sf, I don't think ICAAC was a "negative twist". It was reality. Here's more info on PI resistance which can happen VERY quickly, even with two PIs (and it has little to do with compliance, as suggested by overly optimistic reseachers):
Rapid Protease Inhibitor Resistance Seen In Advanced HIV Disease
WESTPORT, Oct 15 (Reuters) - In patients with advanced HIV infection treated with
ritonavir and saquinavir, good compliance and optimal plasma drug levels are not
always enough to prevent the emergence of protease mutations, according to members
of the Swiss HIV Cohort.
In the October issue of AIDS, Dr. Bernard Hirschel of the Hopital Cantonal
Universitaire in Geneva and colleagues report the results of a pilot trial of a
combination of the two protease inhibitors administered to 18 patients with a median
CD4 count of 12/microliter and HIV viremia of 5.25 log10 copies/mL. The subjects,
who were protease inhibitor naive, had previously been treated with reverse
transcriptase inhibitors, which were no longer an option.
Following 5 weeks of treatment, 11 patients had responded to the combination
protease regimen. However, by week 13 of treatment, only 6 patients were
categorized as treatment responders, and only 2 of these patients had undetectable
levels of viremia. In general, responders had higher plasma levels of both saquinavir
and ritonavir compared with the non-responders.
Treatment side effects was the major reason that subjects dropped out of the
study--other reasons included patient choice, protocol violation and death.
HIV protease gene sequencing at baseline showed that some of the subjects had
pre-existing protease mutations. "In two compliant non-responders, new mutations
emerged within 5 weeks of combination therapy," the investigators report. "The rapid
appearance of multiple mutations was unexpected and...suggests that data obtained in
moderately advanced HIV disease may not apply to very advance HIV infection."
Overall, Dr. Hirschel's team concluded that "...response to ritonavir plus saquinavir in
advance HIV infection is unpredictable." Only a minority of the subjects in the current
pilot study had suppression of HIV viremia. They found that "[T]he cumulative
emergence of protease mutations conferring resistance to the treatment could not
always be predicted by good compliance and relatively high plasma levels."
AIDS 1997;11:F95-F99.
-Westport Newsroom 203 319 2700 |
