TB pre- and post- antiretroviral therapy initiation in India

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

Alvarez-Uria G, Pakam R, Midde M, Naik PK. J Int AIDS Soc. 2014 Dec 9;17:19251. doi: 10.7448/IAS.17.1.19251. eCollection 2014.

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-economic 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.

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Editor’s notes: Although India has a huge burden of TB, there are relatively few published data regarding the epidemiology of HIV-associated TB, which this retrospective analysis begins to address. This study describes the incidence of TB and mortality among people with TB. The study looked at a cohort of people living with HIV, attending a rural hospital funded by a non-governmental organisation where medical care, including antiretroviral therapy and TB treatment, were provided free of charge. The authors report extremely high incidence of TB shortly after both HIV diagnosis and antiretroviral therapy initiation. They also report high mortality among individuals with TB, all of which are far greater than described in antiretroviral therapy programmes in South Africa. As the authors note, this likely reflects multiple issues. These include the fact that people often first present for HIV care due to symptoms of TB, unsatisfactory screening for TB, and inadequate investigation of individuals with TB symptoms, which relies on sputum microscopy and radiology. Furthermore, isoniazid preventive therapy is not yet implemented in India and the authors report that buildings designated as antiretroviral therapy centres are often inadequate in terms of infection control. This study highlights the urgency of comprehensive implementation of WHO’s three I’s (intensified case finding, isoniazid preventive therapy, infection control) for tuberculosis strategy in this setting and access to better, affordable and rapid diagnostic tests for TB.

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