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Replacing Enfuvirtide With Raltegravir in France
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16th Conference on Retroviruses and Opportunistic Infections,
February 8-11, 2009, Montreal
Mark Mascolini
A switch from enfuvirtide to raltegravir yielded no virologic or CD4 advantage 6 months later, according to results of a randomized trial of 170 heavily pretreated French patients already taking a suppressive enfuvirtide-containing regimen [1]. (from Jules: another way to look at this is that after switching from Fuzeon to raltegravir there was no fall off in the overall viral load suppression, patients maintained suppression, which was high in both arms (89%) and only 1.2% experienced viral failure in each arm, I take it as a positive in these 3-class resistant patients). As the study name (EASIER) suggests, many people probably prefer swallowing a twice-daily raltegravir pill than injecting themselves twice a day with enfuvirtide, if they are confident of sustained viral control. But raltegravir had no safety advantage in these patients, who had been taking enfuvirtide for a median of more than 2 years.
ANRS investigators recruited adults with a history of resistance to the first three antiretroviral classes. Everyone maintained a viral load below 400 copies for at least 3 months while taking an enfuvirtide-containing regimen. No one had tried an integrase inhibitor before entering the trial, and everyone kept the same background regimen after randomization to continued enfuvirtide or to the raltegravir switch.
The trial's primary endpoint was the proportion of people with virologic failure after 24 weeks when defining virologic failure as (1) a confirmed viral load at or above 400 copies, (2) an unconfirmed last available viral load at or above 400 copies, or (3) an antiretroviral change after a single viral load at or above 400 copies.
The investigators randomized 85 people to each arm, and 84 in each arm completed 24 weeks of follow-up. The groups did not differ much in age (median 48.4 years with enfuvirtide and 47.6 years with raltegravir), median CD4 count (374 and 410), lowest-ever CD4 count (56 and 39), percentage with a viral load below 50 copies (75% and 71%), median duration of antiretroviral therapy (13.6 and 13.7 years), median enfuvirtide duration (2.2 and 2.5 years), or background regimens. The long median duration of enfuvirtide treatment indicates that study participants were responding well to and tolerating this injected fusion inhibitor.
In a 24-week intention-to-treat analysis, 1.2% in each study group (1 patient per group) endured virologic failure. In an on-treatment analysis, 1 person taking raltegravir and none taking enfuvirtide had a virologic failure. At the 24-week point, 89% of people in each arm had a viral load under 50 copies. According to study definitions, these results mean switching to raltegravir is not inferior to maintaining enfuvirtide in this type of patient population. CD4 counts did not change much in either treatment arm.
Grade 3 or 4 adverse events rates were higher with raltegravir than with enfuvirtide (19% versus 11%), but that difference fell short of statistical significance (P = 0.12). Similarly, 12% randomized to raltegravir had a grade 3 or 4 lab abnormality, compared with 6% randomized to continue enfuvirtide, also a nonsignificant difference (P = 0.17).
References
1. De Castro N, Braun J, Charreau I, et al. Switch from enfuvirtide to raltegravir in highly treatment-experienced HIV-1-infected patients: a randomized open-label non-inferiority trial, Easier--ANRS 138. 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal. Abstract 572.
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