PMID- 34520459 OWN - NLM STAT- MEDLINE DCOM- 20211130 LR - 20220929 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 18 IP - 9 DP - 2021 Sep TI - Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis. PG - e1003738 LID - 10.1371/journal.pmed.1003738 [doi] LID - e1003738 AB - BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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. FAU - Yanes-Lane, Mercedes AU - Yanes-Lane M AD - Respiratory Epidemiology and Clinical Research Unit, McGill International TB Centre, McGill University, Montreal, Quebec, Canada. FAU - Ortiz-Brizuela, Edgar AU - Ortiz-Brizuela E AUID- ORCID: 0000-0001-7169-8459 AD - Respiratory Epidemiology and Clinical Research Unit, McGill International TB Centre, McGill University, Montreal, Quebec, Canada. AD - Department of Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. FAU - Campbell, Jonathon R AU - Campbell JR AUID- ORCID: 0000-0003-2341-2166 AD - Respiratory Epidemiology and Clinical Research Unit, McGill International TB Centre, McGill University, Montreal, Quebec, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. FAU - Benedetti, Andrea AU - Benedetti A AD - Respiratory Epidemiology and Clinical Research Unit, McGill International TB Centre, McGill University, Montreal, Quebec, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. AD - Department of Medicine, McGill University, Montreal, Canada. FAU - Churchyard, Gavin AU - Churchyard G AUID- ORCID: 0000-0002-4269-3699 AD - The Aurum Institute, Parktown, South Africa. AD - School of Public Health, University of Witwatersrand, Johannesburg, South Africa. FAU - Oxlade, Olivia AU - Oxlade O AUID- ORCID: 0000-0002-4834-8327 AD - Respiratory Epidemiology and Clinical Research Unit, McGill International TB Centre, McGill University, Montreal, Quebec, Canada. FAU - Menzies, Dick AU - Menzies D AUID- ORCID: 0000-0003-1601-4514 AD - Respiratory Epidemiology and Clinical Research Unit, McGill International TB Centre, McGill University, Montreal, Quebec, Canada. AD - Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada. LA - eng GR - UM1 AI154463/AI/NIAID NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20210914 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 0 (Anti-Retroviral Agents) RN - 0 (Antitubercular Agents) RN - 0 (Rifamycins) RN - V83O1VOZ8L (Isoniazid) SB - IM CIN - Tuberculosis preventive treatment in people living with HIV - is the glass half empty, or half full? CIN - Economic and modelling evidence for tuberculosis preventive therapy among people living with HIV: a systematic review & meta-analysis. CIN - The Latent Tuberculosis Cascade-of-Care Among People Living with HIV: A Systematic Review and Meta-Analysis. MH - Adolescent MH - Adult MH - Aged MH - Anti-Retroviral Agents/adverse effects/*therapeutic use MH - Antitubercular Agents/adverse effects/*therapeutic use MH - Child MH - Child, Preschool MH - *Coinfection MH - Female MH - HIV Infections/diagnosis/*drug therapy/epidemiology/virology MH - *HIV Long-Term Survivors MH - Humans MH - Infant MH - Isoniazid/therapeutic use MH - Male MH - Middle Aged MH - *Preventive Health Services MH - Rifamycins/therapeutic use MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome MH - Tuberculosis/diagnosis/epidemiology/microbiology/*prevention & control MH - Young Adult PMC - PMC8439495 COIS- The authors have declared that no competing interests exist. EDAT- 2021/09/15 06:00 MHDA- 2021/12/01 06:00 PMCR- 2021/09/14 CRDT- 2021/09/14 17:25 PHST- 2020/12/11 00:00 [received] PHST- 2021/07/18 00:00 [accepted] PHST- 2021/09/14 17:25 [entrez] PHST- 2021/09/15 06:00 [pubmed] PHST- 2021/12/01 06:00 [medline] PHST- 2021/09/14 00:00 [pmc-release] AID - PMEDICINE-D-20-06010 [pii] AID - 10.1371/journal.pmed.1003738 [doi] PST - epublish SO - PLoS Med. 2021 Sep 14;18(9):e1003738. doi: 10.1371/journal.pmed.1003738. eCollection 2021 Sep.