July 13, 2000
What is the role of resistance testing in those having viral rebound on their first protease inhibitor-containing regimen? This issue was addressed in this study, the first prospective study evaluating the impact of phenotype testing when compared to the current standard of care -- which is no resistance testing. (It is unclear what the current standard of care is in this circumstance.) In this study, physicians altered the regimen of 218 patients who had a viral load over 2,000 copies on their regimen. Half were randomized to have the regimen choice guided by the results of a phenotype, while the other half had the regimen selected by the clinicians' best judgement. This presentation updated the results from this study, first presented at the retrovirus conference in January/February of this year.
A few conclusions can be made from these data. First, the test results clearly influenced the clinicians' selection of medications. All the clinicians were asked to define what the new regimen would be before getting any test results back (about four weeks). They compared how the regimen choice was changed in the half that did receive the test versus those who did not receive the test result. While about 40% of the regimens were changed in some way in the control arm, nearly 80% of the regimens changed in the phenotype arm, demonstrating that the test was clearly providing some new information that led to a change in drug selection. This change led to a more successful outcome in the phenotype arm, showing an additional viral load decline of just over one half log at week 16. In addition, there was a trend showing a greater percent with a viral load below detection (using a 400 copy cut-off) on the phenotype arm. This difference was statistically significant in an analysis that does not include those who were lost to follow-up during this time, or who stopped the regimen due to side effects.
Overall, this result adds to the growing body of evidence that resistance testing can improve the viral load response to a new regimen when there is rebound on the current one. However, this test does not provide new drugs to choose from, it mainly identifies which drugs are unlikely to work. This helps to explain why two studies done so far in those who have few if any new medications to take have shown little benefit from resistance testing, while three done in patients with new medication options have shown a benefit when resistance testing guides the regimen choice.