With the increasing coverage and a 2-4% rate of virologic failure on first line antiretroviral treatment (ART) regimens globally, the number of patients who will need second-line ART containing protease inhibitor (PI) based regimens is increasing. Tuberculosis (TB) continues to be the leading cause of opportunistic infection and death among HIV-infected patients. However data on the TB incidence and mortality among HIV-infected patients receiving second line ART regimens are limited.
Retrospective cohort analysis of 59691 HIV-infected patients was conducted between January 2006 and June 2014 from a large public sector ART center of Byramjee-Jeejeebhoy Medical College-Sassoon General Hospitals (BJMC-SGH), Pune, India. Inclusion criteria included patients receiving PI (boosted atazanavir or lopinavir)-based second line ART regimens. TB was diagnosed either clinically or microbiologically by acid-fast bacillus smear as per the national program guidelines. Study outcomes included estimates of TB incidence and case fatality rates among patients receiving second line ART. We conducted a Poisson regression analysis to assess independent predictors of TB disease.
The analyses included 405 patients on second line ART regimens who were followed for a median of 3.96 person-years (interquartile range (IQR), 2.23-5.28). Median age was 35 years (IQR, 31 – 40) and 138 (34%) were females. Median CD4 count at time of initiation of second line ART was 118 (IQR, 45 – 189) cells/cumm. TB incidence was 54.5 per 1000 person-years ((PY) 95% confidence interval (CI), 43.5 – 67.4). The median time to TB incidence was 1.92 (IQR, 1.04-2.93) PY. The risk factors for TB included male gender (adjusted incidence rate ratio (AIRR), 3.45, 1.33 – 9.09, p=0.01), and unit decrease in hemoglobin (AIRR, 1.17; 95% CI, 1.04 – 1.32, p = 0.009). All-cause case-fatality was 26.7 (95% CI, 8.7 – 62.3) /1000 PY among TB co-infected patients receiving 2nd line ART.
Our study documents a high TB incidence and mortality among patients receiving second line PI-based ART. Since the high TB incidence on second line ART pose treatment challenges due to drug interactions between rifampin and PIs, long recommended World Health Organization’s TB prevention strategies such as isoniazid prophylaxis need to be prioritized among all HIV-infected patients in India and other high TB burden countries.