The latent tuberculosis cascade-of-care among people living with HIV: A systematic review and meta-analysis
Authors: Bastos Mayara Lisboa , Melnychuk Luca , Campbell Jonathon R. , Oxlade Olivia , Menzies Dick 
Published: September 2021

Background
Tuberculosis preventive therapy (TPT) reduces TB-related morbidity and mortality in people living with HIV (PLHIV). Cascade-of-care analyses help identify gaps and barriers in care and develop targeted solutions. A previous latent tuberculosis infection (LTBI) cascade-of-care analysis showed only 18% of persons in at-risk populations complete TPT, but a similar analysis for TPT among PLHIV has not been completed. We conducted a meta-analysis to provide this evidence.

Methods and findings
We first screened potential articles from a LTBI cascade-of-care systematic review published in 2016. From this study, we included cohorts that reported a minimum of 25 PLHIV. To identify new cohorts, we used a similar search strategy restricted to PLHIV. The search was conducted in Medline, Embase, Health Star, and LILACS, from January 2014 to February 2021. Two authors independently screened titles and full text and assessed risk of bias using the Newcastle–Ottawa Scale for cohorts and Cochrane Risk of Bias for cluster randomized trials. We meta-analyzed the proportion of PLHIV completing each step of the LTBI cascade-of-care and estimated the cumulative proportion retained. These results were stratified based on cascades-of-care that used or did not use LTBI testing to determine eligibility for TPT. We also performed a narrative synthesis of enablers and barriers of the cascade-of-care identified at different steps of the cascade.
A total of 71 cohorts were included, and 70 were meta-analyzed, comprising 94,011 PLHIV. Among the PLHIV included, 35.3% (33,139/94,011) were from the Americas and 29.2% (27,460/94,011) from Africa. Overall, 49.9% (46,903/94,011) from low- and middle-income countries, median age was 38.0 [interquartile range (IQR) 34.0;43.6], and 65.9% (46,328/70,297) were men, 43.6% (29,629/67,947) were treated with antiretroviral therapy (ART), and the median CD4 count was 390 cell/mm3 (IQR 312;458). Among the cohorts that did not use LTBI tests, the cumulative proportion of PLHIV starting and completing TPT were 40.9% (95% CI: 39.3% to 42.7%) and 33.2% (95% CI: 31.6% to 34.9%). Among cohorts that used LTBI tests, the cumulative proportions of PLHIV starting and completing TPT were 60.4% (95% CI: 58.1% to 62.6%) and 41.9% (95% CI:39.6% to 44.2%), respectively. Completion of TPT was not significantly different in high- compared to low- and middle-income countries. Regardless of LTBI test use, substantial losses in the cascade-of-care occurred before treatment initiation. The integration of HIV and TB care was considered an enabler of the cascade-of-care in multiple cohorts. Key limitations of this systematic review are the observational nature of the included studies, potential selection bias in the population selection, only 14 cohorts reported all steps of the cascade-of-care, and barriers/facilitators were not systematically reported in all cohorts.

Conclusions
Although substantial losses were seen in multiple stages of the cascade-of-care, the cumulative proportion of PLHIV completing TPT was higher than previously reported among other at-risk populations. The use of LTBI testing in PLHIV in low- and middle-income countries was associated with higher proportion of the cohorts initiating TPT and with similar rates of completion of TPT.