title: Safety and efficacy of once-daily nevirapine dosing: a multicohort study.
abstract: BACKGROUND
  Nevirapine (NVP) is often prescribed once daily in clinical practice in combination with a once daily nucleoside backbone. We investigated the relationship of NVP dosing with safety and efficacy.
  
  
  METHODS
  Patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort study, Canadian HAART Observational Medical Evaluation and Research (HOMER) cohort and Swiss HIV Cohort Study (SHCS) using NVP-based combination therapy either once daily or twice daily were included. Risk factors for discontinuing NVP because of hypersensitivity reactions (HSRs) were investigated using multivariate logistic regression. Risk factors for virological failure 96 weeks after NVP initiation were identified using logistic regression and Cox models.
  
  
  RESULTS
  Of 5,636 patients (774 once daily and 4,862 twice daily), 268 (4.8%) discontinued NVP because of HSR between 2 and 18 weeks. Logistic regression showed that, compared with patients with detectable HIV type-1 (HIV-1) RNA starting twice-daily NVP, there was a significantly higher risk of discontinuation of once-daily NVP because of HSR in patients with detectable HIV-1 RNA at the start of NVP (odds ratio [OR] 1.52; P=0.04), whereas the risk was actually significantly lower in patients starting once-daily NVP with undetectable HIV-1 RNA (OR 0.44; P=0.04). Cox models showed that risk of virological failure was not different for twice- versus once-daily NVP in treatment-naive patients (twice-daily versus once-daily hazard ratio [HR] 1.01; P=0.95), treatment-experienced patients experiencing treatment failure (twice-daily versus once-daily HR 1.22; P=0.30) or patients with undetectable HIV-1 RNA simplifying treatment with NVP (twice-daily versus once-daily HR 1.29; P=0.30).
  
  
  CONCLUSIONS
  Initiation of a once-daily NVP-based regimen in patients with suppressed viraemia carries a low risk of treatment-limiting HSR. Once- or twice-daily NVP-based regimens appear to have similar antiretroviral efficacy.
authors.affiliation: Division of Infectious Disease/HIV unit, University Hospital Geneva, Geneva, Switzerland. acalmy@gmail.com
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vallier
authors.forename: Alain
authors.initials: A
authors.lastname: Nguyen
authors.forename: Joep Ma
authors.initials: JM
authors.lastname: Lange
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Viviane D
authors.initials: VD
authors.lastname: Lima
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hogg
authors.forename: Benita
authors.initials: B
authors.lastname: Yip
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: Ferdinand W
authors.initials: FW
authors.lastname: Wit
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D063065:Organophosphonates / Q000627:therapeutic use; D012189:Retrospective Studies; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D019829:Nevirapine; D000068698:Tenofovir; D000225:Adenine