title: Lack of association between plasma levels of non-nucleoside reverse transcriptase inhibitors & virological outcomes during rifampicin co-administration in HIV-infected TB patients.
abstract: OBJECTIVE
  Among patients with HIV-associated tuberculosis (TB), reduced plasma non-nucleoside reverse transcriptase inhibitors (NNRTI) concentrations during rifampicin (RMP) co-administration could lead to HIV treatment failure. This study was undertaken to examine the association between plasma nevirapine (NVP) and efavirenz (EFV) concentrations and virological outcomes in patients infected with HIV-1 and TB.
  
  
  METHODS
  This was a nested study undertaken in a clinical trial of patients with HIV-1 and TB, randomized to two different once-daily antiretroviral treatment (ART) regimens along with anti-TB treatment (ATT). Trough concentrations of plasma NVP and EFV were estimated at months 1 (during ATT and ART) and 6 months (ART only) by HPLC. Plasma HIV-1 RNA level >400 copies/ml or death within 6 months of ART were considered as unfavourable outcomes. Genotyping of CYP2B6 516G>T polymorphism was performed.
  
  
  RESULTS
  Twenty nine per cent of patients in NVP arm had an unfavourable outcome at 6 months compared to 9 per cent in EFV arm (P<0.08). The mean NVP and EFV levels estimated at 1 and 6 months did not significantly differ between favourable and unfavourable responders. Logistic regression analysis showed CYP2B6 516G>T polymorphism significantly associated with virologic outcome in patients receiving EFV-based regimen.
  
  
  CONCLUSIONS
  Trough plasma concentrations of NVP and EFV did not show any association with response to ART in patients on ATT and once-daily ART. CYP2B6 516G>T polymorphism was associated with virologic outcome among patients on EFV.
authors: Geetha
authors: G
authors: Ramachandran
authors: A K Hemanth
authors: AK
authors: Kumar
authors: C
authors: C
authors: Ponnuraja
authors: K
authors: K
authors: Ramesh
authors: Lakshmi
authors: L
authors: Rajesh
authors: C
authors: C
authors: Chandrasekharan
authors: National Institute for Research in Tuberculosis (ICMR), Chennai, India.
authors: Soumya
authors: S
authors: Swaminathan
mesh_terms: D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000008:administration & dosage / Q000097:blood; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood*; D012293:Rifampin / Q000008:administration & dosage* / Q000097:blood; D014376:Tuberculosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz; D012293:Rifampin