title: Changes in CCR5 and CXCR4 expression and beta-chemokine production in HIV-1-infected patients treated with highly active antiretroviral therapy.
abstract: The effect of highly active antiretroviral therapy (HAART) on the expression of CCR5 and CXCR4 HIV coreceptors and the production of the beta-chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta has been investigated in 30 HIV-1-infected individuals during 12-36 months of therapy. CCR5 expression was increased in both CD4 + and CD8 + subsets, whereas CXCR4 expression was upregulated only in CD4 + cells. CCR5 levels normalized during 36 months of therapy and positively correlated with the levels of memory, CD95 +, and HLA-DR + T cells. In contrast, the frequency of CXCR4-expressing cells was not significantly modified by HAART, although a downregulation was observed early after starting treatment. CXCR4 levels were significantly associated with the frequencies of naive T cells and negatively correlated with plasma viral load, CD95, and HLA-DR expression. An increased production of both spontaneous and lectin-induced RANTES, MIP-1alpha, and MIP-1beta was found at baseline in HIV-infected individuals. The spontaneous beta-chemokines production was not modified by 12 months of HAART, although a significant reduction was seen during the first months of therapy. A transient decrease of lectin-stimulated RANTES production was also observed, whereas the reduction of lectin-induced MIP-1alpha persisted for up to 12 months of therapy. In contrast, MIP-1beta secreted by phytohemagglutinin antigen-stimulated peripheral blood mononuclear cells progressively increased during HAART. In conclusion, our data indicate a normalization of CCR5 but not CXCR4 expression during suppressive therapy and changes in beta-chemokine production that may play a part in dictating the efficiency of viral infection and consequently the disease course.
authors.affiliation: Department of Clinical Medicine, University of Rome La Sapienza, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.forename: Antonello
authors.initials: A
authors.lastname: Giovannetti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ensoli
authors.forename: Francesca
authors.initials: F
authors.lastname: Mazzetta
authors.forename: Marco
authors.initials: M
authors.lastname: Marziali
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: De Cristofaro
authors.forename: Donatella
authors.initials: D
authors.lastname: Santini-Muratori
authors.forename: Wilma
authors.initials: W
authors.lastname: Leti
authors.forename: Fernando
authors.initials: F
authors.lastname: Aiuti
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D015497:HIV-1; D006801:Humans; D037102:Lectins / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D019718:Receptors, CXCR4 / Q000096:biosynthesis*
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D037102:Lectins; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4