title: Prevention of nevirapine-associated exanthema using slow dose escalation and/or corticosteroids.
abstract: OBJECTIVE
  The appearance of rash is one of the most frequent and limiting side-effects during the first 4 weeks of treatment with nevirapine (NVP). We explored the efficacy and safety of four different strategies for reducing the incidence of this complication.
  
  
  METHODS
  Four-hundred and sixty-nine patients were assigned randomly to accomplish the induction phase of NVP following either the standard recommendation of 200 mg daily during the first 2 weeks (n = 166), or any of three new strategies: adding prednisone 50 mg each other day during the first 2 weeks (n = 93); using a slowly escalating dose, beginning with 100 mg daily the first week, and increasing the dose by 100 mg/week up to the full daily dose of 400 mg (n = 107); and combining both the addition of prednisone with the slowly escalating dose (n = 103). A pharmacokinetic substudy was performed in seven patients receiving 100 mg of NVP during the first week.
  
  
  RESULTS
  The incidence of rash diminished from 18.7% using the standard recommendation to 9.2% using the alternative approaches (P = 0.003). Rash appeared in 11.2%, 8.6%, and 7.7% of subjects assigned to receive the slowly escalating dose, prednisone, or both, respectively, without significant differences among them. The rate of drug discontinuation was also diminished by one-half using the new approaches (8.5% versus 4.3%; P = 0.06). NVP plasma concentrations within the first week of treatment using 100 mg daily were above the 90% inhibitory concentration for wild-type HIV-1 in all instances.
  
  
  CONCLUSIONS
  The incidence of rash complicating the first few weeks of treatment with NVP can be diminished by adding corticosteroids for 2 weeks to the standard recommendation, or by using a slowly escalating dose. This second approach is proven to be pharmacokinetically safe.
authors.affiliation: Service of Infectious Diseases, Hospital Carlos III, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Barreiro
authors.forename: V
authors.initials: V
authors.lastname: Soriano
authors.forename: E
authors.initials: E
authors.lastname: Casas
authors.forename: V
authors.initials: V
authors.lastname: Estrada
authors.forename: M J
authors.initials: MJ
authors.lastname: Téllez
authors.forename: R
authors.initials: R
authors.lastname: Hoetelmans
authors.forename: D G
authors.initials: DG
authors.lastname: de Requena
authors.forename: I
authors.initials: I
authors.lastname: Jimenéz-Nácher
authors.forename: J
authors.initials: J
authors.lastname: González-Lahoz
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005076:Exanthema / Q000139:chemically induced / Q000517:prevention & control*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects*; D011241:Prednisone / Q000627:therapeutic use*; D011446:Prospective Studies
chemical_list: D019380:Anti-HIV Agents; D000893:Anti-Inflammatory Agents; D019829:Nevirapine; D011241:Prednisone