title: HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis.
abstract: The mechanisms of CD4(+) T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4(+) T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4(+) T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34(+) hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly. Our analyses underline a marked impairment of primary immune resources with the failure to maintain adequate lymphocyte counts. Systemic immune activation emerges as a major correlate of altered lymphopoiesis, which can be partially reversed with prolonged antiretroviral therapy. Importantly, HIV disease progression despite elite control of HIV replication or virologic success on antiretroviral treatment is associated with persistent damage to the lymphopoietic system or exhaustion of lymphopoiesis. These findings highlight the importance of primary hematopoietic resources in HIV pathogenesis and the response to antiretroviral treatments.
authors: Inserm UMR S 945, Infections and Immunity, Avenir Group, Universitě Pierre et Marie Curie-Paris 6, Hôpital Pitiě-Salpêtrière, Paris, France.
authors: Delphine
authors: D
authors: Sauce
authors: Martin
authors: M
authors: Larsen
authors: Solène
authors: S
authors: Fastenackels
authors: Michèle
authors: M
authors: Pauchard
authors: Hocine
authors: H
authors: Ait-Mohand
authors: Luminita
authors: L
authors: Schneider
authors: Amélie
authors: A
authors: Guihot
authors: Faroudy
authors: F
authors: Boufassa
authors: John
authors: J
authors: Zaunders
authors: Malika
authors: M
authors: Iguertsira
authors: Michelle
authors: M
authors: Bailey
authors: Guy
authors: G
authors: Gorochov
authors: Claudine
authors: C
authors: Duvivier
authors: Guislaine
authors: G
authors: Carcelain
authors: Anthony D
authors: AD
authors: Kelleher
authors: Anne
authors: A
authors: Simon
authors: Laurence
authors: L
authors: Meyer
authors: Dominique
authors: D
authors: Costagliola
authors: Steven G
authors: SG
authors: Deeks
authors: Olivier
authors: O
authors: Lambotte
authors: Brigitte
authors: B
authors: Autran
authors: Peter W
authors: PW
authors: Hunt
authors: Christine
authors: C
authors: Katlama
authors: Victor
authors: V
authors: Appay
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D002469:Cell Separation; D018450:Disease Progression; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D038041:Lymphopoiesis / Q000276:immunology*; D008875:Middle Aged; D014779:Virus Replication / Q000276:immunology*