title: Long-term nonprogressive infection with human immunodeficiency virus type 1 in a hemophilia cohort.
abstract: Seven long-term nonprogressors (LTNPs) have been identified in a cohort of 128 human immunodeficiency virus (HIV)-1 infected individuals with hemophilia. Studies included quantitation of virus by polymerase chain reaction, characterization of primary virus isolates in vitro, analysis of lymphocyte surface markers, and measurement of virus-specific cytotoxic T lymphocytes (CTLs). Viruses of LTNPs exhibited slow growth in vivo and in vitro. LTNPs had expansion of CD8 T cells with increased expression of HLA-DR. Intermittent HIV-1-specific CTL effector activity was detected in freshly isolated peripheral blood mononuclear cells of most LTNPs. CTL precursor frequencies were higher in LTNPs than in patients with progressive disease. Virus antigen-specific lymphoproliferation was vigorous in some LTNPs. Thus, LTNPs in this cohort have maintained remarkably low virus burdens and vigorous HIV-1-specific cell-mediated immunity over a 15-year period. The presence of expanded, activated CD8 T cells with cytotoxic effector function in the peripheral blood suggests ongoing viral replication.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Thomas.Greenough@umass.umed.edu
authors.forename: T C
authors.initials: TC
authors.lastname: Greenough
authors.forename: D B
authors.initials: DB
authors.lastname: Brettler
authors.forename: F
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: L
authors.initials: L
authors.lastname: Alexander
authors.forename: R C
authors.initials: RC
authors.lastname: Desrosiers
authors.forename: S J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: M
authors.initials: M
authors.lastname: Somasundaran
authors.forename: K
authors.initials: K
authors.lastname: Luzuriaga
authors.forename: J L
authors.initials: JL
authors.lastname: Sullivan
mesh_terms: D018791:CD4 Lymphocyte Count; D018925:Chemokines / Q000235:genetics; D015331:Cohort Studies; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D006467:Hemophilia A / Q000150:complications*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D018925:Chemokines; D019707:Receptors, Chemokine