title: Sustained suppression of plasma HIV RNA is associated with an increase in the production of mitogen-induced MIP-1alpha and MIP-1beta.
abstract: The chemokine receptor CCR5 has been shown to be a major coreceptor for HIV-1. The chemokines that bind to this receptor (MIP-1alpha, MIP-1beta, and RANTES) are potent inhibitors of HIV replication and may play an important role in the pathophysiology of HIV disease. We investigated the effect of potent antiretroviral therapy (ritonavir and saquinavir) on the production of MIP-1alpha, MIP-1beta, and RANTES in 19 HIV-infected patients who had sustained decreases in plasma HIV RNA levels (<200 copies/ml). Chemokine concentrations were measured in serum, plasma, and PHA-stimulated PBMCs at baseline and 24 and 48 weeks after initiating therapy. MIP-1alpha, MIP-1beta, and RANTES levels in serum and plasma did not significantly change in the 48-week period. In contrast, MIP-1alpha and MIP-1beta secreted by PHA-stimulated PBMCs increased at 24 weeks, with this increase sustained at 48 weeks, whereas no significant change was observed in PHA-induced RANTES production. A significant positive correlation was found between the changes in PHA-induced chemokine production and baseline CD4+ T cell counts. These data demonstrate that sustained suppression of viral replication by potent antiretroviral therapy has a potentially beneficial effect on chemokine production and early initiation of this therapy appears to confer a more favorable chemokine profile.
authors.affiliation: Department of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Kumar
authors.forename: K
authors.initials: K
authors.lastname: Parato
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: E
authors.initials: E
authors.lastname: Sun
authors.forename: D W
authors.initials: DW
authors.lastname: Cameron
authors.forename: J B
authors.initials: JB
authors.lastname: Angel
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008934:Mitogens / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D017320:HIV Protease Inhibitors; D019402:Macrophage Inflammatory Proteins; D008934:Mitogens; D012367:RNA, Viral; D019258:Saquinavir; D019438:Ritonavir