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Meta-Analysis
. 2017 Jun;72(6):559-575.
doi: 10.1136/thoraxjnl-2016-209421. Epub 2017 Jan 23.

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis

P J Dodd  1 , A J Prendergast  2   3 , C Beecroft  1 , B Kampmann  4   5 , J A Seddon  4
Affiliations
Meta-Analysis

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis

P J Dodd et al. Thorax. 2017 Jun.

Abstract

Background: Children (<15 years) are vulnerable to TB disease following infection, but no systematic review or meta-analysis has quantified the effects of HIV-related immunosuppression or antiretroviral therapy (ART) on their TB incidence.

Objectives: Determine the impact of HIV infection and ART on risk of incident TB disease in children.

Methods: We searched MEDLINE and Embase for studies measuring HIV prevalence in paediatric TB cases ('TB cohorts') and paediatric HIV cohorts reporting TB incidence ('HIV cohorts'). Study quality was assessed using the Newcastle-Ottawa tool. TB cohorts with controls were meta-analysed to determine the incidence rate ratio (IRR) for TB given HIV. HIV cohort data were meta-analysed to estimate the trend in log-IRR versus CD4%, relative incidence by immunological stage and ART-associated protection from TB.

Results: 42 TB cohorts and 22 HIV cohorts were included. In the eight TB cohorts with controls, the IRR for TB was 7.9 (95% CI 4.5 to 13.7). HIV-infected children exhibited a reduction in IRR of 0.94 (95% credible interval: 0.83-1.07) per percentage point increase in CD4%. TB incidence was 5.0 (95% CI 4.0 to 6.0) times higher in children with severe compared with non-significant immunosuppression. TB incidence was lower in HIV-infected children on ART (HR: 0.30; 95% CI 0.21 to 0.39). Following initiation of ART, TB incidence declined rapidly over 12 months towards a HR of 0.10 (95% CI 0.04 to 0.25).

Conclusions: HIV is a potent risk factor for paediatric TB, and ART is strongly protective. In HIV-infected children, early diagnosis and ART initiation reduces TB risk.

Trial registration number: CRD42014014276.

Keywords: Tuberculosis.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Review and Meta-Analyses flow chart for systematic review (*one study included both a TB and HIV cohort17).
Figure 2
Figure 2
Forest plot for meta-analysis of HIV risk in children aged <15 years with prevalent TB—studies with controls (I2=69.8%). RE, random effects.
Figure 3
Figure 3
Forest plot for Bayesian meta-analysis of HIV risk in children aged <15 years with prevalent TB. Where studies lacked their own controls, UNAIDS national HIV prevalence data were used to model HIV prevalence in controls based on those studies with both controls and UNAIDS estimates (red). Meta-analyses for studies with controls only are shown in blue; meta-analyses for studies using UNAIDS estimates of paediatric HIV prevalence are shown in red.
Figure 4
Figure 4
Relative TB incidence in children aged <15 years with HIV by WHO immunological staging (I2=87.1%).
Figure 5
Figure 5
Forest plot for meta-analysis of relation between incidence rate ratio for TB incidence and CD4% in children aged <15 years.
Figure 6
Figure 6
Forest plot of protection on antiretroviral therapy against TB incidence in children <15 years with HIV infection (I2=79.0%). RE, random effects.
Figure 7
Figure 7
Meta-regression of protection from TB incidence in children <15 years by time-on-antiretroviral therapy (ART), and realigned incidence estimates from studies.
See this image and copyright information in PMC

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