title: Nucleoside-free boosted double PI regimen: significant CD4+ T-cell recovery in patients with poor immunologic response despite virologic suppression.
abstract: Antiretroviral therapy in human immunodeficiency virus infection is occasionally associated with poor immunologic responses despite full suppression of viral replication. As some combinations of nucleoside analogues (NA) have been associated with paradoxical depletion of CD4(+) T- cells, we postulated that depleting the antiretroviral regimen of NAs would improve quantitative immunological parameters. In a longitudinal prospective study we quantified CD4(+) T-cells after removing NAs from antiretroviral therapy. The NA for regimen consisted of atazanavir (300 mg qd), saquinavir (1000 mg bid), and ritonavir (100mg qd) in 14 patients with immunologic failure despite undetectable plasma HIV-RNA (CD4(+) T-cells < 250 cells/microL (<17%) HIV RNA, <= 50 copies/mL). Additionally, we assessed the state of immunologic activation markers (CD38(+)HLA-DR(+) on CD4(+) and CD8(+) T-cells) by flow cytometry. The regimen was well tolerated. During the 48 week study CD4(+) T-cell counts improved significantly (mean and +/- SEM [standard error of mean], baseline: 174/microL (12.4%) [15, 5.8%], week 24: 232/microL (14%) [26, 5.3%], week 48: 267/microL (15.4%) [34, 4.3%]) with preservation of full viral suppression (p<0.05). Activation parameters of CD4(+) T-cells, but not of CD8(+) T-cells, decreased significantly. This treatment strategy may represent an option for patients with poor immunologic responses to antiretroviral therapy despite undetectable viremia.
authors.affiliation: 1st Department of Internal Medicine, University of Cologne, Germany. clara.lehmann@uni-koeln.de
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
authors.forename: Norma
authors.initials: N
authors.lastname: Jung
authors.forename: Anika
authors.initials: A
authors.lastname: Hofmann
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.forename: Christoph
authors.initials: C
authors.lastname: Wyen
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Pia
authors.initials: P
authors.lastname: Hartmann
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D019258:Saquinavir; D019438:Ritonavir