title: Efavirenz trough levels are not associated with virological failure throughout therapy with 800 mg daily and a rifampicin-containing antituberculosis regimen.
abstract: OBJECTIVE
  To assess the safety and efficacy of efavirenz 800 mg daily in HIV-infected patients with tuberculosis receiving a rifampicin-containing regimen and to analyse whether a relationship exists between efavirenz Cmin and its virological efficacy.
  
  
  METHODS
  Prospective, open-labelled study including HIV-infected patients on rifampicin and efavirenz 800 mg daily. Treatment adherence, adverse events (AEs), HIV-RNA levels, CD4 cell counts and efavirenz Cmin during and after finishing rifampicin treatment were evaluated.
  
  
  RESULTS
  Eighty patients met the inclusion criteria. A permanent drug withdrawal due to AEs occurred in 10 patients, 5 attributable to efavirenz, and 10 patients were lost to follow-up before the third month. Efavirenz Cmin levels with 800 mg plus rifampicin were similar to those with 600 mg after withdrawing rifampicin. Sixty patients were included in the efficacy analysis, eight experiencing virological failure. No relation was observed between the rate of virological failure and efavirenz Cmin, previous antiretroviral treatment or not, baseline CD4 counts or RNA-HIV. The only variable related to virological failure was irregular adherence [odds ratio, 81 (95% CI: 5-1280); P=0.002].
  
  
  CONCLUSIONS
  Given the lack of a demonstrated relationship between efavirenz Cmin and its efficacy in our study, a firm recommendation cannot be made to always increase the dose to 800 mg/day when concomitantly given with rifampicin, but it seems a cautious approach to maintain the same efavirenz plasma levels as with 600 mg daily without rifampicin. Patients weighing<55 kg and also black, Asian and Hispanic subjects in whom genetic-based increased efavirenz plasma levels and rates of AEs have been observed may benefit from a dose of 600 mg.
authors.affiliation: Infectious Diseases Service, Hospitales Universitarios, Virgen del Rocío, Seville, Spain. lflopez@telefonica.net
authors.forename: Luis F
authors.initials: LF
authors.lastname: Lopez-Cortes
authors.forename: Rosa
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: Josefa
authors.initials: J
authors.lastname: Ruiz-Morales
authors.forename: Eva
authors.initials: E
authors.lastname: Leon
authors.forename: Antonio Vergara
authors.initials: AV
authors.lastname: de Campos
authors.forename: Ana
authors.initials: A
authors.lastname: Marin-Niebla
authors.forename: Manuel
authors.initials: M
authors.lastname: Marquez-Solero
authors.forename: Fernando
authors.initials: F
authors.lastname: Lozano
authors.forename: Rebeca
authors.initials: R
authors.lastname: Valiente
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000009:adverse effects; D048588:Benzoxazines; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006678:HIV / Q000302:isolation & purification*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D010078:Oxazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000145:classification; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects; D014376:Tuberculosis / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz; D012293:Rifampin