HIV co-infection increases the risk of post-tuberculosis mortality among persons who initiated treatment for drug-resistant tuberculosis

Abstract

Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant and multi/extensively drug-resistant (RR and M/XDR) TB reported to the country of Georgia's TB surveillance during 2009-2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia's death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) died during treatment and 87 (8.7%) died post-TB treatment. Among those who died post-TB treatment, the median time to death was 21 months (interquartile range 7-39) post-TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR=3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first three years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates.

Keywords: HIV co-infection; comorbidities; diabetes; hepatitis C; post-TB mortality; tuberculosis.

Figure 1. Participants selection according to inclusion criteria

This flowchart depicts the participants’ selection according to inclusion criteria (i.e., non-pediatric TB individuals with no prior history of TB treatment). Individuals were excluded if they had no pulmonary involvement, culture confirmation at the beginning of TB treatment, or unknown vital status during and after TB treatment.

Figure 2. Trend of mortality rates reported during and after TB treatment stratified by comorbidity status among persons who initiated treatment for RR or M/XDR TB in the country of Georgia from 2009 – 2017

Mortality rates during and post-TB treatment were estimated by 6-month period by building independent life tables. Mortality rates during and post-TB treatment were expressed per 1,000 populations. Mortality rates were then plotted continuously with a single interruption point to mark the end of TB treatment (red dashed line). The beginning of survival time of ‘TB treatment phase’ (T_0-treatment) marks the TB treatment initiation date. Thus, the point at T₆ in the ‘TB treatment’ phase indicates the mortality rate at 6-month after TB treatment initiation. The beginning of survival time of ‘Post-TB treatment’ phase (T_{0-post-TB treatment}) marks the end of TB treatment (i.e., could be treatment completion or lost to follow-up dates). Thus, the point at T₆ in the ‘Post-TB treatment’ phase indicates the mortality rate at 6-month after TB treatment ended.