Switch from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV-1-infected patients: a randomized open-label trial.
BACKGROUND
Among patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection, salvage regimens including enfuvirtide have demonstrated sustained efficacy. Because of reluctance to use subcutaneous injections, raltegravir may be an alternative to replace enfuvirtide within a suppressive regimen. We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide.


METHODS
A total of 170 patients with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels <400 copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point was the cumulative proportion of patients with virologic failure, defined as a confirmed plasma HIV-1 RNA level >or=400 copies/mL, over 24 weeks. The secondary end points mainly involved safety.


RESULTS
The switch to raltegravir was non-inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2% in both treatment arms in the intention-to-treat analysis (beta = 0.01%; 95% confidence interval, -6.7 to 6.8) and 1.2% and 0%, respectively, in the on-treatment analysis (beta = 1.22%; 95% confidence interval, -5.6 to 8.1). At week 24, 88%-89% of patients in both arms had plasma HIV-1 RNA levels <50 copies/mL. No significant CD4 cell count changes occurred in either arm. Grade 3-4 adverse events and laboratory abnormalities were uncommon and were not different between the treatment arms.


CONCLUSIONS
A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy.


BACKGROUND
NCT00454337
De Castro
Nathalie
N
Department of Infectious Diseases, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital and University of Paris VII Denis Diderot, Paris, France.
Braun
Joséphine
J
Charreau
Isabelle
I
Pialoux
Gilles
G
Cotte
Laurent
L
Katlama
Christine
C
Raffi
François
F
Weiss
Laurence
L
Meynard
Jean-Luc
JL
Yazdanpanah
Yazdan
Y
Delaugerre
Constance
C
Madelaine-Chambrin
Isabelle
I
Aboulker
Jean-Pierre
JP
Molina
Jean-Michel
JM
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011760:Pyrrolidinones; D012367:RNA, Viral; D000077560:Enfuvirtide; D000068898:Raltegravir Potassium