Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.

<h4>Background</h4>Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-ana...

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Autores principales:	Mercedes Yanes-Lane, Edgar Ortiz-Brizuela, Jonathon R Campbell, Andrea Benedetti, Gavin Churchyard, Olivia Oxlade, Dick Menzies
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/3c3fb56e2eb942d590ce869d167b5ac9
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spelling	oai:doaj.org-article:3c3fb56e2eb942d590ce869d167b5ac92021-12-02T19:56:06ZTuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.1549-12771549-167610.1371/journal.pmed.1003738https://doaj.org/article/3c3fb56e2eb942d590ce869d167b5ac92021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.1003738https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials.<h4>Methods and findings</h4>We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children.<h4>Conclusions</h4>Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.Mercedes Yanes-LaneEdgar Ortiz-BrizuelaJonathon R CampbellAndrea BenedettiGavin ChurchyardOlivia OxladeDick MenziesPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 18, Iss 9, p e1003738 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Mercedes Yanes-Lane Edgar Ortiz-Brizuela Jonathon R Campbell Andrea Benedetti Gavin Churchyard Olivia Oxlade Dick Menzies Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.
description	<h4>Background</h4>Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials.<h4>Methods and findings</h4>We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children.<h4>Conclusions</h4>Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.
format	article
author	Mercedes Yanes-Lane Edgar Ortiz-Brizuela Jonathon R Campbell Andrea Benedetti Gavin Churchyard Olivia Oxlade Dick Menzies
author_facet	Mercedes Yanes-Lane Edgar Ortiz-Brizuela Jonathon R Campbell Andrea Benedetti Gavin Churchyard Olivia Oxlade Dick Menzies
author_sort	Mercedes Yanes-Lane
title	Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.
title_short	Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.
title_full	Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.
title_fullStr	Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.
title_full_unstemmed	Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.
title_sort	tuberculosis preventive therapy for people living with hiv: a systematic review and network meta-analysis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3c3fb56e2eb942d590ce869d167b5ac9
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Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.

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