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Immonological and Virological Efficacy of Long-Term IL-2 Therapy in HIV-Infected Patients M. L. GOUGEON1, C. ROUZIOUX2, I. LIBERMAN1, M. BURGARD2, J. P. VIARD2, C. CAPITANT2, J. F. DELFRAISSY2, and Y. LEVY*2.
1Inst. Pasteur; 2ANRS, Paris, France Objectives: We evaluated the efficacy of IL-2 in the long term follow up of 27 patients initially randomized in a study comparing binucleosides combined with SC (3MU/m2 bid) or CIV IL-2 (12MU/d) for 5 days, q8weeks, in patients with 250–550 CD4/mm3 and ART naive. In the open phase of the study patients received SC IL-2 as needed to maintain CD4 T cell counts at the plateau.
Methods: We evaluated 1) HIV-specific T cell responses using proliferative and antigen-induced intracellular cytokine assays, and 2) levels of PBMC associated HIV RNA and kinetics of viral DNA and reservoir of latently infected cells.
Results: The median follow up was 41mo (range: 28–49). No AIDS-defining events occurred. ART bitherapy was maintained, except in 4/27 cases who received PI. Mean (range) CD4 cell count/mm3 was 428 (280–531) at entry and 1016 (573–1836) at last assessment (LA). Patients received a median of 2 IL-2 cycles in the open phase. All patients but one had detectable plasma HIV RNA at entry of the randomized phase (mean: 53,500 cp/ml; range: 50–250,850). At LA 10/27 had <20 cp/ml (mean: 1135 cp/ml; range: 20–8100). A continuing decrease of proviral DNA was observed in all patients during the follow up. The median HIV RNA in PBMC was 70 cp/106 PBMC and was undetectable in 4 cases treated with binucleosides. In two of these cases no detectable HIV replication was found after in vitro stimulation of CD8 T cell depleted PBMC. At LA, HIV-specific CD4 T cell responses were noted in 10/27 by either a proliferative assay (mean stimulation index: 4; range: 3.2–6.5) and/or quantification of cytokine synthesis gag-specific CD4+CD69+ cells (median: 0.43%; range: 0.27–9.25%).
Conclusion: Patients treated with IL-2 maintained a high CD4 T cell count in the long term and showed restoration of HIV specific memory T cells with a dramatic reduction of the number of infected cells, albeit treated with binucleosides.
Key Words: HIV Reservoir, IL-2, Immune Restauration
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