title: Acquired rifampicin resistance in thrice-weekly antituberculosis therapy: impact of HIV and antiretroviral therapy.
abstract: 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.
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Gopalan
authors.initials: G
authors.lastname: Narendran
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Pradeep Aravindan
authors.initials: PA
authors.lastname: Menon
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Perumal
authors.initials: P
authors.lastname: Venkatesan
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Vijay
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Padmapriyadarsini
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Santhanakrishnan
authors.initials: S
authors.lastname: Ramesh Kumar
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Kannabiran Perumal
authors.initials: KP
authors.lastname: Bhavani
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Sekar
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Sivaramakrishnan Narayan
authors.initials: SN
authors.lastname: Gomathi
authors.affiliation: Government Hospital of Thoracic Medicine, Tambaram Sanatorium.
authors.forename: Chockalingam
authors.initials: C
authors.lastname: Chandrasekhar
authors.affiliation: Government Hospital of Thoracic Medicine, Tambaram Sanatorium.
authors.forename: Satagopan
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Government Stanley Hospital, Tondiarpet, Chennai, India.
authors.forename: Rathinam
authors.initials: R
authors.lastname: Sridhar
authors.affiliation: National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre), Chetpet.
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D012293:Rifampin / Q000627:therapeutic use*; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin
keywords: HIV; acquired rifampicin resistance; drug-resistant tuberculosis; intermittent therapy; tuberculosis