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. 2017 Aug 29;8(8):CD006418.
doi: 10.1002/14651858.CD006418.pub3.

Isoniazid for preventing tuberculosis in HIV-infected children

Moleen Zunza  1 , Diane M Gray, Taryn Young, Mark Cotton, Heather J Zar
Affiliations

Isoniazid for preventing tuberculosis in HIV-infected children

Moleen Zunza et al. Cochrane Database Syst Rev. .

Abstract

Background: Tuberculosis (TB) is an important cause of illness and death in HIV-positive children living in areas of high TB prevalence. We know that isoniazid prophylaxis prevents TB in HIV-negative children following TB exposure, but there is uncertainty related to its role in TB preventive treatment in HIV-positive children.

Objectives: To summarise the effects of TB preventive treatment versus placebo in HIV-positive children with no known TB contact on active TB, death, and reported adverse events.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, Embase and two trial registers up to February 2017.

Selection criteria: We included trials of HIV-positive children with and without known TB exposure, randomized to receive TB preventive treatment or placebo.

Data collection and analysis: Two review authors independently used the study selection criteria, assessed risk of bias, and extracted data. We assessed effects using risk, incidence rate and hazard ratios and assessed the certainty of evidence using GRADE.

Main results: We included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow-up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART).In HIV-positive children not on ART, isoniazid prophylaxis may reduce the risk of active TB (hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.11 to 0.87; 1 trial, 240 participants, low certainty evidence), and death (HR 0.46, 95% CI 0.22 to 0.95; 1 trial, 240 participants, low certainty evidence). One trial (182 participants) reported number of children with laboratory adverse events, which was similar between the isoniazid prophylaxis and placebo groups. No clinical adverse events were reported.In HIV-positive children on ART, we do not know if isoniazid prophylaxis reduces the risk of active TB (risk ratio (RR) 0.76, 95% CI 0.50 to 1.14; 3 trials, 737 participants, very low certainty evidence) or death (RR 1.45, 95% CI 0.78 to 2.72; 3 trials, 737 participants, very low certainty evidence). Two trials (714 participants) reported number of clinical adverse events and three trials (795 participants) reported number of laboratory adverse events; for both categories, the number of adverse events were similar between the isoniazid prophylaxis and placebo groups.

Authors' conclusions: Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV-positive children not on ART in studies from Africa. For children on ART, no clear benefit was detected. .

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Conflict of interest statement

MZ: MZ is supported by the Effective Health Care Research Consortium funded by UK aid from the UK Government for the benefit of developing countries (Grant: 5242). The views expressed in this publication do not necessarily reflect UK government policy.

DG: Author of an included study

TY: TY is supported by the Effective Health Care Research Consortium funded by UK aid from the UK Government for the benefit of developing countries (Grant: 5242). The views expressed in this publication do not necessarily reflect UK government policy.

MC: Author of an included study

HZ: Author of an included study

To avoid potential bias, authors who were investigators on included studies did not do data extraction and methodological quality assessment of included studies.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
3
3
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 Isoniazid prophylaxis versus placebo, outcome: 1.1 Active TB, HIV‐positive children on ART.
5
5
Forest plot of comparison: 1 Isoniazid prophylaxis versus placebo, outcome: 1.2 Death, HIV‐positive children on ART.
1.1
1.1. Analysis
Comparison 1 Isoniazid prophylaxis versus placebo for HIV‐positive children on antiretroviral therapy (ART), Outcome 1 Active TB.
1.2
1.2. Analysis
Comparison 1 Isoniazid prophylaxis versus placebo for HIV‐positive children on antiretroviral therapy (ART), Outcome 2 Death.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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