Is there cross-toxicity between nevirapine and efavirenz in subjects developing rash?

We read with interest the letter from Podzamczer et al. [1], in which the authors described two HIV-infected individuals who were able to tolerate efavirenz (EFV) after having developed a severe hypersensitivity reaction during a previous exposure to nevirapine (NVP). The authors noted that the concomitant administration of corticosteroids probably explained the good tolerability of EFV in these individuals. Although hypersensitivity reactions can develop with both NVP and EFV [2,3], to our knowledge there is no information on the risk of cross-toxicity between these two drugs. Despite the fact that they both belong to the non-nucleoside reverse transcriptase inhibitor family and act similarly, their molecular structure is not related, NVP being a member of the dipyridodiazepinone class and EFV a trifluoroderivate [4]. We have reviewed the experience accumulated with EFV in our institution during the Expanded Access Program. A total of 250 individuals were included between October 1998 and September 1999. All were adults, with a previous exposure to multiple antiretroviral drugs, being currently under virological failure, and having had a CD4 cell count below 400 cells/ml at any time in the past. All patients were instructed on the symptoms potentially related to EFV administration, and the incidence of side-effects was recorded prospectively after beginning the drug, which in all instances was used as part of a combination. Overall, side-effects of grade two or more in the World Health Organization (WHO) scale were recorded in 33 (13.2%) subjects, and in 17 (6.8%) the drug needed to be discontinued. Neurological abnormalities and dermatological toxicity were the most frequent side-effects (WHO grade ≥ 2), and were recorded in 24 and eight individuals, respectively. Of interest was the fact that only one out of eight subjects who had had NVP-associated rash developed exanthema after beginning EFV. Therefore, in our experience there is minor cross-toxicity between NVP and EFV with respect to hypersensitivity reactions. EFV can thus be safety administered to patients with a past history of hypersensitivity reactions with NVP. Vincent Soriano Carmen Dona Pablo Barreiro Juan González-Lahoz