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PLoS One. 2017 Apr 5;12(4):e0173893. doi: 10.1371/journal.pone.0173893. eCollection 2017.

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

Author information

1
Université Paris-Saclay, and Université Paris-Sud and Université de Versailles Saint-Quentin-en-Yvelines, and CESP, INSERM U1018, Kremlin-Bicêtre, France.
2
Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.
3
Research Department of Infection and Population Health, UCL, Royal Free Campus, Rowland Hill Street, London, United Kingdom.
4
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
5
Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medecine, Institute of Biomedecine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
6
Department of Medicine, Infectious Disease Unit, Tzaneio General Hospital of Piraeus, Piraeus, Greece.
7
Imperial College, London, United Kingdom.
8
Department of Internal Medicine I, University of Cologne and German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.
9
Department of Dermatology and Venereology, Medical University Innsbruck, Innsbruck, Austria.
10
University Bordeaux, ISPED, INSERM U1219-Bordeaux Population Health, INSERM, ISPED, Centre INSERM U1219-Bordeaux Population Health, CHU de Bordeaux, Pole de santé publique, Service d'information médicale, Bordeaux, France.
11
Stichting HIV Monitoring, Amsterdam, the Netherlands, and Department of Global Health, Academic Medical Center, Amsterdam, the Netherlands.
12
Robert Koch Institute, Department for Infectious Disease Epidemiology, Berlin, Germany.
13
Hospital Clinico San Carlos, IdISSC/Universidad Complutense, Madrid, Spain.
14
Epidemiology Service, Public Health Agency of Barcelona, Barcelona and CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
15
Istituto Nazionale Malattie Infettive L. Spallanzani, IRCCS, Roma, Italy.
16
Infectious Diseases Unit, Department of Health Sciences, ASST Santi Paolo e Carlo, University Hospital, Milan, Italy.
17
Clinic of Infectious diseases, University of Modena and Reggio Emilia, Modena, Italy.
18
Infectious Diseases Service, Parc Taulí Hospital Universitario and Universidad Autónoma de Barcelona, Barcelona, Spain.
19
San Raffaele Vita Salute University, Milano, Italy.
20
Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
21
INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, and UPMC Université Paris 06, and Université Paris Descartes, Hôpital Cochin Hôtel-Dieu Paris, Paris, France.
22
Service de médecine interne et maladies infectieuses, CHU de Bordeaux, Université de Bordeaux, Inserm U1219, Bordeaux, France.
23
Department of Infectious Diseases, St Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
24
Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, and CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, and INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France and Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie clinique, Le Kremlin-Bicêtre, France.

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.

PMID:
28380038
PMCID:
PMC5381858
DOI:
10.1371/journal.pone.0173893
[Indexed for MEDLINE]
Free PMC Article

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