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Switch From Suppressive PI to Abacavir
Combo Not Effective in French Cohort Study
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
Switching from a boosted protease inhibitor (PI) regimen to either efavirenz or nevirapine proved effective in a large case-control comparison within the French Hospital Database on HIV [1]. But switching from a boosted PI to a triple-nucleoside abacavir regimen doubled the risk of virologic failure.
Presented by Dominique Costagliola, the analysis began with 6011 antiretroviral-naive people who started a boosted PI with two or more nucleosides from January 1998 through December 2008. No one could be taking abacavir or a nonnucleoside with their PI. Everyone reached a viral load below 500 copies for at least 6 months while taking the same regimen.
Next the investigators identified 439 people who never endured virologic failure on their PI but switched to two or more nucleosides plus efavirenz, nevirapine, or abacavir. Each of those 439 people got matched to three randomly selected nonswitchers who maintained an undetectable viral load for as long as the switchers on their first PI regimen. The French team also matched controls by gender, age, CD4 count below or above 350 before the PI regimen, viral load below 10,000, 10,000 to 100,000, or above 100,000 before the PI regimen, and date of starting their first regimen.
Follow-up continued until virologic failure, the last follow-up visit, death, or December 31, 2008. Potential confounding factors considered in statistical analysis were HIV transmission risk group; nucleoside backbone and PI in first regimen; AIDS, CD4 count, nucleosides, and period at the switch date (or corresponding date in controls); and time between undetectability and the switch date. Costagliola noted that the investigators planned this design to mimic a randomized trial as closely as possible.
Lopinavir was the most popular first PI, taken by 62%, followed by indinavir, taken by 23%. Two thirds of the study group took zidovudine/lamivudine as their first nucleosides. Switchers and nonswitchers were similar in initial CD4 count (82% under 350) and initial viral load (median 100,000 copies). While 196 switchers swapped their PI for efavirenz, 123 changed to nevirapine and 120 to abacavir. Median CD4 count at the switch measured 413, while median CD4 count was lower in nonswitchers (350) at the corresponding date.
Probability of virologic failure 12 months after the switch date was 3.7% in nonswitchers and 5.7% in switchers. But failure probability rates differed depending upon what drug people switched to--3.9% with efavirenz, 7.2% with nevirapine, and 9.0% with abacavir. A statistical model adjusted for the PI in the first regimen and CD4 and AIDS status at the switch date determined that switching to abacavir doubled the risk of virologic failure in 12 months, whereas switching to efavirenz or nevirapine did not significantly raise or lower the risk of failure:
-- Switch to abacavir: adjusted hazard ratio (AHR): 2.0, 95% confidence interval (CI) 1.1 to 3.8
-- Switch to efavirenz: AHR 0.8, 95% CI 0.4 to 1.7
-- Switch to nevirapine: AHR 1.0, 95% CI 0.4 to 2.1
This is the first cohort study of previously untreated people switching from a boosted PI with an undetectable viral load. Costagliola noted that, despite matching for prognostic factors and statistical adjustment for potential confounding variables, this kind of analysis cannot eliminate all possible confounders. Bearing that limitation in mind, the investigators proposed that abacavir "should not be recommended" as the cornerstone of a nucleoside switch regimen in PI-treated people with an undetectable viral load.
Reference
1. Bommenel T, Meynard JL, Launay O, et al. Virological outcomes in ARV-naive patients switching or not from a first successful boosted-PI regimen to efavirenz, nevirapine or abacavir regimens. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract O215.
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