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Abstract
BackgroundTuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of death globally. However, little is known about the long-term mortality risk and the timeline of death in those co-infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB). This study sought to understand the long-term mortality risk, factors, and the timeline of death in those with HIV-Mycobacterium tuberculosis (MTB) coinfection, particularly in those with insufficient TB treatment.MethodsTB-cause specific deaths were classified using a modified ‘Coding of Cause of Death in HIV’ protocol. A longitudinal cross-registration-system checking approach was used to confirm HIV/MTB co-infection between two observational cohorts. Mortality from the end of TB treatment (6 months) to post-treatment year (PTY) 5 (60 months) was investigated by different TB treatment outcomes. General linear models were used to estimate the mean mortality at each time-point and change between time-points. Cox’s proportional hazard regressions measured the mortality hazard risk (HR) at each time-point. The Mantel-Haenszel stratification was used to identify mortality risk factors. Mortality density was calculated by person year of follow-up.ResultsAt the end point, mortality among patients with HIV/MTB coinfection was 34.7%. From the end of TB treatment to PTY5, mortality and loss of person years among individuals with TB treatment failure, missing, and adverse events (TBFMA) were significantly higher than those who had TB cure (TBC) and TB complete regimen (TBCR). Compared to individuals with TBC and with TBCR, individuals with TBFMA tended to die earlier and their mortality was significantly higher (HRTBFMA-TBC = 3.0, 95% confidence interval: 2.5–3.6, HRTBFMA-TBCR = 2.9, 95% CI: 2.5–3.4, P < 0.0001). Those who were naïve to antiretroviral therapy, were farmers, had lower CD4 counts (≤200 cells/μL) and were ≥ 50 years of age were at the highest risk of mortality. Mortality risk for participants with TBFMA was significantly higher across all stratifications except those with a CD4 count of ≤200 cells/μL.ConclusionsEarlier and long-term mortality among those with HIV/MTB co-infection is a significant problem when TB treatment fails or is inadequate.
Highlights
Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of death globally
Study subject characteristics Two thousand three fifty-one Mycobacterium tuberculosis (MTB)/human immunodeficiency virus (HIV) co-infections were confirmed among 42,205 TB registered cases in 2011, and HIV prevalence among those with TB was 5.6% (2351/42,205); a total of 2579.7 years was provided for the tuberculosis cure (TBC) group at the follow-up assessment, 4872.8 years for the tuberculosis complete regimen (TBCR) group, and 913.5 years for the TBFMA group over the 60-month follow-up period (Fig. 1)
The median (M) time participants were tracked at follow-up for the TBC group was 5.0 person-years (PYs), and the inter-quartile range (IQR) was 2.2–5.0; the M (IQR) for TBCR and TBFMA groups was 5.0 PYs (2.1–5.0) and 1.1 (0.3–5.0), respectively (Supplemental Fig. 1)
Summary
Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of death globally. Little is known about the long-term mortality risk and the timeline of death in those co-infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB). In 2010, WHO updated ART guidelines for HIV infection adults and adolescents, recommending that ART for all HIV-infected individuals with active TB, irrespective of their CD4 + T cell (CD4) count and that TB treatment should start first, followed by ART as quickly as possible afterward [7]. Following these guidelines, ART coverage improved rapidly worldwide; with 85% on ART [1]. Despite recommending ART and antitubercular therapy among patients presenting with TB and HIV, mortality associated with both diseases remains substantial [8] and the goal of halving TB-related deaths from 1990 levels by 2015 in high HIV/MTB coinfection prevalence countries has not been met
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