Gene associated with efavirenz and nevirapine rash identified

Investigators have identified a gene that is associated with the development of allergic rashes in patients taking the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz (Sustiva) and nevirapine (Viramune).

In a study published in the February 19^th edition of AIDS, French investigators report a statistically significant association between the presence of the HLA-DRB1*01 gene and rashes in patients treated with the two NNRTIs. There was no association between the appearance of rashes and other potential risk factors such as age, gender, CD4 cell count or viral load.

They hope that the identification of the association between the gene and allergic rashes during NNRTI treatment could lead to the development of diagnostic tests to identify patients at risk of the side-effect.

Both efavirenz and nevirapine are widely used in anti-HIV drugs, often in first-line therapy. They have relatively few side-effects, but both drugs are associated with allergic rashes. About 20 – 35% of patients taking nevirapine develop such reactions, as do a third of patients treated with efavirenz.

There is increasing evidence that allergy to medicines is influenced by genetics. The HLA-B*5701 gene is strongly associated with a hypersensitivity reaction to the nucleoside reverse transcriptase inhibitor abacavir (Ziagen, also in the combination pills, Kivexa and Trizivir). Patients who are considering treatment with abacavir should have a test to screen for the presence of this gene prior to starting treatment with the drug. Furthermore, nevirapine liver-associated side-effects have been linked to the presence of the HLA-DRB*0101 gene and CD4 cell count.

French investigators conducted a small cohort study to see if there was an association with the HLA-DRB1 gene and allergy to efavirenz and nevirapine, manifested in skin rashes. They also wanted to see if factors such as age, gender, CD4 cell count and viral load were important factors in the development of such an allergic reaction.

Their study involved 21 adult, Caucasian, HIV-positive patients, who started anti-HIV therapy between 2002 and 2004 with a combination of drugs that included efavirenz (seven patients) or nevirapine (14 patients).

A total of six patients developed rashes. None of these patients had liver-related side-effects. The investigators compared the characteristics of these six patients with the other 15 individuals.

All 21 patients were tested for the presence of the HLA-DRB1 gene. They found that five of the six patients (85%) with rashes had the HLA-DRB1*01 gene compared to just one of the patients (15%) who did not develop a rash, a statistically significant difference (p = 0.004).

No other factors were associated with the development of a rash.

“The results of our study suggest that the mechanism of nevirapine/efavirenz-related isolated rash is different from the mechanism in cases with hepatic/systemic reactions”, write the investigators. They add, “the isolated rash risk appears to depend on the presence of the predisposing allele HLA-DRB1*01 alone, whereas the risk of hepatic/systemic reactions is associated with an interaction between genetic and immunological factors.”

They call for further examination of this association in larger cohort studies which could lead “to the development of a diagnostic test, and help decrease or eliminate the incidence of nevirapine/efavirenz hypersensitive reactions.”