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


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


RESULTS
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.


CONCLUSIONS
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.
Carter
L M
LM
Department of Immunobiology, St.Thomas' Campus of Guy's, King's and St.Thomas' School of Medicine, King's College London, London, SE1 7EH, UK.
Peters
B S
BS
Ellis
B A
BA
Wolstencroft
R A
RA
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008297:Male; D019888:Nelfinavir / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D019562:Viral Load; D014766:Viremia
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D019259:Lamivudine; D018119:Stavudine; D019888:Nelfinavir