title: Assessment of human cytomegalovirus specific T cell immunity in human immunodeficiency virus infected patients in different disease stages following HAART and in long-term non-progressors.
abstract: T cell immunity to human cytomegalovirus (HCMV) was assessed in HAART-treated HIV-1 infected patients (9 asymptomatic, CDC group A; and 22 symptomatic, CDC group B), and in eight HIV-1 long term non-progressors. Patients were either prospectively or cross-sectionally examined for CD4(+) T cell counts, HIV RNA load, HCMV leukoDNAemia, HCMV DNA in urine, lymphoproliferative response (LPR) to HCMV and phytohemagglutinin (PHA), and cytokine secretion (IFN-gamma and IL-4) by HCMV-stimulated peripheral blood mononuclear cell (PBMC) cultures. No patient either progressed to clinical AIDS or developed HCMV active infection during the study period. Twenty-nine patients responded to HAART, though 12 patients failed to recover the LPR to HCMV over the study period (three from CDC group A and nine from CDC group B). In contrast to healthy control individuals, most patients displaying positive LPRs LPRs to HCMV had unstable responses. Sustained LPRs to HCMV were significantly associated with high pre-HAART nadir CD4(+) T cell counts. Long-term suppression of HIV viremia correlated with recovery of LPR to HCMV. Sequential PBMC cultures from most patients secreted IFN-gamma (but not IL-4) at normal levels upon HCMV stimulation, irrespective of the pre-HAART nadir CD4(+) T cell counts and CDC group to which patients belonged. Failure to reconstitute IFN-gamma response was associated with very low pre-HAART nadir CD4(+) T cell counts. Control of HCMV infection in the cohort was associated with either recovery or maintenance of IFN-gamma response rather than with reconstitution of LPR to HCMV. A LPR to HCMV was absent in three out of eight long term non-progressors; contrarily, all patients showed preserved IFN-gamma responses.
authors.affiliation: Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Tamarit
authors.forename: Juan
authors.initials: J
authors.lastname: Alberola
authors.forename: Josep Vicent
authors.initials: JV
authors.lastname: Mira
authors.forename: Carlos
authors.initials: C
authors.lastname: Tornero
authors.forename: María José
authors.initials: MJ
authors.lastname: Galindo
authors.forename: David
authors.initials: D
authors.lastname: Navarro
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016207:Cytokines / Q000096:biosynthesis; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines