title: Immunologic and Virologic Progression in HIV Controllers: The Role of Viral "Blips" and Immune Activation in the ANRS CO21 CODEX Study.
abstract: Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up.
authors.affiliation: UMR 1184, Immunologie des Maladies Virales et Autoimmunes (IMVA), Université Paris Sud, Le Kremlin Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noel
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lerolle
authors.affiliation: UMR 1184, Immunologie des Maladies Virales et Autoimmunes (IMVA), Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Lécuroux
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France; INSERM U1018, Centre de recherche en Epidémiologie et Santé des Populations, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.affiliation: UMR 1184, Immunologie des Maladies Virales et Autoimmunes (IMVA), Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Venet
authors.affiliation: Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris, France.
authors.forename: Asier
authors.initials: A
authors.lastname: Saez-Cirion
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327, Paris France; Assistance Publique-Hôpitaux de Paris, Service de Virologie, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Avettand-Fenoël
authors.affiliation: Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France; INSERM U1018, Centre de recherche en Epidémiologie et Santé des Populations, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: INSERM U1018, Centre de recherche en Epidémiologie et Santé des Populations, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Faroudy
authors.initials: F
authors.lastname: Boufassa
authors.affiliation: UMR 1184, Immunologie des Maladies Virales et Autoimmunes (IMVA), Université Paris Sud, Le Kremlin Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019562:Viral Load / Q000276:immunology*