Efficient inhibition by Raltegravir of HIV-1 Infection in Human Primary Macrophages and in CD4+T Lymphocytes and of the cellular Apoptosis HIV-1 correlated

Background: Raltegravir (RAL) is the first integrase inhibitor approved for the treatment of HIV-1 infection. Consistent evidences show an unusually drop of viral load in the first weeks of treatment. The reason is still not clarified, and could be due to the effect on monocytesmacrophages (M/M). Aim of our study is to investigate the anti-HIV-1 activity of RAL in CD4+ T Lymphocytes and in M/M, and evaluate the ability in preventing the HIV-1 related apoptosis. Methods: CD4+ T lymphocytes and M/M were infected with R5- or X4-using HIV-1 strains in presence of RAL and coreceptors inhibitors (AMD and Maraviroc). HIV-1 p24 production was assessed by immunoenzymatic test. Apoptosis of T cells was evaluated by cytometry. Quantification of viral DNA (integrated and extracromosomic forms) was performed on HIV-1 infected CD4+T lymphocytes by Real time PCR. Student T test was used for statistical analysis. Results: The values of EC50 and EC90 for RAL in HIV-1 Bal infected M/M were 0.3 nM and 6.9 nM respectively, comparable to values in PBMC (0.1 and 6.5 nM). At day 6 the HIV-1 p24 Ag gag-production was negative for all the RAL (120 nM) treated samples (p