of TB and HIV transmission and disease progression among 100,000 adults ages 15−59 in KwaZulu‐Natal, South Africa. We drew model parameters from a community‐based ART initiation and resupply trial in sub‐Saharan Africa (Delivery Optimization for Antiretroviral Therapy, DO ART) and other scientific literature. We simulated the impacts of community‐based ART and TPT care programmes during 2018−2027, assuming that community‐based ART and TPT care were scaled up to similar levels as in the DO ART trial (i.e. ART coverage increasing from 49% to 82% among men and from 69% to 83% among women) and sustained for 10 years. We projected the number of TB cases, deaths and disability‐adjusted life years (DALYs) averted relative to standard, clinic‐based care. We calculated programme costs and incremental cost‐effectiveness ratios from the provider perspective. Results: If community‐based ART care could be implemented with similar effectiveness to the DO ART trial, increased ART coverage could reduce TB incidence by 27.0% (range 21.3%−34.1%) and TB mortality by 34.6% (range 24.8%–42.2%) after 10 years. Increasing both ART and TPT uptake through community‐based ART with TPT care could reduce TB incidence by 29.7% (range 23.9%−36.0%) and TB mortality by 36.0% (range 26.9%−43.8%). Community‐based ART with TPT care reduced gender disparities in TB mortality rates, with a projected 54 more deaths annually among men than women (range 11–103) after 10 years of community‐based care versus 109 (range 41–182) in standard care. Over 10 years, the mean cost per DALY averted by community‐based ART with TPT care was $846 USD (range $709–$1012). Conclusions: By substantially increasing coverage of ART and TPT, community‐based care for people living with HIV could reduce TB incidence and mortality in settings with high burdens of HIV‐associated TB and reduce TB gender disparities., INTRODUCTION Tuberculosis (TB) is the leading cause of death globally among people living with HIV (PLWH) [1]. HIV acquisition markedly increases the risk of progression to active TB disease [2]. [...]

Background Expanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies. Methods and findings In a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion ([greater than or equal to]11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher's exact test (two-sided [alpha] = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p < 0.001), SAT (0.92; 97.5% CI [0.89, 0.94] p < 0.001), and Choice (0.93; 97.5% CI [0.91, 0.96] p < 0.001) arms. There was no difference in acceptance and completion between any 2 arms overall or in prespecified subgroup analyses based on sex, age, time on antiretroviral therapy, and history of prior treatment for TB or TB infection. Only 14 (0.8%) participants experienced an adverse event prompting discontinuation of 3HP. The main limitation of the study is that it was conducted in a single center. Multicenter studies are now needed to confirm the feasibility and generalizability of the facilitated 3HP delivery strategies in other settings. Conclusions Short-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers. Trial Registration ClinicalTrials.gov NCT03934931., Author(s): Fred C. Semitala 1,2,3, Jillian L. Kadota 4,5, Allan Musinguzi 2, Fred Welishe 2, Anne Nakitende 2, Lydia Akello 2, Lynn Kunihira Tinka 2, Jane Nakimuli 2, Joan Ritar [...]

Background Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial randomised 14 communities to receive the 'PopART' intervention during 2014 to 2017 (7 arm A and 7 arm B communities) and 7 communities to receive standard-of-care (arm C). The intervention was delivered door-to-door by community HIV care providers (CHiPs) and included universal HIV testing, facilitated linkage to HIV care at government health clinics, and systematic TB symptom screening. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study aimed to measure the impact of delivering the PopART intervention on TB outcomes, in communities with high HIV and TB prevalence. Methods and findings The study population of the HPTN 071 (PopART) trial included individuals aged [greater than or equal to]15 years living in 21 urban and peri-urban communities in Zambia and South Africa, with a total population of approximately 1 million and an adult HIV prevalence of around 15% at the time of the trial. Two sputum samples for TB testing were provided to CHiPs by individuals who reported [greater than or equal to]1 TB suggestive symptom (a cough for [greater than or equal to]2 weeks, unintentional weight loss [greater than or equal to]1.5 kg in the last month, or current night sweats) or that a household member was currently on TB treatment. Antiretroviral therapy (ART) was offered universally at clinics in arm A and according to local guidelines in arms B and C. The TREATS study was conducted in the same 21 communities as the HPTN 071 (PopART) trial between 2017 and 2022, and TB prevalence was a co-primary endpoint of the TREATS study. The primary comparison was between the PopART intervention (arms A and B combined) and the standard-of-care (arm C). During 2019 to 2021, a TB prevalence survey was conducted among randomly selected individuals aged [greater than or equal to]15 years (approximately 1,750 per community in arms A and B, approximately 3,500 in arm C). Participants were screened on TB symptoms and chest X-ray, with diagnostic testing using Xpert-Ultra followed by culture for individuals who screened positive. Sputum eligibility was determined by the presence of a cough for [greater than or equal to]2 weeks, or [greater than or equal to]2 of 5 'TB suggestive' symptoms (cough, weight loss for [greater than or equal to]4 weeks, night sweats, chest pain, and fever for [greater than or equal to]2 weeks), or chest X-ray CAD4TBv5 score [greater than or equal to]50, or no available X-ray results. TB prevalence was compared between trial arms using standard methods for cluster-randomised trials, with adjustment for age, sex, and HIV status, and multiple imputation was used for missing data on prevalent TB. Among 83,092 individuals who were eligible for the survey, 49,556 (59.6%) participated, 8,083 (16.3%) screened positive, 90.8% (7,336/8,083) provided 2 sputum samples for Xpert-Ultra testing, and 308 (4.2%) required culture confirmation. Overall, estimated TB prevalence was 0.92% (457/49,556). The geometric means of 7 community-level prevalence estimates were 0.91%, 0.70%, and 0.69% in arms A, B, and C, respectively, with no evidence of a difference comparing arms A and B combined with arm C (adjusted prevalence ratio 1.14, 95% confidence interval, CI [0.67, 1.95], p = 0.60). TB prevalence was higher among people living with HIV than HIV-negative individuals, with an age-sex-community adjusted odds ratio of 2.29 [95% CI 1.54, 3.41] in Zambian communities and 1.61 [95% CI 1.13, 2.30] in South African communities. The primary limitations are that the study was powered to detect only large reductions in TB prevalence in the intervention arm compared with standard-of-care, and the between-community variation in TB prevalence was larger than anticipated. Conclusions There was no evidence that the PopART intervention reduced TB prevalence. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of several years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB. Trial registration The TREATS study was registered with ClinicalTrials.gov Identifier: NCT03739736 on November 14, 2018. The HPTN 071 (PopART) trial was registered at ClinicalTrials.gov under number NCT01900977 on July 17, 2013., Author(s): Eveline Klinkenberg 1,2,3,*, Sian Floyd 1,*, Kwame Shanaube 4, Linda Mureithi 5, Thomas Gachie 1,4, Petra de Haas 3, Barry Kosloff 1,4, Peter J. Dodd 6, Maria Ruperez 1, [...]

Background Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention. Methods and findings We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded. Conclusions In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context. Trial registration This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698)., Author(s): Nyashadzaishe Mafirakureva 1, Sushant Mukherjee 2, Mikhael de Souza 2, Cassandra Kelly-Cirino 2, Mario J. P. Songane 2, Jennifer Cohn 3, Jean-François Lemaire 2, Martina Casenghi 2, Peter J. [...]

: Introduction: Tuberculosis (TB) causes one‐third of HIV‐related deaths worldwide, making TB preventive treatment (TPT) a critical element of HIV programmes. Approximately 16% of people living with HIV (PLHIV) on antiretrovirals in Zimbabwe are enrolled in the Fast Track (FT) differentiated service delivery model, which includes multi‐month dispensing of antiretrovirals and quarterly health facility (HF) visits. We assessed the feasibility and acceptability of utilizing FT to deliver 3HP (3 months of once‐weekly rifapentine and isoniazid) for TPT by aligning TPT and HIV visits, providing multi‐month dispensing of 3HP, and using phone‐based monitoring and adherence support. Methods: We recruited a purposive sample of 50 PLHIV enrolled in FT at a high‐volume HF in urban Zimbabwe. At enrolment, participants provided written informed consent, completed a baseline survey, and received counselling, education and a 3‐month supply of 3HP. A study nurse mentor called participants at weeks 2, 4 and 8 to monitor and support adherence and side effects. When participants returned for their routine 3‐month FT visit, they completed another survey, and study staff conducted a structured medical record review. In‐depth interviews were conducted with providers who participated in the pilot. Results: Participants were enrolled between April and June 2021 and followed through September 2021. Median age = 32 years (IQR 24,41), 50% female, median time in FT 1.8 years (IQR 0.8,2.7). Forty‐eight participants (96%) completed 3HP in 13 weeks; one completed in 16 weeks, and one stopped due to jaundice. Most participants (94%) reported “always” or “almost always” taking 3HP correctly. All reported they were very satisfied with the counselling, education, support and quality of care they received from providers and FT service efficiency. Almost all (98%) said they would recommend it to other PLHIV. Challenges reported included pill burden (12%) and tolerability (24%), but none had difficulty with phone‐based counselling or wished for additional HF‐based visits. Discussion: Using FT to deliver 3HP was feasible and acceptable. Some reported tolerability challenges but 98% completed 3HP, and all appreciated the efficiency of aligning TPT and HIV HF visits, multi‐month dispensing and phone‐based counselling. Conclusions: Scaling up this approach could expand TPT coverage in Zimbabwe., INTRODUCTION Tuberculosis (TB) is the second leading cause of death from an infectious disease, causing 1.6 million deaths in 2021 [1]. Despite the scale‐up of antiretroviral therapy (ART), people living [...]

The risk of tuberculosis (TB) disease is increased in children with chronic kidney disease (CKD), even higher in stage 5 CKD/kidney failure and especially high after kidney transplantation due to immunosuppression. TB disease may follow recent primary infection, or result from reactivation of latent infection. Reactivation is more common in adults, while progression following primary infection makes up a greater proportion of disease in children. Recommendations for preventing TB disease in some low TB incidence countries have previously included offering Bacillus Calmette-Guérin (BCG) vaccine to all children listed for kidney transplant if they had not received this as part of previous national immunisation programmes. Based on the available evidence, we recommend modifying this practice, focusing instead on awareness of risk factors for TB exposure, infection and disease and the use of appropriate testing strategies to identify and treat TB infection and disease., Author(s): Alasdair Bamford [sup.1] [sup.2] , Garth Dixon [sup.3] [sup.2] , Nigel Klein [sup.1] [sup.2] , Stephen D. Marks [sup.4] [sup.2] , Nicole Ritz [sup.5] [sup.6] , Steven B. Welch [...]