HIV Drug Resistance Identified At Early Stage

Main Category: HIV / AIDS
Also Included In: MRSA / Drug Resistance;  Clinical Trials / Drug Trials;  Genetics
Article Date: 20 Jun 2007 - 19:00 PDT

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454 Life Sciences, a member of the Roche group, and a Yale School of Medicine researcher have announced that they have used the company's Genome Sequencer™ system to identify previously undetectable rare drug resistant HIV variants in samples from an earlier performed clinical trial. The work, presented by Michael Kozal, M.D. of the Yale University School of Medicine and the VA CT Health Care System, was a blinded-retrospective analysis of 258 blood samples taken before drug treatment from HIV infected individuals. The results were presented at the XVI International HIV Drug Resistance Workshop in Barbados and showed that the fraction of patients that harbored resistance mutations is at least twice as high as previously thought. Most low level mutations are undetectable by current resistance testing methods that are used in the clinic. The additional low abundant resistant variants detected by Ultra Deep sequencing were found to be extremely important as it enabled the prediction of early antiretroviral treatment failure with strong statistical significance.

"Current genotypic resistance technology available to clinicians is limited to detecting resistance mutations that are present at levels of approximately 20% or greater in the circulating viral population in a patient. Thus, the current technology used in the clinic may miss many low-level resistant HIV strains which can grow rapidly under drug selection pressure and lead to therapy failure. This retrospective study clearly shows that even resistance mutations present at the 1% level lead to premature failure of therapy" explained Michael Kozal, M.D. the senior author on the study. "In the future, hopefully clinicians can use this knowledge to choose better antiretroviral drug combinations that have the ability to suppress these resistant HIV strains which will lead to better clinical responses in patients."

While treatment of HIV has been largely successful, with dramatic increases in survival over the last decade, a significant number of patients develop drug resistance shortly after treatment is initiated. The collaboration between 454 Life Sciences and Yale University aimed to determine if patients that fail therapy early were initially infected with a drug resistant HIV strain or if mutations arose in response to treatment.

This research project examined samples from 258 subjects of the FIRST study, a large multi-center study conducted in the US comparing three different approaches to antiretroviral therapy. The FIRST study, which lasted 5 years, evaluated the long-term clinical and virologic effects of three initial antiretroviral drug regimens for treatment naïve HIV-infected persons. The CPCRA Statistical Center at the University of Minnesota correlated the sequence data with the patient outcomes, to which 454 Life Sciences was blinded.

"454 Sequencing can instantly generate hundreds of thousands of long clonal sequence reads that accurately enable the sensitive detection of rare mutations" explained Egholm Michael, Ph.D. vice president of research and development at 454 Life Sciences. "Ultra Deep Sequencing provides an essential tool for research on viral diseases and their treatments. The ability to use 454 Sequencing to detect rare viral mutations is a crucial research tool to better understand the early stages of HIV drug resistance."

It is estimated that 22 million people have died from AIDS and over 42 million people are living with HIV/AIDS worldwide. In the U.S. alone, 40,000 new infections occur each year.

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Article adapted by Medical News Today from original press release.
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(http://www.informedhorizons.com/resistance2007/geninfo.html)

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Roche's Diagnostics Division offers a uniquely broad product portfolio and supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories world-wide. For further information, please visit our website at http://www.roche.com/.

About 454

454 Life Sciences Corporation develops and commercializes novel instrumentation for high-throughput DNA sequencing. Specific applications include whole-genome sequencing, RNA analysis and ultra-deep sequencing of target genes. The hallmarks of 454 Sequencing™ are its simple, unbiased sample preparation and massively parallel sequencing, which makes large-scale scientific projects feasible and more affordable. 454 Sequencing and the Genome Sequencer 20 System won The Wall Street Journal's top Innovation Award in 2005 and received an R&D 100 Editor's Choice Award as one of the most technologically significant products in 2006. The 454 Sequencing Center offers sequencing services directly to customers on a fee for service basis. Genome Sequencer systems are distributed by Roche Applied Science. 454 Life Sciences is a business unit of Roche Applied Science, a division of Roche Diagnostics. For additional information, please visit http://www.454.com/.

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Benjamin Carmichael

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