title: Short communication: enhanced CD8+ T cell apoptosis in HIV-infected adolescents with virologic failure on protease inhibitor-based therapy.
abstract: In this study, we investigated the possibility of differential effects of protease inhibitor (PI)-containing (PI(+)) and PI-sparing (PI(-)) antiretroviral therapies (ART) on CD8(+) T cell apoptosis. We retrospectively analyzed both PD-1 expression and CD8(+) T cell apoptosis in a cross-sectional study of HIV-positive adolescents and young adults (mean age = 17.4 years), with perinatally or behaviorally acquired HIV infection. Fifty-one specimens of cryopreserved peripheral blood mononuclear cells (PBMCs) were analyzed using 7-color flow cytometry: 20 from patients receiving PI(+) ART, 14 from PI(-) ART, and 17 from the untreated. The results showed that percentages of PD-1(+) CD8(+) T cells were strongly correlated with plasma viral loads regardless of treatment (p = 0.0001). The percentage of PD-1(+) CD8(+) T cells was also positively associated with percentages of Annexin V(+) CD8(+) T cells (p = 0.04) in the PI(+)-treated group. The fraction of apoptotic (Annexin V(+)) CD8(+) T cells was associated with viral load in the patients receiving ART that contained one or more protease inhibitors (p = 0.029), but not in the PI(-) or untreated groups. In summary, we found a direct correlation between PD-1 expression on CD8(+) T cells and HIV levels that was not affected by types of medications used in the ART of those adolescents, suggesting that virological success is necessary for PD-1 downregulation. CD8(+) T cell apoptosis was linked to high levels of PD-1 expression and HIV viremia. However, there was a higher degree of apoptosis among viremic patients receiving PI therapy, suggesting an immunologically adverse effect of continuing PI(+) therapy after virological failure.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zuo
authors.forename: Joseph
authors.initials: J
authors.lastname: Church
authors.forename: Marvin
authors.initials: M
authors.lastname: Belzer
authors.forename: Christina
authors.initials: C
authors.lastname: Kitchen
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ank
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schmid
authors.forename: Paul
authors.initials: P
authors.lastname: Krogstad
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000473:pathology*; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D061026:Programmed Cell Death 1 Receptor; D012189:Retrospective Studies; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D017320:HIV Protease Inhibitors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor