Abstract

Interleukin-2 (IL-2) therapy to prevent CD4 T-cell loss and defer HAART in antiretroviral naive HIV-1 infected patients - Interstart ANRS 119 trial

Presented by Jean-Michel Molina, France.

J.-M. Molina¹, Y. Levy², I. Fournier³, T. Bouler³, M. Bentata⁴, G. Beck Wirth⁵, D. Sereni⁶, F. Jeanblanc⁷, F. Simon⁶, J.-P. Aboulker³, The ANRS 119 Study Group

¹University of Paris 7, Denis Diderot, Paris, France, ²Hopital Henri Mondor, Creteil, France, ³INSERM SC10, Villejuif, France, ⁴Hopital Avicenne, Bobigny, France, ⁵Hopital Mulhouse, Mulhouse, France, ⁶Hopital Saint-Louis, Paris, France, ⁷Hopitaux de Lyon, Lyon, France

Background: In HIV-infection, guidelines recommend HAART initiation when CD4 T-cells are <350. Strategies to delay CD4 decline and defer a lifelong treatment are needed.
Methods: In this randomized open-label trial, 130 HIV-infected adults with 500> CD4 >300 were assigned to IL-2 (n=66) or no treatment (n=64). In the IL-2 group, patients received 4 cycles of 4.5 MIU of IL-2 bid for 5 days every 8 weeks during the first year, and up to 2 optional cycles per year thereafter. The primary endpoint assessed at week 96 was defined as a CD4 count <300, initiation of HAART, occurrence of AIDS-defining event, or death. Follow-up was extended to 150 weeks and multivariate analyses were performed to identify baseline predictors of progression.
Results: At baseline, median age was 36 years, CD4: 383 cells, and viral load : 4.36 log10 cp/ml. Through week 96, rates of progression to the primary endpoint were 35 and 59% in the IL-2 and control arm, respectively (P=0.008) and median changes from baseline in CD4 and viral load were +51 and -64 cells (P<0.0001), and +0.02 and +0.04 log10 cp/ml (P= 0.93), in the IL-2 and control arm, respectively. In controls, baseline CD4 count was the only variable significantly (p<0.0001) associated with progression. In the IL-2 arm, progression was associated with viral load (HR=3.7, p=0.0006) and CD4 count (HR=0.99, p=0.01). Among patients with viral load <4.5 log10 cp/ml, the probability of non progression through week 150 was 66 and 10% in the IL-2 and control arm, respectively (P<0.0001), allowing to defer HAART by 92 weeks in the IL-2 arm. Incidence of AIDS or death, and grades 3 to 4 adverse events was similar between arms.
Conclusions: In asymptomatic HIV-infected patients, notably those with low plasma viral load, IL-2 therapy increased CD4 cell counts and allowed to safely defer the initiation of HAART.