Adherence
Background: Treatment of latent tuberculosis infection (LTBI) is effective in preventing progression to TB disease. This study aimed to synthesize available evidence on the efficacy, adherence, and safety of LTBI treatment in order to assist policymakers to design appropriate national treatment policies and treatment protocols.
Method: The PRISMA statement extension for systematic reviews incorporating network meta-analysis (PRISMA-NMA) was used to review and report this research. Randomized controlled trials which compared the efficacy and safety of LTBI treatments were included. A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL). The network meta-analysis was done using R- studio Version 1.4.1103.
Result: In this review, 42 studies were included, which enrolled 52547 participants living with HIV, chronic Silicosis, had contact history with TB infected person, immigrants, prisoners, old people, and pregnant women who were at risk for latent TB were included. The incidence of TB among people living with HIV who have taken 3RHZ (RR 0.40 95% CI 0.23,0.69) as TPT was lower followed by 3RH (RR 0.56 95% CI 0.36,0.89) and 6H (RR 0.62 95% CI 0.45, 0.87). However, 3HP (RR 0.38 95% CI 0.15,0.99) shows a significant reduction on the incidence of TB among HIV negative patients who had TB contact history. Patients’ adherence to TPT was higher among patients who have taken 4R (RR1.38 95% CI 1.0,1.89) followed by 3RH (RR 1.34 95% CI 1.03,1.74) and 2RZ (RR 1.34 95% CI 1.02,1.75).
The proportion of subjects who permanently discontinued a study drug because of adverse event were higher in 3RZ (RR 9.31 95% CI 2.99,28.97), followed by 2RZ (RR7.12 95% CI 1.39, 36.57), and 3RH (RR 3.29 95% CI 1.11, 9.78). The risk of nausea and vomiting was higher among patients who have taken 3HP (RR 5.91 95% CI 2.30,15.20), followed by two months twice a week combination of HP (RR 3.51 95% CI 1.04,11.79). Furthermore, the risk of grade 3 and 4 liver toxicity was significantly higher among patients who have taken 12H (RR 26.04 95%CI 5.88,115.38), followed by 2RZ (RR 18.48 95% CI 4.57,74.77).
Conclusion: From this review, it can be concluded that 3RHZ, 3RH, 6H has a significant impact on the reduction of TB incidence among PLWH and 3HP among HIV negative people who had TB contact history. However, rifampicin combination either with isoniazide or pyrazinamide or both were significantly associated with adverse events which resulted permanent discontinuation. This may support the current recommended TPT regimen of 3HP and 6H. Hence, inorder to understand the efficacy and safety of TPT on children more study might needs to be done.
Key words: Systematic review, Network meta-analysis, and Tuberculosis preventive therapy.