Incidence and mortality of tuberculosis before and after initiation of antiretroviral therapy: an HIV cohort study in India

Gerardo Alvarez-Uria, Raghavakalyan Pakam, Manoranjan Midde, Praveen K Naik, Gerardo Alvarez-Uria, Raghavakalyan Pakam, Manoranjan Midde, Praveen K Naik

Abstract

Introduction: India has the highest burden of tuberculosis (TB) in the world, but the epidemiology of HIV-associated TB is not well known.

Methods: We describe the incidence and the mortality of TB from HIV diagnosis to antiretroviral therapy (ART) initiation (pre-ART group) and after ART initiation (on-ART group) in an HIV cohort study in Anantapur, India. Multivariable analysis of factors associated with TB was performed using competing risk regression and restricted cubic spline methods.

Results: A total of 4590 patients and 3133 person-years (py) of follow-up were included in the pre-ART group, and 3784 patients and 4756 py were included in the on-ART group. In the pre-ART group, the incidence of TB was high during the first month after HIV diagnosis and dropped nearly four times soon after. In the on-ART group, the incidence of TB increased after ART initiation reaching a peak in the third month. The probability of having TB within 30 months was 22.3% (95% confidence interval [CI], 21.1-23.6) in the pre-ART group and 17.8% (95% CI, 16.3-19.3) in the on-ART group. In a multivariable analysis, women had a lower risk of TB in both groups. Poor socio-economical conditions were associated with an increased risk of TB in the pre-ART group, but not in the group on-ART. While the association between low CD4 counts and TB was strong in the pre-ART group, this association was weaker in the on-ART group, and the highest risk of TB was seen in those patients with CD4 counts around 110 cells/mm3. The cumulative incidence of mortality at 12 months in patients with TB was 29.6% (95% CI, 26.9-32.6) in pre-ART TB and 34.9% (95% CI, 31-39.1) in on-ART TB. Half deaths before ART initiation and two thirds of deaths after ART initiation occurred in patients with TB.

Conclusions: The high incidence and mortality of TB seen in this study underscore the urgent need to improve the prevention and diagnosis of HIV-associated TB in India. We found substantial differences between TB before and after ART initiation.

Keywords: CD4 lymphocyte count; HIV; India; antiretroviral therapy; gender; incidence; mortality; risk; rural; tuberculosis.

Figures

Figure 1
Figure 1
Risk of tuberculosis (TB) with 95% confidence intervals according to time-updated CD4+ lymphocyte counts from HIV diagnosis to antiretroviral therapy (ART) initiation and after ART initiation.
Figure 2
Figure 2
Risk of tuberculosis (TB) with 95% confidence intervals according to baseline age from HIV diagnosis to antiretroviral therapy (ART) initiation and after ART initiation.
Figure 3
Figure 3
Kernel smoothed hazard of tuberculosis (TB) with 95% confidence intervals from HIV diagnosis to antiretroviral therapy (ART) initiation and after ART initiation.
Figure 4
Figure 4
Cumulative incidence of tuberculosis (TB) with 95% confidence intervals from HIV diagnosis to antiretroviral therapy (ART) initiation and after ART initiation.
Figure 5
Figure 5
Cumulative incidence of mortality with 95% confidence intervals in patients with tuberculosis (TB) before and after antiretroviral therapy (ART) initiation.
Figure 6
Figure 6
Mortality risk with 95% confidence intervals according to time-updated CD4+ lymphocyte counts of patients with tuberculosis (TB) before and after antiretroviral therapy (ART) initiation.
Figure 7
Figure 7
Mortality risk with 95% confidence intervals according to timing of tuberculosis (TB) diagnosis of patients with TB before and after antiretroviral therapy (ART) initiation.
Figure 8
Figure 8
Stacked graphs of the status of patients from HIV diagnosis to antiretroviral therapy (ART) initiation and after ART initiation.

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