The results from a longitudinal study of the relative frequency of various types of HIV mutations associated with the use of antiretroviral therapy (ART) were presented today at a meeting of leading AIDS researchers. The study showed that the prevalence of most key mutations associated with antiretroviral resistance have changed significantly from 1999-2002.
Specifically, the results showed that the prevalence of thymidine analog mutations (TAMs) and other key mutations associated with HIV drug resistance has decreased significantly as reported in the LabCorp Database in recent years, while mutations such as K65R and Y115F are on the rise.
"Although further studies are needed to determine the reasons behind these findings, the increased use of three drug regimens, the introduction of new drugs and/or drug combinations and changes in the submission of patient samples for genotyping may all be factors affecting the changing patterns of HIV mutations in this large sample," said Doug Manion, M.D., vice president of Clinical Development, GSK.
"Resistance to antiretroviral therapy is a major factor that limits the effectiveness of drug therapy. As specific drugs increase or decrease in usage, the prevalence of mutations associated with those drugs should also rise or fall, although many other factors may alter the rate of mutant selection," said Manion.
Resistance Data May Help Predict Best Options
In a related study, resistance data were used to evaluate the median phenotype for 30 mutational patterns associated with resistance to NRTIs. Although further study is needed to determine utility in clinical practice, study investigators believe the technique may be useful to minimize the potential for the rapid selection of mutations resistant to multiple NRTIs arising from specific drug combinations, and guide the selection of treatment options after virologic failure.
"For example, patterns involving 65R and/or 74V in conjunction with M184V are associated with resistance to multiple NRTIs, and require substantially fewer mutations than TAM patterns associated with resistance to multiple NRTIs. TAMs individually and in many combinations do not increase phenotypic resistance to the NRTIs as much as some individual NRTI-associated mutations," said Manion.
In the study, a major database was searched for paired genotypes and phenotypes, and 10,478 unique pairs were studied based on clinically determined phenotypic "breakpoints" associated with resistance to the various drugs in the NRTI class.
GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies and an industry leader in HIV research and therapies. The company is engaged in basic research programs designed to investigate new targets to treat HIV.
AT A GLANCE
The prevalence of most key mutations associated with antiretroviral resistance have changed significantly from 1999-2002.
The largest increase was seen in the K65R and Y115F mutations, while thymidine analog mutations (TAMs) and most mutations associated with protease inhibitors have decreased steadily.
Resistance data from mutational patterns associated with specific drug combinations may be useful in predicting potential treatment failure or choosing future treatment options.
Mary Faye Dark, GlaxoSmithKline
Cell phone: 919-946-0190 — 2/10 through 2/14
Beth Schlesinger, Public Communications Inc.
Pager: 800-759-8888, PIN 1050707 — 2/10 through 2/14 Office: 312-558-1770
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