Journal Article

Acquired Rifampicin Resistance in Thrice-Weekly Antituberculosis Therapy: Impact of HIV and Antiretroviral Therapy

Kumar, Santhanakrishnan Ramesh, Padmapriyadarsini, Chandrasekaran, Menon, Pradeep Aravindan, Vijay, Krishnamoorthy, Narendran, Gopalan, Bhavani, Kannabiran Perumal, Gomathi, Sivaramakrishnan Narayan, Chandrasekhar, Chockalingam, Sridhar, Rathinam, Swaminathan, Soumya, Kumar, Satagopan, Venkatesan, Perumal, Sekar, Lakshmanan

2014

Overview

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 antituberculosis 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/μL, 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], 1.7–14.8; P < .0001) and 2.1 (95% CI, .9–5.2; P = .3), whereas for ARR, the RRs were 21.1 (95% CI, 2.6–184; P < .001) and 8.2 (95% CI, .6–104; P = .07), respectively. Conclusions. HIV-infected patients with tuberculosis treated with a thrice-weekly antituberculosis 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.

• Publisher: Oxford University Press
• Subject: Adolescent / Adult / AIDS / Antibacterial agents / Antibiotics / Antibiotics. Antiinfectious agents. Antiparasitic agents / Antiretroviral agents / Antiretroviral drugs / Antiretroviral Therapy, Highly Active / Antitubercular Agents - therapeutic use / Antiviral agents / Biological and medical sciences / Clinical trials / Drug resistance / Drug Resistance, Bacterial - drug effects / Female / Health outcomes / Highly active antiretroviral therapy / HIV / HIV infections / HIV Infections - complications / HIV Infections - drug therapy / HIV/AIDS / Human immunodeficiency virus / Human viral diseases / Humans / Impact analysis / Infectious diseases / Male / Medical sciences / Pharmacology. Drug treatments / Predisposing factors / Pulmonary tuberculosis / Regression analysis / Rifampin - therapeutic use / Risk Factors / Sputum / Tuberculosis / Tuberculosis - drug therapy / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Young Adult