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Immunological success is predicted by enfuvirtide but not interleukin-2 therapy in immunodepressed patients

Viard, Jean-Paula; Fagard, Catherineb; Chaix, Marie-Laurea; Rouzioux, Christinea; Bouteloup, Vincentb; Bentata, Michellec; de Verdière, Nathalie Colind; Pahlavan, Golrize; Weiss, Laurencef; Lévy, Yvesg; Chêne, Genevièveb; for the ANRS 123 ETOILE trial group

doi: 10.1097/QAD.0b013e32832cdc26
Clinical Science: Concise Communication

Objectives: To evaluate the efficacy of adding interleukin-2 (IL-2) to an optimized background treatment in HIV-1 patients with advanced failure.

Design: Randomized, open-label, multicentre controlled trial.

Methods: Patients with CD4 T-cell count of less than 200 cells/μl, 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/μl (primary outcome), of patients with a CD4 cell count increase of at least 50 cells/μl 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/μl 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/μl (14 and 18%) or a CD4 cell count increase of at least 50 cells/μl (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/μl 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/μl (P < 0.001). There was no difference in the rate of AIDS events between groups.

Conclusion: IL-2 failed to increase CD4 cell count in immunocompromised patients with multiple therapeutic failures. Enfuvirtide use was highly associated with success.

aAssistance Publique-Hôpitaux de Paris, Hôpital Necker-Necker Enfants Malades, Université Paris-Descartes, EA3620, Paris, France

bINSERM U897, Bordeaux, France

cAssistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Bobigny, France

dAssistance Publique-Hôpitaux de Paris, Hôpital St. Louis, France

eAssistance Publique-Hôpitaux de Paris, Hôpital Bichat, France

fAssistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, France

gAssistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Paris, France.

Received 6 February, 2009

Revised 6 April, 2009

Accepted 14 April, 2009

Correspondence to Jean-Paul Viard, MD, Service des Maladies Infectieuses et Tropicales, Hôpital Necker, 149 rue de Sèvres, 75743 Paris cedex 15, France. Tel: +33 1 44 49 54 27; fax: +33 1 44 49 54 40; e-mail: jean-paul.viard@nck.aphp.fr

© 2009 Lippincott Williams & Wilkins, Inc.