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

Fanny Chereau, Yoann Madec, Caroline Sabin, Niels Obel, Ezequiel Ruiz-Mateos, Georgios Chrysos, Sarah Fidler, Clara Lehmann, Robert Zangerle, Linda Wittkop, Peter Reiss, Osamah Hamouda, Vicente Estrada Perez, Manuel Leal, Amanda Mocroft, Patricia Garcia De Olalla, Adriana Ammassari, Antonella D.Arminio Monforte, Cristina Mussini, Ferran SeguraAntonella Castagna, Matthias Cavassini, Sophie Grabar, Philippe Morlat, Stéphane De Wit, Olivier Lambotte, Laurence Meyer, Ali Judd, Giota Touloumi, Josiane Warszawski, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Ferdinand Wit, Maria Prins, Heiner Bucher, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Claire Thorne, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Barbara Bartmeyer, Nikoloz Chkhartishvili, Antoni Noguera-Julian, Andrea Antinori, Norbert Brockmeyer, Luis Prieto, Pablo Rojo Conejo, Antoni Soriano-Arandes, Manuel Battegay, Roger Kouyos, Pat Tookey, Jordi Casabona, Jose M. Miró, Deborah Konopnick, Tessa Goetghebuer, Anders Sönnerborg, Carlo Torti, Ramon Teira, Myriam Garrido, David Haerry, Jose Ma Miró, Dominique Costagliola, Antonella D'Arminio-Monforte, Dorthe Raben, Geneviève Chêne, Diana Barger, Christine Schwimmer, Monique Termote, Maria Campbell, Casper M. Frederiksen, Nina Friis-Møller, Jesper Kjaer, Rikke Salbøl Brandt, Juan Berenguer, Julia Bohlius, Vincent Bouteloup, Alessandro Cozzi-Lepri, Mary Anne Davies, Maria Dorrucci, David Dunn, Matthias Egger, Hansjakob Furrer, Marguerite Guiguet, Valériane Leroy, Sara Lodi, Sophie Matheron, Susana Monge, Fumiyo Nakagawa, Roger Paredes, Andrew Phillips, Massimo Puoti, Eliane Rohner, Michael Schomaker, Colette Smit, Jonathan Sterne, Rodolphe Thiebaut

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    © 2017 Chereau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.
    Original languageEnglish
    Article numbere0173893
    JournalPLoS ONE
    Issue number4
    Publication statusPublished - 1 Apr 2017


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