title: Phenotypic analysis of CD8+ T lymphocytes in a cohort of HIV type 1-infected patients treated with saquinavir, ritonavir, and two nucleoside analogs for 1 year, and association with plasma HIV type 1 RNA.
abstract: The phenotype of circulating CD8+ T lymphocytes and its association with plasma HIV-1 RNA were analyzed in 34 HIV-1-infected subjects, who were treated with saquinavir, ritonavir, and two nucleoside analogs (HAART) for 1 year. Four-color flow cytometry was applied to measure the expression of cell surface antigens CD38, HLA-DR, CD45RA, CD28, and CD62L on CD8+ T lymphocytes. The results were compared with data on 35 HIV-1-seronegative subjects, 18 untreated asymptomatic HIV-1-seropositive individuals, and 24 HIV-1-infected subjects receiving reverse transcriptase inhibitors (RTIs). Subjects receiving HAART showed a significantly elevated number and percentage of CD38- and HLA-DR-positive and CD28-negative CD8+ T lymphocytes as well as a lower percentage of naive (CD45RA+62L+) CD8+ T lymphocytes compared with HIV-1-uninfected controls. Even subjects with undetectable plasma HIV-1 RNA showed a persistent elevation of activated CD8+ T lymphocytes. However, fewer activated CD8+ T lymphocytes were observed in subjects receiving HAART than in untreated individuals and subjects administered RTIs. In individuals receiving RTIs, CD8+ cell activation was not significantly reduced compared with untreated subjects. Of all evaluated activation markers, the percentage of CD8+ T lymphocytes expressing CD38 and the combination of CD38 and HLA-DR showed the best correlation with plasma HIV-1 RNA. The persistence of CD8+ T lymphocyte activation in subjects receiving HAART strongly suggests ongoing viral activity, even in subjects with undetectable plasma HIV-1 RNA. A complete normalization of immunologic changes of CD8+ T lymphocytes would therefore require a more potent drug regimen or a longer duration of therapy.
authors.affiliation: Centre for Immunology, St. Vincent's Hospital, Darlinghurst, NSW, Australia. g.kaufmann@arnie.cfi.unsw.edu.au
authors.forename: G R
authors.initials: GR
authors.lastname: Kaufmann
authors.forename: J J
authors.initials: JJ
authors.lastname: Zaunders
authors.forename: P
authors.initials: P
authors.lastname: Cunningham
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry*; D002469:Cell Separation; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D019041:L-Selectin / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D010641:Phenotype; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; 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; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D019041:L-Selectin; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D019258:Saquinavir; D019438:Ritonavir