February 12, 2003
Dr. Margaret Fischl and colleagues presented data on the virologic outcomes for subjects participating in ACTG 388. ACTG 388 was a randomized clinical trial evaluating three different antiretroviral regimens for the treatment of HIV-infected persons with advanced disease (CD4 less than 200 or HIV RNA more than 100,000) and no previous therapy (treatment naive). The treatment arms consisted of:
Treatment failure was defined as:
There were 114 protocol-defined virologic failures. Sixty-four patients elected to continue their initial regimen (19 of those patients switched after at least an additional 16 weeks on their original regimen) and 69 switched to a protocol-defined salvage regimen.
For the continue group there was no difference in virologic outcomes by treatment arm (overall a surprising 59 percent managed to suppress to less than 200 copies). For the continue group, the NR group actually had a higher rate of suppression to less than 200 copies. In the switch group the overall rate of suppression less than 200 copies was 58 percent with no statistical difference according to original treatment assignment. The factors that were associated with a greater likelihood of successful therapy after initial viral failure were the following: relapse as a marker for failure (probably indicating that the patients were capable of a high level of adherence), a lower viral load at virologic failure (making it easier to suppress to less than 200 copies), and a salvage regimen with fewer drugs (probably with higher adherence and fewer side effects and perhaps less resistance on genotyping so it is easier to use an effective simple regimen).
The resistance analysis really didn't contribute much to the analysis. This study used a treatment regimen which was never widely used for good reason (the NFV+IDV arm). This study exposes a major problem with the primary endpoint of the study (namely viral load less than 200 copies/ml at 24 weeks). For persons with advanced disease it often takes more than six months to reach high level suppression. Thus the most likely explanation for the high rate of suppression less than 200 in the continue group is that they met the no response criteria established by the ACTG (never less than 200 copies before week 24) but reached that level of suppression when followed for a longer period of time.
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