Coverage of 2007 IAS
(International AIDS Society)

July 2007, Sydney, Australia

New Screening Test May Predict
Life-threatening Side Effect of Ziagen

July 25, 2007

Results presented at the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Sydney show that a simple screening test can be used to predict whether people are at risk for a serious allergic reaction to the anti-HIV drug Ziagen (abacavir). Ziagen is a component of the two fixed-dose combination pills, Epzicom (abacavir + lamivudine) and Trizavir (abacavir + lamivudine + zidovudine).

Results from earlier research as well as clinical practice has shown that between 5–8% of people will have a serious allergy to abacavir. This is called an abacavir hypersensitivity reaction or HSR. Symptoms of abacavir HSR include rash, fever, gastrointestinal upset and malaise. They can range from mild to severe, usually worsen with time and can become serious or fatal, especially if the drug is stopped and restarted.

Previous retrospective studies have shown that people with a genetic variation, called HLA-B5701, were more likely to have this reaction to abacavir. The PREDICT-1 study randomized almost 2,000 people to either take or not take the screening test before starting a HAART regimen with Ziagen. People who tested positive on the screening test were not started on abacavir. Those who tested negative or who didn’t take the screening test started HAART regimens that contained abacavir. Suspected cases of abacavir HSR were confirmed using a skin patch test.

Researchers compared the rates of both suspected and confirmed abacavir HSR in people who took the screening test (who tested negative for HLA-B5701) and people who didn’t get the test. Almost 8% of people who did not take the screening test had suspected abacavir HSR, compared to 3.4% of people who were given the screening test. More importantly, no one given the screening test had a confirmed case of abacavir HSR compared to around 3% of people who didn’t get the test.

It is important to point out that 84% of the people in this study were Caucasian. Research shows that the HLA-B5701 variation is most common among Caucasians. Clinicians have widely reported lower rates of abacavir HSR among people of African and Hispanic origin. Results from a retrospective analysis of HLA testing, called the SHAPE study, found it to be an effective screening tool for people of Asian and Latin ancestry. The sample size of people of African descent was too small to determine the usefulness of HLA testing for this group.

This study has two important implications. First, it shows that HLS screening is very effective at predicting people’s risk of abacavir HSR. Secondly it suggests that abacavir HSR is probably over-diagnosed. Use of HLA testing might allow for greater confidence in using abacavir as part of a HAART regimen. This is particularly important as abacavir is considered by most to be one of the most potent NRTIs, along with Viread (tenofovir), and fear of HSR has been a main reason for many people avoiding its use.