CROI: Abacavir gene testing reveals high levels of hypersensitivity mutation

A small study conducted in Brighton of the efficacy of testing for the HLA-B*5701 mutation that is strongly associated with the hypersensitivity reaction to abacavir (Ziagen) has revealed unexpectedly high levels of the genetic variant in patients of both European and African ethnicity.

However the testing – which started last summer and is ongoing at the city’s Claude Nicol Centre – proved its clinical utility in that there have been no cases of abacavir hypersensitivity recorded since the testing policy was introduced.

The B*5701 test, which is covered in depth in AIDS Treatment Update 152, is the first time a genetic test has been used in HIV medicine to predict which patients will react badly to a drug. The immune-mediated reaction to abacavir, which has caused 31 fatalities globally and results in hospitalisation in 9-20% of cases, has, as the researchers comment, made abacavir “less attractive” as an alternative NRTI drug to tenofovir (Viread) or AZT (zidovudine, Retrovir).

At the time of submitting the abstract to Conference on Retroviruses and Opportunistic Infections in October 2005, the clinic had tested 114 patients, of whom 82% were men. Three-quarters of the patient group were of white ethnicity, 20% black and 4% classed as ‘other’. At that point 14% of the patient group were found to be positive for B*5701, 16% of white and 9% of black patients. This is twice the average rate recorded in Caucasians, and the allele (mutation) had previously been thought to be very uncommon in patients of African background.

By the time of the conference 16 weeks later, another 157 patients had been tested, making 271 in total. The proportion positive to B*5701 has somewhat decreased, but still stood at 10% overall, 13% in whites and 7% in blacks.

The researchers note, however that none of a group of patients attending the clinic of South African Zulu origin had the allele.

Of the patients tested, 95 were new to HIV therapy and 176 were already taking non-abacavir-containing regimens, of whom 121 (69%) were taking AZT. After taking the test, 81 patients negative to B*5701 either started or switched to abacavir-containing regimens and had been taking it for at least six weeks by the time of the conference. No hypersensitivity reactions have been seen in these patients.

Prior to testing, 20 patients out of 322 prescribed abacavir had suffered from the hypersensitivity reaction, a rate of 6%, which accords with other estimates of its frequency. The clinic’s findings may indicate that in this population at least there may be a higher rate than expected of patients who had B*5701 but did not get hypersensitivity.

The researchers comment: “Incorporating this strategy into routine clinical practice is likely to lead to significant changes in therapy.”