Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers
Por:
Chereau, F, Madec, Y, Sabina, C, Obel, N, Ruiz-Mateos, E, Chrysos, G, Fidler, S, Lehmann, C, Zangerle, R, Wittkop, L, Reiss, P, Hamouda, O, Perez, VE, Leal, M, Mocroft, A, de Olalla, PG, Ammassari, A, Monforte, AD, Mussini, C, Segura, F, Castagna, A, Cavassini, M, Grabar, S, Morlat, P, De Wit, S, Lambotte, O, Meyer, L
Publicada:
5 abr 2017
Resumen:
Objective
HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control.
Methods
HICs were identified in COHERE on the basis of >= 5 consecutive viral loads (VL) <= 500 copies/mL over >= 1 year whilst ART-naive, with the last VL <= 500 copies/mL measured >= 5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL > 2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models.
Results
We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds.
Discussion
Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs.
Filiaciones:
Chereau, F:
Univ Paris Saclay, Le Kremlin Bicetre, France
Univ Paris Sud, Le Kremlin Bicetre, France
Univ Versailles Saint Quentin en Yvelines, Le Kremlin Bicetre, France
INSERM, CESP, U1018, Le Kremlin Bicetre, France
Madec, Y:
Inst Pasteur, Emerging Dis Epidemiol Unit, Paris, France
Sabina, C:
UCL, Res Dept Infect & Populat Hlth, Royal Free Campus,Rowland Hill St, London, England
Obel, N:
Rigshosp, Dept Infect Dis, Copenhagen, Denmark
Ruiz-Mateos, E:
Univ Seville, Virgen Rocio Univ Hosp CSIC, Inst Biomed Seville, Lab Immunovirol,Clin Unit Infect Dis Microbiol &, Seville, Spain
Chrysos, G:
Tzaneio Gen Hosp Piraeus, Infect Dis Unit, Dept Med, Piraeus, Greece
Fidler, S:
Imperial Coll, London, England
Lehmann, C:
Univ Cologne, Dept Internal Med 1, Cologne, Germany
German Ctr Infect Res DZIF, Partner Site Bonn Cologne, Cologne, Germany
Zangerle, R:
Med Univ Innsbruck, Dept Dermatol & Venereol, Innsbruck, Austria
Wittkop, L:
Univ Bordeaux, ISPED,Serv Informat Med, INSERM,Pole Sante Publ,Ctr INSERM, Bordeaux Populat Hlth,U1219, Bordeaux, France
Reiss, P:
Stichting HIV Monitoring, Amsterdam, Netherlands
Acad Med Ctr, Dept Global Hlth, Amsterdam, Netherlands
Hamouda, O:
Robert Koch Inst, Dept Infect Dis Epidemiol, Berlin, Germany
Perez, VE:
IdISSC Univ Complutense, Hosp Clin San Carlos, Madrid, Spain
Leal, M:
Univ Seville, Virgen Rocio Univ Hosp CSIC, Inst Biomed Seville, Lab Immunovirol,Clin Unit Infect Dis Microbiol &, Seville, Spain
Mocroft, A:
UCL, Res Dept Infect & Populat Hlth, Royal Free Campus,Rowland Hill St, London, England
de Olalla, PG:
Publ Hlth Agcy Barcelona, Epidemiol Serv, Barcelona, Spain
CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain
Ammassari, A:
IRCCS, Ist Nazl Malattie Infett L Spallanzani, Rome, Italy
Monforte, AD:
Univ Hosp, ASST Santi Paolo & Carlo, Dept Hlth Sci, Infect Dis Unit, Milan, Italy
Mussini, C:
Univ Modena & Reggio Emilia, Clin Infect Dis, Modena, Italy
Segura, F:
Parc Tauli Hosp Univ, Infect Dis Serv, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Castagna, A:
San Raffaele Vita Salute Univ, Milan, Italy
Cavassini, M:
Univ Lausanne, Univ Lausanne Hosp, Infect Dis Serv, Lausanne, Switzerland
Grabar, S:
INSERM, Inst Pierre Louis Epidemiol & Sante Publ, UMR S 1136, Paris, France
UPMC Univ Paris 06, Paris, France
Univ Paris 05, Hop Cochin Hotel Dieu Paris, Paris, France
Morlat, P:
Univ Bordeaux, CHU Bordeaux, INSERM, Serv Med Interne & Malad Infectieuses,U1219, Bordeaux, France
De Wit, S:
Univ Libre Bruxelles, St Pierre Univ Hosp, Dept Infect Dis, Brussels, Belgium
Lambotte, O:
Univ Paris Sud, UMR 1184, Le Kremlin Bicetre, France
IDMIT, DSV iMETI, CEA, Fontenay Aux Roses, France
INSERM, Immunol Viral Infect & Autoimmune Dis, U1184, Le Kremlin Bicetre, France
Hop Bicetre, AP HP, Serv Med Interne & Immunol Clin, Le Kremlin Bicetre, France
Meyer, L:
Univ Paris Saclay, Le Kremlin Bicetre, France
Univ Paris Sud, Le Kremlin Bicetre, France
Univ Versailles Saint Quentin en Yvelines, Le Kremlin Bicetre, France
INSERM, CESP, U1018, Le Kremlin Bicetre, France
Gold, Green Published
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