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

The CC chemokines RANTES, MIP-1alpha and MIP-1beta 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-1alpha and MIP-1beta 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).

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-1alpha, MIP-1beta and RANTES production was determined using commercial ELISA kits.

The inducible production of MIP-1alpha by whole blood cells in culture was significantly depressed in patients starting therapy compared with "slow progressors" and "normal donors". The levels of MIP-1alpha significantly increased with therapy at 12 weeks compared with pre-HAART levels (P= O.05) and became comparable to that of "normals" and "slow progressors". Differences in the inducible levels of MIP-1beta and RANTES for the separate subject groups were not significant.

The increase in inducible MIP-1alpha 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.