Rash no more frequent in Thais treated with NNRTIs than Caucasians

Rash appears to be no more frequent in Thai patients treated with standard doses of efavirenz or nevirapine than in Caucasians, according to an analysis of the 2NN study published in the January 25^th edition of AIDS.

Although NNRTIs are recommended for first-line treatment in resource-limited settings, the incidence of rash has not been established in Asian populations. Investigators for the 2NN study, which compared efavirenz and nevirapine-based regimens in first line treatment, accordingly carried out an analysis of the incidence of rash in 202 Thai patients who took part in the international study. The report does not compare the incidence of rash between Thai and Caucasian participants in the 2NN study, but instead uses historical data from registration studies of nevirapine and efavirenz.

The 2NN study compared once or twice daily nevirapine with once daily efavirenz or nevirapine and efavirenz dosed together once daily. All drugs were combined with stavudine (d4T, Zerit) and lamivudine (3TC, Epivir). Participants had no prior experience of antiretroviral treatment.

Numbers allocated to each study arm were: efavirenz 600mg qd (69); nevirapine 200mg bd (44); nevirapine 400mg qd (47); nevirapine 400mg qd plus efavirenz 800mg qd (42). Patients randomised to receive nevirapine 200mg bid or efavirenz 600mg qd had more advanced HIV disease, lower CD4 cell count and higher ALT (liver enzyme) than the other two arms.

Sixty-nine cases of rash were attributed to NNRTI treatment. Rash was less frequent in the efavirenz qd and nevirapine bid groups and occurred at similar rates in each of these arms. Non-recommended dosing (nevirapine once daily or nevirapine plus efavirenz) was associated with higher levels of rash (38% and 67% respectively, the highest ever reported in a clinical trial) and will not be discussed further in this summary.

Incidence of rash by grade of severity was also similar between the efavirenz qd and nevirapine bid arms: grade I (erythema/mild) EFV (3 cases), NVP (3 cases); grade IIa (diffuse maculopapular rash) EFV (5), NVP (2); grade IIb (urticaria) (EFV (2), NVP (1); grade III (rash and constitutional symptoms such as fever, or Stevens-Johnson syndrome) EFV (4), NVP (3). No cases of grade IV reaction (toxic epidermal necrolysis) were reported. All differences were non-significant. Five patients were hospitalised for rash, all of whom were taking nevirapine (three NVP qd). One death from heart failure occurred in a patient with underlying congenital heart disease hospitalised for rash.

Recurrence of rash when patients were switched to the other NNRTI was more frequent in patients switched from efavirenz to nevirapine than vice versa, although the overall number of recurrences was small (n=17) and largely concentrated in the group of patients switched from nevirapine plus efavirenz (n=10).

Predictors of rash by multivariate analysis apart from treatment with nevirapine qd or nevirapine plus efavirenz were: CD4 cell increase of greater than 53 cells/mm³ by week 4, or ALT elevation of >34U/l or HIV RNA decline of 2. A CD4 cell count above 250 cells/mm³ was also predictive in women.

The authors express surprise at the incidence of grade III rash in patients receiving standard doses of nevirapine or efavirenz in this study, but overall note that the incidence of rash at these doses was no higher in Thai patients than reported in other cohorts and trials.