Genetic Variation May Predict Hypersensitivity to Efavirenz (Sustiva) and Nevirapine (Viramune)

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Human Genetic Variation May Predict Hypersensitivity to Efavirenz (Sustiva) and Nevirapine (Viramune)

Recent research has shown that the HLA-B*5701 genetic variation is strongly linked to hypersensitivity reactions to abacavir (Ziagen; also in the fixed-dose combination pills Epzicom and Trizivir), and a screening test for HLA-B*5701 is among the first widespread applications of pharmacogenetics in the field of HIV medicine.

Sustiva (efavirenz)

Viramune (nevirapine)

In a brief report in the February 19, 2008 issue of AIDS, researchers reported on a different genetic variation that appears to be a marker for susceptibility to a type of hypersensitivity reaction in patients taking the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine (Viramune) and efavirenz (Sustiva).

Both drugs may cause skin rash in roughly one-third of patients, though this is often self-limited and clears up with continued use. Nevirapine hypersensitivity may also manifest as liver toxicity; longitudinal data suggest that this is more likely in people with relatively high CD4 counts (above 250 cells/mm3 for women or above 400 cells/mm3 for men).

According to the recent report, HLA typing, demographic characteristics, and immunological risk factors for nevirapine and efavirenz hypersensitivity reactions were studied in a small French cohort of 21 Caucasian HIV patients who started HAART regimens that included efavirenz (n = 7) or nevirapine (n = 14).

Results

• A total of 6 patients developed a skin rash.

• Patients with an isolated rash were significantly more likely to carry the HLA-DRB1*01 allele than those who did not develop a skin rash.

• Almost all individuals who developed a rash after starting the drugs had the genetic variation (5 of 6, or 83%), compared with only 1 person (7%) who did not develop such a reaction.

• No liver toxicity was observed in this study.

• No association was seen between hypersensitivity and factors including sex or CD4 cell count.

Conclusion

"This study suggests that [the] HLA-DRB1*01 allele plays an important role in susceptibility to cutaneous reactions associated with nevirapine and efavirenz in HIV patients," the authors concluded. They also suggested that an isolated NNRTI skin rash may be caused by a different mechanism than more serious liver or systemic reactions.

They expressed hope that further research may lead to the development of a screening test for NNRTI skin reactions like the one now being used to determine susceptibility to abacavir hypersensitivity.

02/26/08

Reference
ZG Vitezica, B Milpied, C Lonjou, and others. HLA-DRB1*01 associated with cutaneous hypersensitivity induced by nevirapine and efavirenz. AIDS 22(4): 540-541. February 19, 2008.