The study may have important clinical implications, as the successful use of drug resistance testing at low viral loads may help physicians change a failing treatment regimen earlier, before HIV develops high levels of resistance.

"To date, drug resistance tests have only been used after a patient's treatment fails," said study co-author Dr. Steven G. Deeks of the University of California, San Francisco. "These results indicate that a sensitive phenotypic resistance assay, like the one used in this study, may be useful for predicting and avoiding prolonged treatment failure. I look forward to seeing additional studies on this new frontier in resistance testing."

The study, conducted by researchers from the University of California, San Francisco, the Gladstone Institute of Virology, and ViroLogic, Inc., retrospectively examined resistance profiles, using the PhenoSense HIV phenotypic resistance assay, from 16 treatment-experienced subjects undergoing second-line antiretroviral therapy. The scientists were able to measure drug susceptibility in samples from patients with viral loads below 100 copies/ml, and detected new reductions in drug susceptibility at viral loads as low as 260 copies/ml (for commercial purposes, the PhenoSense HIV assay has been validated for samples with viral loads of 500 copies/ml and above).

Researchers were able to detect emerging drug resistance prior to significant viral load increases in six of 10 subjects, and concluded "phenotypic testing has the potential to provide clinical benefit by facilitating earlier change in treatment regimens before the virus develops significant cross-resistance to related drugs."

Early use of these highly sensitive drug resistance tests may help preserve effective treatment options, which are often severely limited by drug resistance. The study suggests that drug resistance testing could become a standard monitoring tool to evaluate risk of treatment failure.

The study also employed genotypic resistance testing, a method that relies on the interpretation of complex mutations to predict resistance. According to the researchers, "genotypic analysis ... was less valuable in predicting the response to salvage therapy than phenotyping."

"In the future, physicians may use resistance tests more frequently, such as whenever virus is detected by a viral load test," commented lead researcher Dr. Neil Parkin, ViroLogic. "Additional studies will provide us with more informed insight into the clinical and economic impact of performing phenotypic resistance testing at detectable low viral loads."

The study also highlighted the utility of the PhenoSense assay in selecting drug regimens that include a non-nucleoside reverse transcriptase inhibitor, whose potency is durable only in combination with other drugs to which the virus is susceptible.

This article was prepared by AIDS Weekly editors from staff and other reports.

AIDS 2000 Dec 22;14(18):2877-87

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