Yale University researchers say that they have identified the rare and previously undetectable drug-resistant forms of human immunodeficiency virus (HIV).
Dr. Michael Kozal, Associate Professor at the Yale School of Medicine, says that an innovative genome sequencing technology that quickly detects rare viral mutations was used during the study.
"We found that the fraction of HIV patients that harboured resistance mutations is at least twice as high as previously thought," said Dr. 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," he added.
Dr. Kozal said that the study aimed at determining whether patients who failed therapy early were initially infected with drug resistant HIV strains.
Presented at the 16th International HIV Drug Resistance Workshop in Barbados, the study used samples from 258 subjects of the FIRST study, a large multi-center five-year U.S. trial comparing three different approaches to antiretroviral therapy.
It evaluated the long-term clinical and virologic effects of three initial antiretroviral drug regimens for treatment-naïve HIV infected persons.
The researchers used the Genome Sequencer™ system and Ultra Deep Sequencing technology, 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, a member of the Roche group.
"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," he added.
According to Dr. Kozal, the current genotypic resistance technology available to clinicians may miss many low-level resistant HIV strains that can grow rapidly under drug selection pressure and lead to therapy failure, as it is limited to detecting resistance mutations that are present at levels of approximately 20 per cent or greater in the circulating viral population in a patient.
"This study clearly shows that resistance HIV strains present at the one percent level can lead to premature failure of therapy. It is our hope that in the future, clinicians can use this knowledge to better choose antiretroviral drug combinations that have the ability to suppress these resistant HIV strains, leading to better clinical responses in patients," he said.