title: PD-1 predicts CD4 loss rate in chronic HIV-1 infection better than HIV RNA and CD38 but not in cryopreserved samples.
abstract: The immunopathogenic factor programmed cell death 1 (PD-1) was compared to CD38 and HIV RNA in predicting actual CD4+ T cell loss rate indicative for clinical progression. This cross sectional exploratory study included 50 consecutive, healthy HIV-infected patients off antiretroviral therapy (ART); 43 had the required observation times > 12 months. PD-1 and CD38 were determined on various T cell subsets by FACS analyses in fresh and later in parallel cryopreserved samples. Here more rapid progressors were relatively defined by having CD4 loss rates < median at -45.7/microl/year. PD-1 and CD38 densities in fresh blood were lower (p<0.001) in patients on ART (n=14) and seronegative controls (n=8). CD4 loss rates correlated significantly to current HIV RNA (R=-0.30), CD38 (R=-0.33) and PD-1 densities (R=-0.38) on CD8+ T cells, and best to DeltaCD38, i.e. the difference in CD38 between the PD-1+CD8+ and CD8+ subsets (R=-0.51). PD-1 was highest on the CD27+CD28-CD8+ subset with best correlation to progression (R=-0.54) in rapid progressors. Logistic regression models from HIV RNA, CD38 and PD-1 predicting rapid progression included PD-1 as best independent variable in combination with DeltaCD38 or CD38, supported by similar results from multiple regression analyses. PD-1 did not correlate with any of the other candidate variables. Cryopreservation reduced the CD38+ and PD-1+ fractions but corresponding densities became more suppressed through a non-linear loss most pronounced in CD38hi/PD-1hi cells with loss of predictive power. In conclusion, PD-1 was the best independent predictor for CD4 loss rates in fresh blood compared with CD38 and HIV RNA.
authors.affiliation: Department of Infectious Diseases, Ullevål University Hospital, Oslo, Norway.
authors.forename: Malin
authors.initials: M
authors.lastname: Holm
authors.forename: Frank Olav
authors.initials: FO
authors.lastname: Pettersen
authors.forename: Dag
authors.initials: D
authors.lastname: Kvale
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000097:blood*; D051017:Apoptosis Regulatory Proteins / Q000097:blood*; D015415:Biomarkers; D018106:CD28 Antigens / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D003430:Cross-Sectional Studies; D015925:Cryopreservation; D018450:Disease Progression; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor; D012367:RNA, Viral / Q000097:blood*
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D018106:CD28 Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012367:RNA, Viral