Genetic Screening Recommended Before Abacavir HIV Therapy

Yael Waknine


July 25, 2008

July 25, 2008 — Patients who carry the human leukocyte antigen allele B*5701 (HLA-B*5701) are at higher risk for experiencing potentially fatal hypersensitivity reactions (HSRs) to abacavir sulfate (Ziagen, GlaxoSmithKline), the US Food and Drug Administration (FDA) advised healthcare professionals yesterday.

Screening for the allele is recommended before starting or restarting treatment with abacavir and abacavir-containing products, according to an alert issued by MedWatch, the FDA's safety information and adverse event reporting program. These include abacavir in combination with lamivudine (Epzicom, GlaxoSmithKline) and lamivudine/zidovudine (Trizivir, GlaxoSmithKline).

For those who test positive for HLA-B*5701, abacavir should be considered only under exceptional circumstances, when the potential benefit outweighs the risk for having an HSR. This multiorgan syndrome is characterized by 2 or more clinical signs or symptoms including fever, rash, gastrointestinal symptoms, respiratory symptoms, and constitutional symptoms.

Patients who develop an abacavir HSR require immediate and permanent discontinuation of therapy, the FDA emphasized, noting that this also applies to those who are negative for the HLA-B*5701 allele.

The recommendations were based in part on data from a prospective, double-blind study, showing that prescreening for HLA-B*5701 significantly decreased the risk for an abacavir HSR by 60% (3.4% vs 7.8%; P < .0001). Findings suggest that 61% of patients positive for the allele develop an abacavir HSR compared with only 4.5% of those who test negative.

These conclusions were supported by data from a retrospective case-control study that demonstrated a strong association between the HLA-B*5701 allele and clinically suspected abacavir HSR in both black and white patients.

Abacavir with other antiretroviral agents is indicated for the treatment of HIV-1 infection.

Adverse events related to use of abacavir and abacavir-containing products should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.