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Ultra deep sequencing identifies HIV drug resistance at early stage

Rare, previously undetectable drug-resistant forms of HIV have been identified by Yale School of Medicine researcher Michael Kozal, M.D., using an innovative genome sequencing technology that quickly detects rare viral mutations.

Kozal, associate professor of medicine at Yale and senior author of the retrospective study that used samples from an earlier clinical trial, presented the findings today at the 16th International HIV Drug Resistance Workshop in Barbados. We found that the fraction of HIV patients that harbored resistance mutations is at least twice as high as previously thought, said Kozal, who also directs the HIV Program at the VA Connecticut Healthcare System. These low frequency resistant viral strains are not detectable by current resistance testing methods used in the clinic.

While HIV treatment has been largely successful, with dramatic increases in survival over the last decade, a significant number of patients develop drug resistance shortly after treatment begins. This study was designed to determine if patients that fail therapy early were initially infected with drug resistant HIV strains.

Kozal and his team examined samples from 258 subjects of the FIRST study, a large multi-center five-year U.S. trial comparing three different approaches to antiretroviral therapy. The study evaluated the long-term clinical and virologic effects of three initial antiretroviral drug regimens for treatment-nave HIV infected persons.

Kozal and colleagues used the Genome Sequencer system and Ultra Deep Sequencing technology, which was developed by 454 Life Sciences, to detect additional low abundant resistant variants and to predict the failure of antiretroviral therapy.

454 Sequencing can instantly generate hundreds of thousands of long clonal sequence reads that accurately enable the sensitive detection of rare mutations, said Michael Egholm, vice president of research and development at 454 Life Sciences,
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Contact: Karen N. Peart
karen.peart@yale.edu
203-432-1326
Yale University
15-Jun-2007


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