Highly active antiretroviral therapy normalizes the potential for MIP-1α production in HIV infection

Design: The CC chemokines RANTES, MIP-1 alpha and MIP-1 beta are ligands for CCR5, which has been identified as the principal co-receptor for macrophage tropic strains of HIV-1, This study investigated whether the inducible levels of RANTES, MIP-1 alpha and MIP-1 beta produced by cultured whole blood samples related to different rates of progression of HIV infection and to the introduction of Nelfinavir-based highly active anti-retroviral therapy (HAART). Methods: Study subjects were HIV-positive and categorized as "slow progressors" (n = 8) or as "fast progressors" (n = 7); the latter group were treated with HAART. MIP-1 alpha, MLP-1 beta and RANTES production was determined using commercial ELISA kits. Results: The inducible production of MIP-1 alpha by whole blood cells in culture was significantly depressed in patients starting therapy compared with "slow progressors" and "normal donors". The levels of MIP-1 alpha significantly increased with therapy at 12 weeks compared with pre-HAART levels (P < 0.05) and became comparable to that of "normals" and "slow progressors". Differences in the inducible levels of MIP-1<beta> and RANTES for the separate, subject groups were not significant. Conclusions: The increase in inducible MIP-1 alpha production following HAART might suggest a role for the, chemokines in HIV disease, either for monitoring the outcome of therapy of HIV disease, or as a direct therapeutic intervention. (C) 2000 The British Infection Society.