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

J Infect. 2000 Nov;41(3):252-5. doi: 10.1053/jinf.2000.0742.

Abstract

Design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / biosynthesis
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism*
  • HIV-1 / physiology
  • Humans
  • Lamivudine / therapeutic use
  • Lymphocyte Count
  • Lymphocytes / metabolism
  • Macrophage Inflammatory Proteins / biosynthesis*
  • Male
  • Nelfinavir / therapeutic use
  • Stavudine / therapeutic use
  • Viral Load
  • Viremia

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Macrophage Inflammatory Proteins
  • Lamivudine
  • Stavudine
  • Nelfinavir