Chemical structure of abacavir.
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Abacavir

Abacavir (ABC) is the most powerful nucleoside analog reverse transcriptase inhibitor (NARTI) used to treat HIV and AIDS. It has been well tolerated, its main side effect being hypersensitivity reactions, which can be dangerous. It is available under the trade name Ziagen™ by GlaxoSmithKline and the combination drug Trizivir™. more...

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Abacavir is one of the most deadly NARTIs, due its ability to trigger to hypersensitivity reactions that lead to sudden death in certain individuals. However, a genetic test is now available that, while not perfect, has reasonable accuracy in predicting whether an individual will be hypersensitive. Over 90% of patients can safely take abacavir.

Strains that are resistant to zidovudine (AZT) or lamivudine (3TC) are generally sensitive to abacavir, whereas strains that are resistant to AZT and 3TC are not as sensitive to abacavir.

History

Abacavir was approved by the Food and Drug Administration (FDA) on December 18, 1998 and is thus the fifteenth approved antiretroviral drug in the United States. Its patent will expire in the United States on 2009-12-26.

Mechanism of action

ABC is an analog of guanosine. It is capable of crossing the blood-brain barrier.

Abacavir is given orally and has a high bio-availability of 83%. It is metabolised primarily through alcohol dehydrogenase or gluconyl transferase.

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Abacavir hypersensitivity reaction predicted by genetic test
From AIDS Treatment News, 3/26/04

About 5% of patients have a potentially serious reaction to abacavir (Ziagen), and must discontinue the drug and never use it again. Now researchers in Australia have reported new data showing that testing for certain genes can accurately predict who will have this reaction.

In their cohort of 248 patients, 18 of whom had the reaction, a genetic test for HLA-B*5701 alone would reduced the risk of abacavir hypersensitivity from 8% to 0.4%--but would result in about 1.6% of their patients being inappropriately denied the drug. Adding a second genetic test would reduce these false positive from 1.5% to 0.4%. These figures will vary by racial groups, or by geographic regions within the same race, because of the different genetic inheritance of different populations.

The researchers presented their findings at the Retroviruses conference (February 8-11, 2004 in San Francisco), and published a full report on March 15. They are now using the testing in their clinical practice, to avoid giving abacavir to patients who are likely to react to it. This testing is not in general use, however.

Incidentally, having HLA-B*5701 is probably an advantage overall, because it is associated with slower HIV progression.

For More Information

For an overview of presentations on this subject at the Retroviruses conference, see "Pharmacogenetics Predict Abacavir (Ziagen) Hypersensitivity" by Deborah Mitchell, published March 1, 2004 on the HIV and Hepatitis site: http://www.hivandhepatitis.com/recent/nrtis/030102d.html

Original paper: Martin AM, Nolan D, Gaudieri S and others. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proceedings of the National Academy of Sciences, USA. Published online before print, March 15, 2004. Free abstract, and link to full text, available at: http://www.pnas.org/cgi/content/abstract/0307067101v1

COPYRIGHT 2004 John S. James
COPYRIGHT 2004 Gale Group

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