[en] BACKGROUND: Among people living with HIV, elite controllers (ECs) maintain an undetectable viral load, even without receiving anti-HIV therapy. In non-EC patients, this therapy leads to marked improvement, including in immune parameters, but unlike ECs, non-EC patients still require ongoing treatment and experience co-morbidities. In-depth, comprehensive immune analyses comparing EC and treated non-EC patients may reveal subtle, consistent differences. This comparison could clarify whether elevated circulating interferon-alpha (IFNα) promotes widespread immune cell alterations and persists post-therapy, furthering understanding of why non-EC patients continue to need treatment.
METHODS: Levels of IFNα in HIV-infected EC and treated non-EC patients were compared, along with blood immune cell subset distribution and phenotype, and functional capacities in some cases. In addition, we assessed mechanisms potentially associated with IFNα overload.
RESULTS: Treatment of non-EC patients results in restoration of IFNα control, followed by marked improvement in distribution numbers, phenotypic profiles of blood immune cells, and functional capacity. These changes still do not lead to EC status, however, and IFNα can induce these changes in normal immune cell counterparts in vitro. Hypothesizing that persistent alterations could arise from inalterable effects of IFNα at infection onset, we verified an IFNα-related mechanism. The protein induces the HIV coreceptor CCR5, boosting HIV infection and reducing the effects of anti-HIV therapies. EC patients may avoid elevated IFNα following on infection with a lower inoculum of HIV or because of some unidentified genetic factor.
CONCLUSIONS: Early control of IFNα is essential for better prognosis of HIV-infected patients.
Disciplines :
Immunology & infectious disease
Author, co-author :
Le Buanec, Hélène; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010, Paris, France
Schiavon, Valérie; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010, Paris, France
Merandet, Marine; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010, Paris, France
How-Kit, Alexandre; Laboratory for Genomics Foundation Jean Dausset-CEPH, Paris, France
Song, Hongshuo; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA
Bergerat, David ; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010, Paris, France
Bensussan, Armand ; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010, Paris, France
Bouaziz, Jean-David; Université de Paris, INSERM U976, HIPI Unit, Institut de Recherche Saint-Louis, F-75010, Paris, France ; Dermatology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
Burny, Arsène ; Université de Liège - ULiège ; Global Virus Network, Baltimore, MD, 21201, USA
Darcis, Gilles ; Université de Liège - ULiège > Département des sciences cliniques
Sajadi, Mohammad M; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA ; Global Virus Network, Baltimore, MD, 21201, USA ; University of Maryland School of Medicine, Baltimore, MD, 21201, USA
Kottilil, Shyamasundaran; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA ; Global Virus Network, Baltimore, MD, 21201, USA ; University of Maryland School of Medicine, Baltimore, MD, 21201, USA ; Program in Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA
Zagury, Daniel; 21CBIO, Paris, France
Gallo, Robert C ; Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA. rgallo@ihv.umaryland.edu ; University of Maryland School of Medicine, Baltimore, MD, 21201, USA. rgallo@ihv.umaryland.edu
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