Ziagen (abacavir)

An estimated 3%-8% of patients who take the antiretroviral drug abacavir (Ziagen; also in the fixed-dose combination pills Epzicom and Trizivir) may develop a potentially severe allergic hypersensitivity reaction characterized by a variety of symptoms -- including skin rash, fever, gastrointestinal, and respiratory symptoms - usually within the first 6 weeks after starting the drug.

Individuals who experience such a reaction should not take abacavir again, since doing so can be life-threatening. Because of this risk, physicians typically recommended that patients stop taking abacavir if they have a suspected reaction, although this may lead some people to halt the drug unnecessarily, since these symptoms may be due to causes other than true hypersensitivity.

In recent years, researchers have confirmed that a specific human genetic variation, known as the HLA-B*5071 allele, is strongly associated with susceptibility to abacavir hypersensitivity. A genetic test for HLA-B*5071 can accurately predict which patients are at risk for hypersensitivity, enabling them to avoid the drug, according to a study published in the February 7, 2008 issue of the New England Journal of Medicine (and previously presented at the 4th International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention last summer in Sydney).

PREDICT-1 was a double-blind, prospective trial that included 1956 HIV patients from 19 countries who had not previously received abacavir. Participants were randomly assigned to either undergo prospective HLA-B*5701 screening and to have these results used to determine whether they should receive abacavir, or else to receive the standard-of-care approach of abacavir use without HLA-B*5701 screening (the control group).

All patients who started abacavir were observed for 6 weeks. Abacavir skin patch testing was used to immunologically confirm a clinical diagnosis of hypersensitivity reaction.

Results

Conclusion

Based on these findings, the authors concluded, "HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir."

"In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir," they continued. "Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug."

Prior studies have shown that the HLA-B*5701 variation is even less common among black HIV patients.

"For the first time, we can apply a simple lab test to better identify appropriate individuals for an important HIV medication, abacavir," lead investigator Simon Mallal, MD, said in a press announcement issued by abacavir manufacturer GlaxoSmithKline (GSK). "This is a welcome breakthrough in HIV care and marks our entry into a new era of personalized medicine."

The latest U.S. HIV treatment guidelines recommend HLA-B*5701 screening for patients considering abacavir.

While use of HLA-B*5701 screening and exclusion of susceptible patients can reduce the risk of abacavir hypersensitivity reactions, the researchers and GSK emphasized that the test should not be regarded as a substitute for "clinical vigilance" in monitoring patients starting the drug.

Royal Perth Hospital and Murdoch University, Perth, Australia; Università degli Studi di Brescia, Italy; Hôpital Saint Louis, Paris, France; AIDS Research Initiative, Darlinghurst, Australia; University Medical Center Ljubljana, Slovenia; HIV Research and Clinical Care Center Munich, Germany; Infectioase Constanta, Bucharest, Romania; Volgograd Regional Center for AIDS, Volgograd, Russia; Hospital Arnau de Vilanova, Valencia, Spain; St. George's Hospital and MediTech Media, London, UK; GlaxoSmithKline (GSK), Greenford, UK; GSK, Research Triangle Park, NC; GSK, Brentford, UK.

02/26/08

Sources

S Mallal, E Phillips, G Carosi, and others (PREDICT-1 Study Team). HLA-B*5701 Screening for Hypersensitivity to Abacavir. New England Journal of Medicine 358(6): 568-579. February 7, 2008.

GlaxoSmithKline. New Study Supports Pharmacogenetic Screening To Reduce The Risk Of Abacavir Hypersensitivity Reaction Among HIV Patients. Press release. February 6, 2008.