Incidence of tuberculosis in HIV-infected adults on first- and second-line antiretroviral therapy in India

Akshay N Gupte,Smita Nimkar,Shashikala Sangle,Bharat B Rewari,Sonali Salvi,Vidya Mave,Amita Gupta,Amol Chavan,Jonathan Golub,Ivan Marbaniang,Dileep Kadam,Nikhil Gupte

doi:10.1186/s12879-019-4569-z

Abstract

BackgroundProgrammatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India.MethodsWe estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India.Results4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86–5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01–2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02–1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13–2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58–5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen.ConclusionRisk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.

Highlights

Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India
Compared to participants on firstline anti-retroviral therapy (ART), those receiving second-line ART were older, more likely to be male (50% vs 65%), less like to live in an urban setting (71% vs 62%), more likely to have had Tuberculosis disease (TB) in the past (1% vs 3%) and had higher CD4+ cell counts at their respective ART initiation (p < 0.001 for all comparisons) (Table 1)
While our study results are consistent with prior reports of a switch to protease inhibitor (PI) based regimens reducing the incidence of opportunistic infections and mortality in PLHIV with virologic failure [11,12,13], a survivor bias likely to be present in those who initiated second-line ART after failing prior regimens, or a delay in switching to second-line ART may have contributed to our study findings

Summary

Introduction

Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. People living with HIV (PLHIV) are at high risk of developing TB and account for nearly 9% of new TB cases and nearly 300,000 TB-related deaths globally [1]. Widespread anti-retroviral therapy (ART) has significantly reduced the incidence of TB in PLHIV. To further reduce the burden of TB, the World Health Organization (WHO) recommends isoniazid prevention therapy (IPT) for all PLHIV in high TB-burden settings [4]. India has the third highest HIV burden and the highest TB burden globally with nearly one million new TB cases among PLHIV each year [5]. India’s National AIDS Control Organization (NACO) provides free firstand second-line ART, and has recommended IPT in all

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Discussion

Conclusion