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.
Patients and 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.
Conclusion: 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.