Immunological success is predicted by enfuvirtide but not interleukin-2 therapy in immunodepressed patients.
OBJECTIVE
To evaluate the efficacy of adding interleukin-2 (IL-2) to an optimized background treatment in HIV-1 patients with advanced failure.


METHODS
Randomized, open-label, multicentre controlled trial.


METHODS
Patients with CD4 T-cell count of less than 200 cells/microl, plasma HIV-1 RNA of more than 10 000 copies/ml and a genotypic sensitivity score showing two or less active drugs were randomized to either eight IL-2 cycles with optimized background treatment or optimized background treatment alone. Optimization was made according to genotypic sensitivity score. Enfuvirtide was added in enfuvirtide-naive patients. Evaluation was performed at week 52 on the proportions of patients with CD4 cell count of at least 200 cells/microl (primary outcome), of patients with a CD4 cell count increase of at least 50 cells/microl from week 0, on plasma HIV-1 RNA and HIV-related events.


RESULTS
Fifty-six patients were analysed. Median age was 43 years, 61% were at Center for Disease Control and Prevention stage C, 43% had a genotypic sensitivity score of 0, median baseline CD4 cell count and plasma HIV-1 RNA values were 64 cells/microl and 4.9 log10 copies/ml, respectively. Treatment could be optimized in 23 patients. At week 52, in the IL-2 and control groups, the proportion of patients with CD4 cell count of at least 200 cells/microl (14 and 18%) or a CD4 cell count increase of at least 50 cells/microl (25 and 32%) and median plasma HIV-1 RNA were not significantly different. In multivariate analysis, optimization with enfuvirtide and baseline CD4 cell count were statistically associated with CD4 cell count of at least 200 cells/microl at week 52 (P = 0.003 and P = 0.01). Optimization with enfuvirtide was the only factor associated with a CD4 cell count gain of at least 50 cells/microl (P < 0.001). There was no difference in the rate of AIDS events between groups.


CONCLUSIONS
IL-2 failed to increase CD4 cell count in immunocompromised patients with multiple therapeutic failures. Enfuvirtide use was highly associated with success.
Viard
Jean-Paul
JP
Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Necker Enfants Malades, Université Paris-Descartes, France. jean-paul.viard@nck.aphp.fr
Fagard
Catherine
C
Chaix
Marie-Laure
ML
Rouzioux
Christine
C
Bouteloup
Vincent
V
Bentata
Michelle
M
de Verdière
Nathalie Colin
NC
Pahlavan
Golriz
G
Weiss
Laurence
L
Lévy
Yves
Y
Chêne
Geneviève
G
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D000077560:Enfuvirtide; D004812:Epidemiologic Methods; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage*; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage*; D012367:RNA, Viral / Q000276:immunology; D017211:Treatment Failure
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D007376:Interleukin-2; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide