Insufficient tuberculosis treatment leads to earlier and higher mortality in individuals co-infected with HIV in Southern China: A cohort study

Abstract

Background: Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are the leading causes of death globally. However, little is known about the long-term mortality risk and 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, timeline of death in those with HIV-mycobacterium tuberculosis (MTB) coinfection, particularly in those TB treatment are insufficient.

Methods: TB-cause specific deaths, 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. The changes of 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 model was used to estimate the mean mortality at each time-point and change between time-points. Cox’s proportional hazard regression 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 followed-up.

Results: At the end point, mortality among HIV/MTB coinfection was 34.7%. From the end of TB treatment to PTY5, mortality of percentage and of person year in individuals with TBFMA were significant higher than those with TBC and TBCR. Compared to individuals with TBC and with TBCR, individuals with TBFMA were tend to die earlier, mortality was significantly higher (HR TBFMA-TBC = 3.0, 95% confidence interval: 2.5-3.6, HR TBFMA-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 significant higher across all stratifications except those with a CD4 count of ≤200 cells/μL.

Conclusions: Earlier and long-term mortality of HIV/MTB co-infection is a significant problem when TB treatment fails or is inadequate.