New Technologies Help with Drug Selection and Patient Improve Outcomes

Bill Valenti M.D. and Tadd Lazarus M.D.

Results from a study known as the Genotypic Antiretroviral Resistance Testing (GART) Study, conducted by the Community Program for Clinical Research on AIDS (CPCRA), have suggested that using genotypic resistance testing, following failure of a protease inhibitor-containing regimen, can improve treatment results of the next treatment regimen.

Patients included in the study had experienced a three-fold or greater rise in HIV-RNA levels for at least sixteen weeks, while taking an antiretroviral therapy regimen including two nucleoside analogs and a protease inhibitor. Participants also had CD4+ counts of 50-500 cells and at least twelve months of prior antiretroviral therapy. When a patient was enrolled, his or her physician selected a regimen based solely on treatment history. Then half of patients had plasma samples assessed for genotypic evidence of resistance, and an expert panel recommended a treatment regimen based on the resistance test. Then the new treatment regimen was started.

After four to eight weeks of treatment, patients who had resistance testing done had about a half-log lower viral load than patients not given the resistance testing. Furthermore, patients given resistance testing were more likely to have plasma viral loads below the limit of detection than patients not given resistance testing.

Genotypic resistance tests are currently available, but the test is not yet approved by the FDA and many insurers do not pay for the tests.

Upcoming additions to the Public Health Service Treatment Guidelines are expected to incorporate recommendations for resistance testing. An observational study of resistance testing in 30,000 patients, to be known as the VIGILANCE study, is currently enrolling patients.

In the meantime, providers and payers should be getting some experience with the technologies of both genotype and phenotype resistance testing.

One can only speculate that when there is more experience with this technology, patients will fully realize further sustained viral load reductions, improved outcomes, and the more cost-effective use of antiretroviral therapies.

Currently, antiretroviral drug selection is a random event because the resistance profile of the virus that infects an individual patient is unknown. The future requires a greater facility with the application of these technologies in antiretroviral-naive patients so that they may be used to select a regimen that will be maximally effective from the start.

Bill Valenti M.D. is Founding Medical Director of Community Health Network, Rochester, New York, and can be reached by e mail at: .
Tadd Lazarus is Executive Medical Director of Numedx. N