 |
|
|
| |
Switch from Enfuvirtide to Raltegravir in Virologically Suppressed Multidrug-Resistant HIV-1 Infected Patients: Final Results of the Randomized ANRS 138 Trial (EASIER).
|
| |
| |
Reported by Jules Levin
5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19-22 July 2009, Cape Town, South Africa
N. DE CASTRO1, J. BRAUN2, I. CHARREAU2, P. DE TRUCHIS3, F. JEANBLANC4, R. VERDON5, L. SLAMA5, J-L MEYNARD6, J-P. ABOULKER2, J-M. MOLINA1 and the ANRS 138 study group 1Saint-Louis Hosp., Paris 7 University, PARIS, 2INSERM SC10, VILLEJUIF, 3R. Poincare Hosp., GARCHES, 4 E. Herriot Hosp., LYON, 5Cote de Nacre Hosp., CAEN, all in France.
AUTHOR CONCLUSION
Switch from enfuvirtide to raltegravir within a virologically suppressive regimen in patients with multidrug-resistant HIV-1-infection, was effective and well tolerated up to 48 weeks.
All patients from the enfuvirtide arm switched to raltegravir at week 24 and no virologic failure occurred in the second part of the trial and CD4 cell counts remained stable as well.
Compared to the first part of the trial (D0 to W24), the prolongation up to 48 weeks did not show an increase of grade 3 or 4 clinical adverse events. Percentage of patients experiencing emerging grade 3 or 4 laboratory toxicities remained also similar, but grade 3 or 4 increase in liver enzymes occurred in a few patients.
INTRODUCTION
Despite virologic and immunological efficacy of Enfuvirtide (ENF) in treatment experienced HIV-1 infected patients, its long-term use is inconvenient.
Almost all patients suffer from painful subcutaneous nodules at injection sites but ENF discontinuation carries a high risk of virologic failure.
The switch from enfuvirtide to raltegravir within a virologically suppressive regimen has demonstrated sustained virologic efficacy in non randomized studies involving a limited number of patients.
Our study was designed to assess whether a switch from enfuvirtide to raltegravir was safe, well tolerated and virologically non-inferior to the maintenance of enfuvirtide, among patients with multidrugresistant
HIV-infection and viral load suppressed under an enfuvirtide-based antiretroviral regimen.
We recently reported the primary end-point of the study at 24 weeks of follow-up. (N. de Castro et al. Clin. Infect. Dis., in press).
We report here the completion of this trial, up to 48 weeks of follow-up.
METHODS
Statistical Analysis : The crude proportions of patients in each arm who reached the primary study endpoint was compared with a non inferiority test
using the Farrington-Manning method. Non inferiority was established if the upper limit of the 95% two-tailed confidence interval (CI) of the difference in
proportions between groups through week 24 (raltegravir arm minus enfuvirtide arm) was 10% or less.
Categorical variables among the arms were compared with Chi-Square or Fisher's exact tests. Differences in continuous variables between arms were
analyzed with non parametric Wilcoxon rank-sum tests (two-sided alpha level of 0.05).
RESULTS
Figure 2 : Proportion of patients with HIV RNA<50 copies/mL
over 48 weeks
Figure 3 : CD4 T-cell count changes over 48 weeks
Primary end point :
Intention-to-treat analysis: The proportion of patients with virologic failure was 1.2% in each arm (one patient per arm).
The difference (raltegravir minus enfuvirtide) was of 0.01% with a 95% CI = [-6.7%; +6.8%] (p<0.002)
On-treatment analysis: The proportion of patients with virologic failure was 1.2% in the raltegravir arm (one patient with a GSS=0) and 0% in the enfuvirtide arm.
The difference (raltegravir minus enfuvirtide) was of 1.22% with a 95% CI = [-5.6%; +8.1%] (p<0.001)
No virologic failure occurred from W24 to W48 in either arm.
|
| |
|
|
|
|
|
