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 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.

Methods: TB-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.

Results: At 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 (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 significantly higher across all stratifications except those with a CD4 count of ≤200 cells/μL.

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

Fig. 1

Study profile diagram showed how the study targets were selected and followed-up

Fig. 2

Mean mortality with ±95% confidence interval (CI) for person years of followed-up at the end of TB treatment (6 M), post-treatment year 1 (12 M), post-treatment year 2 (24 M), post-treatment year 3 (36 M), post-treatment year 4 (48 M), and post-treatment year 5 (60 M) among HIV/MTB coinfection patients treated with tuberculosis cure (TBC) (n = 680), tuberculosis complete regimen (TBCR) (n = 1289), and tuberculosis treatment failure, patients missing, adverse events (TBFMA) (n = 382) in Southern China

Fig. 3

Density of mortality at the end of TB treatment (0.5 PYs), post-treatment year 1 (1 PYs), post-treatment year 2 (2 PYs), post-treatment year 3 (3 PYs), post-treatment year 4 (4 PYs), and post-treatment year 5 (5 PYs) among HIV/MTB coinfection patients treated with tuberculosis cure (TBC) (n = 680), tuberculosis complete regimen (TBCR) (n = 1289), and tuberculosis treatment failure, patients missing, adverse events (TBFMA) (n = 382) in Southern China

Fig. 4

-1 and Fig. 4–2 Crude (4–1) and adjusted (4–2) accumulative Survival Function for mortality hazard risk at the end of TB treatment (6 months), post-treatment year 1 (12 M), post-treatment year 2 (24 M), post-treatment year 3 (36 M), post-treatment year 4 (48 M), and post-treatment year 5 (60 M) among HIV/MTB coinfection patients treated with tuberculosis cure (TBC) (n = 680), tuberculosis complete regimen (TBCR) (n = 1289), and tuberculosis treatment failure, patients missing, adverse events (TBFMA) (n = 382) in Southern China. Fig. 4–3 and Fig. 4–4 Adjusted accumulative Survival Function for mortality hazard risk at the end of TB treatment (6 months), post-treatment year 1 (12 M), post-treatment year 2 (24 M), post-treatment year 3 (36 M), post-treatment year 4 (48 M), and post-treatment year 5 (60 M) between stratifications of antiretroviral therapy (n = 362) and of antiretroviral therapy naïve (255) HIV/MTB coinfection patients treated with tuberculosis cure (TBC) (n = 680), tuberculosis complete regimen (TBCR) (n = 1289), and tuberculosis treatment failure, patients missing, adverse events (TBFMA) (n = 382) in Southern China