The Effect of Tuberculosis on Mortality in HIV Positive People: A Meta-Analysis

Masja Straetemans,Ana L Bierrenbach,Philippe Glaziou,Nico Nagelkerke,Marieke J Van Der Werf,Madhukar Pai

doi:10.1371/journal.pone.0015241

Abstract

BackgroundTuberculosis is a leading cause of death in people living with HIV (PLWH). We conducted a meta analysis to assess the effect of tuberculosis on mortality in people living with HIV.MethodsMeta-analysis of cohort studies assessing the effect of tuberculosis on mortality in PLWH. To identify eligible studies we systematically searched electronic databases (until December 2008), performed manual searches of citations from relevant articles, and reviewed conference proceedings. Multivariate hazard ratios (HR) of mortality in PLWH with and without tuberculosis, estimated in individual cohort studies, were pooled using random effect weighting according to “Der Simonian Laird method” if the p-value of the heterogeneity test was <0.05.ResultsFifteen cohort studies were systematically retrieved. Pooled overall analysis of these 15 studies estimating the effect of tuberculosis on mortality in PLWH showed a Hazard Ratio (HR) of 1.8 (95% confidence interval (CI): 1.4–2.3). Subanalysis of 8 studies in which the cohort was not exposed to highly active antiretroviral therapy (HAART) showed an HR of 2.6 (95% CI: 1.8–3.6). Subanalysis of 6 studies showed that tuberculosis did not show an effect on mortality in PLWH exposed to HAART: HR 1.1 (95% CI: 0.9–1.3).ConclusionThese results provide an indication of the magnitude of benefit to an individual that could have been expected if tuberculosis had been prevented. It emphasizes the need for additional studies assessing the effect of preventing tuberculosis or early diagnosis and treatment of tuberculosis in PLWH on reducing mortality. Furthermore, the results of the subgroup analyses in cohorts largely exposed to HAART provide additional support to WHO's revised guidelines, which include promoting the initiation of HAART for PLWH co-infected with tuberculosis. The causal effect of tuberculosis on mortality in PLWH exposed to HAART needs to be further evaluated once the results of more cohort studies become available.

Highlights

People living with HIV (PLWH) are estimated to have a 20 times higher risk on developing tuberculosis (TB) disease compared to people living without human immunodeficiency virus (HIV) infection in countries with an HIV prevalence of at least 1%.[1]
In 9 studies TB was defined as sputum smear positive confirmed by culture or clinical and radiologic improvement after TB treatment, in a patient with clinical signs and symptoms consistent with active TB. [11,20,22,28,21,26,27,29,31] In 2 studies TB was primarily diagnosed by sputum smear examination and clinical symptoms and/or radiological abnormalities without culture confirmation. [8,16] people living with HIV (PLWH) with prior TB diagnosis were excluded from participation in five studies [11,20,22,28,29] while in nine studies TB history was not an exclusion criteria [8,16,17,19,24,25,27,31,33] and one study did not report on TB history.[26]
TB had a large effect on mortality in PLWH participating in a study conducted before highly active antiretroviral therapy (HAART) was available: hazard ratios (HR) 2.6. (Table 1, Analyses 5.1) When including one study that was conducted during the HAART era but of which less than 10% of the cohort had been exposed to HAART resulted in a similar HR: 2.6 (Figure 5)

Summary

Introduction

People living with HIV (PLWH) are estimated to have a 20 times higher risk on developing tuberculosis (TB) disease compared to people living without human immunodeficiency virus (HIV) infection in countries with an HIV prevalence of at least 1%.[1] Fifteen percent of the incident TB cases in 2008 are estimated to be co-infected with human immunodeficiency virus (HIV).[1] TB is the leading direct cause of death among PLWH in Africa and a major cause of death elsewhere.[2,3] The estimated number of incident TB cases in PLWH was 1.4 million in 2008 (range 1.3–1.5 million). Tuberculosis is a leading cause of death in people living with HIV (PLWH).

Methods

Results

Discussion

Conclusion