Nevirapine (Viramune) hypersensitivity is much more likely in geographical populations with certain genes, suggests Italian research published in the August edition of the journal AIDS. It showed that 26% of Sardinians were susceptible to the serious side-effect.
Around five per cent of the general population develop severe allergic reactions to the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Symptoms include fever, a severe skin reaction and liver problems, and although most side-effects disappear once the drug is stopped the reaction is fatal in rare cases.
Recent studies have shown that the hypersensitivity reaction occurs in people with a genetic susceptibility. Specifically, researchers believe a set of genes involved in the immune response are involved; the human leukocyte antigen (HLA) system. HLAs are markers that identify cells as "self" and prevent the immune system from attacking them. They are found on all cells of the body and determine white blood cell types. HLA tissue types are used to match donated organs or bone marrow with transplant recipients.
Clinicians at a HIV clinic in Cagliari, Sardinia had noticed that the incidence of nevirapine hypersensitivity was about four times greater than that seen in other populations. Given that the Sardinian population has a very characteristic genetic make-up they decided to look at whether this increase could be linked to specific HLA markers already known to be higher in Sardinians.
Forty-nine Sardinian HIV-infected people treated with nevirapine were studied, of which 13 (26%) had suffered a hypersensitivity reaction (Littera 2006). Researchers then analysed the HLA markers in the 49 people and 82 HIV-infected people who had not been treated with nevirapine. They found that 46% of those who suffered from the reaction had two specific types of HLA markers- termed HLA-Cw8 and HLA-B14- compared to just 5% of those who did not.
They say their research confirms the role of the HLA system in the hypersensitivity reaction and it suggests that HLA-typing of HIV-infected people should make it possible to genetically identify those who are likely to suffer from the reaction. A careful choice of drug therapy in these people could therefore substantially cut the risk of this severe and sometimes life-threatening reaction.
Two months ago another HLA marker - HLA-B*5701 - was shown to be associated with an allergic reaction to the drug abacavir (Ziagen )(Rauch 2006). The study demonstrated that three patients who tested positive for the gene started treatment with abacavir and all three patients developed the hypersensitivity reaction.
Littera R et al. HLA-dependent hypersensitivty to nevirapine in Sardianin HIV patients. AIDS 2006; 20: 1621-1626.
Rauch A et al. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in Western Australian HIV Cohort Study. Clin Infect Dis 43: 99-102, 2006.