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

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.

Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania

“…This high diversity of mutations among DR-TB patients suggests on-going transmission of MDR-TB strains rather than acquisition through random mutation and selection of drug resistance strains [37,39]. In addition, our analysis revealed a large deletion that involved Rv2044c in [40]. On the other hand, MTBC isolates from DS-TB participants had no mutations in genes encoding for INH, RIF, PZA, SM and EMB, which is in keeping with Cryptic consortium findings that reported susceptibility profiles for all isolates unless uncharacterized mutations or missing key nucleotide calls were present [41].…”

Infecção latente por tuberculose entre pessoas com HIV/AIDS, fatores associados e progressão para doença ativa em município no Sul do Brasil

“…Ressalta-se que 13 (19,7%) indivíduos com diagnóstico de ILTB evoluíram para TB ativa. Quando a terapia com isoniazida é adotada tem-se a redução substancial das chances de desenvolvimento da doença e do óbito 6,25,26 .…”

“…Interferindo nesses indicadores, muito provavelmente se contribuiria à mudança do cenário epidemiológico encontrado 25,29 .…”

Diagnosis and management of latent tuberculosis

“…Preventive therapy with INH is also effective in patients coinfected with HIV [44,45]. A recent meta-analysis of this population, including those on antiretroviral therapy (ART), confirmed the efficacy of INH therapy in preventing tuberculosis, particularly in those with positive TSTs [46]. INH is also effective in reducing progression of tuberculosis among HIV patients with negative TSTs, although the benefit is greatest among those with positive TSTs [47].…”