7th Conference - Abstract 60

Hypersensitivity Reactions during Therapy with Abacavir: Analysis of 636 Cases for Clinical Presentation and Risk Factors

S. HETHERINGTON*, H. STEEL, O. NADERER, A. CUTRELL, W. POWELL, and R. SYKES. Glaxo Wellcome, Res. Triangle Park, NC, and Greenford, UK

Abacavir (ABC) is a 2’-deoxyguanosine nucleoside analogue approved for the treatment of HIV-1 infection. Most side effects are generally mild, transient, and include nausea, vomiting and malaise. During clinical trials, several patients developed an idiosyncratic reaction of hypersensitivity (HSR) that resolved on discontinuation, but returned with greater severity of symptoms on reintroduction of ABC. We analyzed 636 cases among over 21,000 patients treated with abacavir during clinical trials and an expanded access program (incidence 3%). The median time to onset of HSR was 11 days, with 94% of cases occurring within 6 weeks of initiation of ABC. The most frequent symptoms were fever (80%), rash (70%), gastrointestinal symptoms (50%), and malaise (40%). Half of the patients presented with 3 or 4 symptoms, and an additional 20% with fever and rash. Fever and/or rash were present in 98% of cases. An important clue to the diagnosis was the evolution of the symptoms (over several days) and evidence for multi-organ system involvement. The rash was mild, and did not progress to severe cutaneous syndromes. Gastrointestinal symptoms without either fever or rash are more likely to indicate common adverse events to antiretroviral therapy (ART) and not HSR. There were 61 cases of re-introduction of ABC following a HSR. The resultant reaction developed within hours and was often severe. The incidence and clinical presentation were nearly identical for pediatric subjects who developed HSR. Laboratory abnormalities noted during HSR included lymphopenia, elevated ALT and CPK, and decreased platelets. Preliminary analysis by logistic regression failed to identify demographic risk factors. The clinical presentation of HSR with abacavir is similar to that reported for other drugs and may be explained by the hapten-hypothesis. Physicians and patients should be familiar with HSR and avoid attempts to reintroduce ABC following this reaction.

Key Words: abacavir, drug reaction, hypersensitivity