652 Evolution of HIV-1 Proviral DNA per Millions of PBMC in Patients with Advanced HIV Disease (CD4 < 200 cells/mm3) Receiving IL-2 Combined with HAART vs HAART Alone C. Delaugerre*, K. Gourlain, R. Tubiana, G. Carcelain, A. G. Marcelin, C. Chouquet, M. Mouroux, C. Duvivier, B. Autran, D. Costagliola, C. Katlama, V. Calvez Pitié-Salpêtrière Hosp, Paris, France
Background: The ANRS-082 study had confirmed the capacity of IL-2 to increase CD4 lymphocytes in patients (pts) with persistent low CD4 despite HAART. Because this study had included pts with low CD4 and detectable viral load, we wanted to evaluate whether IL-2 could impact HIV-1 proviral DNA load.
Methods: Sixty (60) pretreated pts with CD4 2 00 cells/mm3 and CV < 1000 copies/ml were enrolled in a 6-month (mo) randomized controlled study to evaluate the subcutaneous injection of IL-2 in addition to HAART versus HAART alone. After 24 wks, all pts received IL-2 therapy plus HAART up to week 80. The HIV-1 proviral DNA was quantified at baseline, W24 and W50, by a real-time PCR assay in PBMC. Analysis of resistance mutations was performed at baseline and after 6-months of IL-2.
Results: HIV-1 DNA level in PBMC increased significantly in pts treated with 6 mos of HAART combined to IL-2 (+0,24log10, p = 0,009) compared to an expected slight decrease in patients treated with HAART alone (-0,05log10). Moreover, a DNA increase was observed in pts from control group when receiving 6 mos of IL-2 (+0,34log10). No increase of HIV-1 DNA was seen when this measure was expressed per millions of CD4 cells, probably hidden by the intense increase of CD4 lymphocytes after 6 mos of IL-2 administration. No evolution of resistance mutations in proviral DNA was observed during 6 mos of IL-2 despite the increase of proviral DNA and the occurrence of transient increase of viremia.
Conclusions: Administration of IL-2 combined with HAART in HIV-1 infected pts with severe immunodepression and a slight viral replication led to an increase of HIV-1 proviral DNA per millions of PBMC but without virological failure and emergence of resistance. Two (2) hypothesis, not exclusive, could be proposed in these pts with CD4 count < 200 cells/mm3 receiving IL-2: the direct activation of the replication-competent virus from memory cells and/or the peripheral expansion of pre-existing CD4 cells.
