November 19, 2002
Various studies have looked at this question before, but few have thus far presented data for over more than one year of follow-up. Results on longer follow-up are important because this is a patient group for which the long term prospects are generally good and the long-term, as well as short-term, consequences of any clinical decision must be evaluated.
Maggiolo et al. presented results from two years of follow-up from a trial which randomized such people to stay on the PI, switch the PI for efavirenz (EFV, Sustiva) or switch the PI for abacavir (ABC, Ziagen). Background NRTIs remained unchanged. At randomization, around one third of the participants were on their first HAART regimen, the median time on antiretrovirals was around four years, with a median time on the current regimen approaching two years.
Key outcomes were virologic failure (consecutive viral load values above 500 copies/mL) or tolerability failure, defined according to WHO grade 4 adverse events or raised lipids (using American Heart Association crieria). Combining these endpoints, the overall proportion with failure at two years was 60 percent in the PI arm and around 30 percent in the switch arms (highly significant difference compared with PI for both switch arms). This result was almost entirely driven by the tolerability component of the endpoint -- virologic failure rates were around 10 percent or less in all three arms by this time. However, these virologic failures are only those which occurred in those still on randomized therapy. It would be important to also compare the viral load status at two years in all patients in each arm, regardless of changes in therapy during the follow-up. In a subgroup analysis, there was a suspicion that abacavir tended to fail more frequently in those with pre-HAART dual NRTI therapy. Another point to note -- with low overall failure rates, around 70 patients per arm is not sufficient to detect a difference in virologic failure rates, so the fact that there was no significant difference should not be read as no difference whatsoever.
The adverse events in the PI arm were mainly lipodystrophy, increased lipids and renal colic. There was generally a more beneficial effect on lipid levels in the two switch arms at two years, with abacavir performing the best in this respect. However, it is important to make a distinction between laboratory adverse events and clinically symptomatic events. The former is limited by our understanding of what laboratory markers are associated with future negative clinical outcomes. Many such markers have not yet even been identified.
Average CD4 count increases were around 130/mm3 in all three arms, despite the fact that the baseline averages were already at 600/mm3.
This study alone will not change clinical practice, but it adds to the pool of evidence available to clinicians and patients which they must use when deciding whether to make a pro-active switch away from a PI regimen.
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