July 11, 2002
Switching antiretroviral therapy has become a popular option when metabolic toxicities appear (particularly if the antiretroviral history of the patient allows him or her to do that safely). This is the largest and the best switch study ever done, and I suspect the best that will ever be done. The only problem is that most of the data is already known because this study has been presented previously. I commented on the results of the main trial during the retrovirus conferences of 2002 and 2001 when Jose Maria Gatell presented the virologic and the early metabolic part of it. Meetings should put a limit on the number of repeated presentations, only three months apart, and statisticians should stress the impact these multiple looks at the data has on the strength of the conclusions.
In the parent study, 460 patients were randomized to switch from a successful protease-inhibitor containing regimen to three different arms: nevirapine (155), efavirenz (156) and abacavir (149). All of the patients maintained the nucleoside regimen they were taking before enrolling in the study. All of them had undetectable viral loads (less than 200 HIV RNA copies/mm3) and approximately 50 percent had previous experience with NRTIs before starting their first potent antiretroviral regimen (this becomes important later on).
After one year of followup approximately 77 percent of patients have maintained the original regimen they switched to.
This is a substudy of 92 patients of the original study, approximately 30 per treatment arm. The bottom line -- from the metabolic perspective -- was that patients who switched to nevirapine and efavirenz tended to decrease their triglycerides and increase their HDL cholesterol more than the abacavir arm. Patients who switched to abacavir tended to improve total cholesterol, slightly, but not significantly more than the NNRTI arms.
A very small sub-study of 14 patients looked at changes in body fat distribution after the switch using DEXA and they observed a continuous fat loss, more in the legs than in the arms, but the small numbers seriously limited any strong conclusion. Subjective measurements and personal report showed some improvements, but we all know that quantification of that is quite iffy.
These results (and many other previous studies) seem to suggest that body fat redistribution might be more linked to components of a combination regimen other than PIs, a hypothesis that has been circulating for quite some time.
During the last retrovirus meeting, several groups reported on the effects of switching thymidine analogs, mainly d4T for abacavir, with clear, but modest improvements in the fat atrophy of these patients. This is the only intervention so far that has been able to show an impact on this problem.
In the future we might see some more "switch" studies using triple once-a-day nucleoside regimens, but I think the whole era of large switch studies from PI-based regimens is over.
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