High incidence of nevirapine-associated rash in HIV-infected Chinese

Rash is a common side-effect of nevirapine, a non-nucleoside reverse transcriptase inhibitor. The incidence of rash associated with the use of nevirapine has varied across different studies [^1-5], being cited at 17% by the manufacturer (Viramune package insert; Roxane Laboratories, Inc., Columbus, Ohio, USA). Stevens-Johnson syndrome has also occurred in 0.5-1% of patients [^5,6]. Most of the study subjects in trials of nevirapine were Caucasians [^1,2,4]. Experience in our local Chinese patients showed an exceptionally high incidence of rash related to the use of this drug.

Amongst the Chinese HIV-positive patients who had been observed for 8 weeks or more after commencing treatment with nevirapine, five (62.5%) out of eight patients had developed skin rash. The skin eruption occurring in our patients was a generalized, maculopapular rash, affecting the face, trunk and limbs. Fever was present in two patients. Although none had mucosal involvement, the rash was severe enough to warrant withholding nevirapine in all patients, after failure to improve on oral antihistamine. All resolved promptly upon withdrawal of the drug. None of the patients were rechallenged.

Nevirapine was given as part of triple therapy in all eight patients, either with zidovudine-didanosine or stavudine-didanosine. None had any history of drug allergy. All patients had a lead-in period of 14 days during which 200 mg nevirapine was given once daily, a dosage recommended to lessen the frequency of rash (Viramune package insert; Roxane Laboratories). In one patient the rash appeared after 11 days of treatment. For the other patients, the rash began in weeks 3 and 4 of treatment, when the dosage of nevirapine was increased to 200 mg twice daily.

Liver function tests were checked for four of the five patients at the time of rash. Three patients had raised enzyme levels compared with their normal prenevirapine baseline. Their alanine aminotransferase level ranged from 93 to 266 U/l, alkaline phosphatase from 48 to 608 U/l, and total bilirubin from 22 to 124 μmol/l. For the fourth patient, liver function did not show any deterioration from a midly abnormal baseline.

The median CD4 cell count in the five patients who developed rash was 229 × 10⁶/l, comparable to the CD4 cell count of 284 × 10⁶/l in the other three patients who did not have rash within the first 8 weeks of treatment. Three patients in the first group were men, whereas all were men in the latter group. Median body weights were 62.0 and 69.3 kg, respectively. Three patients who developed rash were treatmentnaive, compared with two out of those who did not have rash. For the other patients, nevirapine was added to the pre-existing regimen as consolidation of treatment.

It is unlikely that the rash was related to the nucleoside analogues rather than to nevirapine. Zidovudine, didanosine and stavudine have been extensively used in our local patients and drug rash had been a rare event.

In summary, a high incidence of hypersensitivity reaction had been observed among Chinese patients treated with nevirapine. Whether there is any definite association has yet to be proven. Physicians, meanwhile, should be cautioned about this problem when prescribing nevirapine to their Chinese HIV-positive patients.