title: Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy.
abstract: BACKGROUND
  This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc).
  
  
  METHODS
  Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission.
  
  
  RESULTS
  Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13).
  
  
  CONCLUSIONS
  Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.
authors.affiliation: HIV Monitoring Foundation, The Netherlands.
authors.forename: Anouk M
authors.initials: AM
authors.lastname: Kesselring
authors.forename: Ferdinand W
authors.initials: FW
authors.lastname: Wit
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Julio S
authors.initials: JS
authors.lastname: Montaner
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine