BRANFORD, Conn., June 15, 2007 454 Life Sciences, a member of the Roche group, and a Yale School of Medicine researcher today announced that they have used the companys Genome Sequencer system to identify previously undetectable rare drug resistant HIV variants in samples from an earlier performed clinical trial. The work, presented today 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 today 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.