Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials.

Henok Tadesse Ayele,Thomas P A Debray,Maaike S M Van Mourik,Marc J M Bonten,Katalin Andrea Wilkinson

doi:10.1371/journal.pone.0142290

Henok Tadesse Ayele, Thomas P A Debray + Show 3 more

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https://doi.org/10.1371/journal.pone.0142290

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Journal: PloS one	Publication Date: Nov 9, 2015
Citations: 90	License type: CC BY 4.0

Affiliation: Dilla University, University Medical Center Utrecht

Abstract

BackgroundInfection with Human Immunodeficiency virus (HIV) is an important risk factor for Tuberculosis (TB). Anti-Retroviral Therapy (ART) has improved the prognosis of HIV and reduced the risk of TB infected patients. Isoniazid Preventive Therapy (IPT) aims to reduce the development of active TB in patients with latent TB.ObjectiveSystematically review and synthesize effect estimates of IPT for TB prevention in adult HIV patients. Secondary objectives were to assess the effect of IPT on HIV disease progression, all-cause mortality and adverse drug reaction (ADR).Search StrategyElectronic databases were searched to identify relevant articles in English available by September 11th 2015.Selection CriteriaResearch articles comparing IPT to placebo or no treatment in HIV infected adults using randomized clinical trials.Data AnalysisA qualitative review included study-level information on randomization and treatment allocation. Effect estimates were pooled using random-effects models to account for between-study heterogeneity.Main ResultsThis review assessed ten randomized clinical trials that assigned 7619 HIV patients to IPT or placebo. An overall 35% of TB risk reduction (RR = 0.65, 95% CI (0.51, 0.84)) was found in all participants, however, larger benefit of IPT was observed in Tuberculin Skin Test (TST) positive participants, with pooled relative risk reduction of 52% [RR = 0.48; 95% CI (0.29, 0.82)] and with a prediction interval ranging from 0.13 to 1.81. There was no statistically significant effect of IPT on TB occurrence in TST negative or unknown participants. IPT also reduced the risk of HIV disease progression in all participants (RR = 0.69; 95% CI (0.48, 0.99)) despite no benefits observed in TST strata. All-cause mortality was not affected by IPT although participants who had 12 months of IPT tend to have a reduced risk (RR = 0.65; 95% CI(0.47, 0.90)). IPT had an elevated, yet statistically non-significant, risk of adverse drug reaction [RR = 1.20; 95% CI (1.20, 1.71)]. Only a single study assessed the effect of IPT in combination with ART in preventing TB and occurrence of multi-drug resistant tuberculosis.ConclusionsIPT use substantially contributes in preventing TB in persons with HIV in general and in TST positive individuals in particular. More evidence is needed to explain discrepancies in the protective effect of IPT in these individuals.

Highlights

Mycobacterium tuberculosis (TB) is the most common cause of bacterial infection in humans [1,2,3] and is globally a leading cause of morbidity and mortality, especially in developing countries.[4]
An overall 35% of TB risk reduction (RR = 0.65, 95% CI (0.51, 0.84)) was found in all participants, larger benefit of Isoniazid Preventive Therapy (IPT) was observed in Tuberculin Skin Test (TST) positive participants, with pooled relative risk reduction of 52% [RR = 0.48; 95% CI (0.29, 0.82)] and with a prediction interval ranging from 0.13 to 1.81
IPT reduced the risk of Human Immunodeficiency virus (HIV) disease progression in all participants (RR = 0.69; 95% CI (0.48, 0.99)) despite no benefits observed in TST strata

Summary

Introduction

Mycobacterium tuberculosis (TB) is the most common cause of bacterial infection in humans [1,2,3] and is globally a leading cause of morbidity and mortality, especially in developing countries.[4]. Randomized controlled trials have demonstrated that a course of Isoniazid Preventive Therapy (IPT) reduces the incidence of TB disease in HIV-negative populations at risk of developing active disease.[15] In HIV infected patients, IPT reduced reactivation of latent TB infection, both in industrialized countries[16,17,18] as well as in developing countries.[19,20,21] observational studies in HIV-positive injecting drug users (IDU) suggested a potential benefit of IPT.[16], [17], [22,23,24]. The benefit appears to be higher in Tuberculin Skin Test (TST) positive patients than in TST negatives.[25] In addition, recent observational studies reported that the benefit of IPT increased if it is delivered in combination to ART.[26,27,28]. Isoniazid Preventive Therapy (IPT) aims to reduce the development of active TB in patients with latent TB

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