Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers. / Chereau, Fanny; Madec, Yoann; Sabin, Caroline; Obel, Niels; Ruiz-Mateos, Ezequiel; Chrysos, Georgios; Fidler, Sarah; Lehmann, Clara; Zangerle, Robert; Wittkop, Linda; Reiss, Peter; Hamouda, Osamah; Estrada Perez, Vicente; Leal, Manuel; Mocroft, Amanda; Garcia De Olalla, Patricia; Ammassari, Adriana; D'Arminio Monforte, Antonella; Mussini, Cristina; Segura, Ferran; Castagna, Antonella; Cavassini, Matthias; Grabar, Sophie; Morlat, Philippe; De Wit, Stéphane; Lambotte, Olivier; Meyer, Laurence; HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCOORD.
I: PloS one, Bind 12, Nr. 4, e0173893, 2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers
AU - Chereau, Fanny
AU - Madec, Yoann
AU - Sabin, Caroline
AU - Obel, Niels
AU - Ruiz-Mateos, Ezequiel
AU - Chrysos, Georgios
AU - Fidler, Sarah
AU - Lehmann, Clara
AU - Zangerle, Robert
AU - Wittkop, Linda
AU - Reiss, Peter
AU - Hamouda, Osamah
AU - Estrada Perez, Vicente
AU - Leal, Manuel
AU - Mocroft, Amanda
AU - Garcia De Olalla, Patricia
AU - Ammassari, Adriana
AU - D'Arminio Monforte, Antonella
AU - Mussini, Cristina
AU - Segura, Ferran
AU - Castagna, Antonella
AU - Cavassini, Matthias
AU - Grabar, Sophie
AU - Morlat, Philippe
AU - De Wit, Stéphane
AU - Lambotte, Olivier
AU - Meyer, Laurence
AU - HIV Controllers Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCOORD
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Adult
KW - Anti-HIV Agents/therapeutic use
KW - Antiretroviral Therapy, Highly Active/methods
KW - CD4 Lymphocyte Count/methods
KW - CD4-Positive T-Lymphocytes/drug effects
KW - CD8-Positive T-Lymphocytes/drug effects
KW - Female
KW - HIV Infections/drug therapy
KW - HIV-1/immunology
KW - Humans
KW - Male
KW - Viral Load/drug effects
KW - Viremia/drug therapy
KW - Virus Replication/immunology
U2 - 10.1371/journal.pone.0173893
DO - 10.1371/journal.pone.0173893
M3 - Journal article
C2 - 28380038
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4
M1 - e0173893
ER -
ID: 195960552