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

• Published in: Clinical infectious diseases Vol. 59; no. 12; pp. 1798 - 1804
• Main Authors: Narendran, Gopalan, Menon, Pradeep Aravindan, Venkatesan, Perumal, Vijay, Krishnamoorthy, Padmapriyadarsini, Chandrasekaran, Kumar, Santhanakrishnan Ramesh, Bhavani, Kannabiran Perumal, Sekar, Lakshmanan, Gomathi, Sivaramakrishnan Narayan, Chandrasekhar, Chockalingam, Kumar, Satagopan, Sridhar, Rathinam, Swaminathan, Soumya
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15-12-2014
• Subjects: Adolescent; Adult; AIDS; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic 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; Immunopathology; Antiretroviral agent; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Resistance; Antibiotic; Chemotherapy; Treatment; Rifampicin; Viral disease; Antiviral; Antituberculous agent; Protein synthesis inhibitor; Human immunodeficiency virus; Antibacterial agent; intermittent therapy; HIV; acquired rifampicin resistance; drug-resistant tuberculosis; tuberculosis
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciu674

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.