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Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author 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, et al.,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal PLOS ONE
Volume (Issue) 12(4)
Page(s) e0173893 - e0173893
Title of proceedings PLOS ONE
DOI 10.1371/journal.pone.0173893

Open Access

URL http://doi.org/10.1371/journal.pone.0173893
Type of Open Access Publisher (Gold Open Access)

Abstract

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
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