Acquired Rifampicin resistance in thrice-weekly anti-tuberculosis therapy: Impact of HIV and antiretroviral therapy.


Narendran, G.; Menon, P.A.; Venkatesan, P.; Vijay, K.; Padmapriyadarsini, C.; Ramesh Kumar, S.; Bhavani, P.K.; Sekar L, Gomathi, N.S.; Chandrasekhar, C.; Kumar, S.; Sridhar, R.; Swaminathan, S.


Clinical Infectious Diseases; 2014; 59; 1798-1804.


Background: Risk factors for acquired rifampicin resistance (ARR) in human immunodeficiency virus (HIV)/tuberculosis coinfection, in the highly active antiretroviral therapy (HAART) era, needs evaluation. We studied the impact of HIV and HAART on ARR among patients taking thrice-weekly anti-tuberculosis therapy.


Methods: This cross-protocol analysis included patients with newly diagnosed, rifampicin-susceptible pulmonary tuberculosis, with and without HIV, enrolled in clinical trials (who took >80% of medication) at the National Institute for Research in Tuberculosis between 1999 and 2013. All patients received rifampicin and isoniazid for 6 months reinforced with pyrazinamide and ethambutol in the first 2 months, given thrice-weekly throughout the study along with HAART in one of the groups. Outcomes were categorized and multivariate logistic regression analysis performed to identify risk factors for ARR.


Results: The per-protocol results included patients with tuberculosis: 246 HIV-uninfected patients (HIV TB + ), 212 HIV patients not on HAART (non-HAART), and 116 HIV-infected patients on HAART. Median CD4 counts of the latter 2 groups were 150 and 93 cells/L, respectively, and the median viral loads were 147 000 and 266 000 copies/mL, respectively. Compared with HIV TB + , the relative risks (RRs) for an unfavorable response in the coinfected, non-HAART and HAART groups were 2.1 (95% confidence interval [CI], 1.714.8; P < .0001) and 2.1 (95% CI, .95.2; P = .3), whereas for ARR, the RRs were 21.1 (95% CI, 2.6184; P < .001) and 8.2 (95% CI, .6104; P = .07), respectively.


Conclusions: HIV-infected patients with tuberculosis treated with a thrice-weekly anti-tuberculosis regimen are at a higher risk of ARR, compared with HIV-uninfected patients, in the presence of baseline isoniazid resistance. HAART reduces but does not eliminate the risk of ARR.


Keywords: HIV; tuberculosis; drug-resistant tuberculosis; intermittent therapy; acquired rifampicin resistance.


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