Increased systemic immune activation and inflammatory profile of long-term HIV-infected ART-controlled patients is related to personal factors, but not to markers of HIV infection severity.
OBJECTIVE
The objective of this study was to analyse the respective roles of personal factors and HIV infection markers on the systemic immune activation/inflammatory profile of long-term antiretroviral treatment-controlled patients.


METHODS
A panel of soluble immune activation/inflammatory biomarkers was measured in 352 HIV-infected treatment-controlled patients from the APROCO-COPILOTE cohort, all of whom were started on a PI in 1997-99 and had a final evaluation 11 years later, and in 59 healthy controls.


RESULTS
A total of 81.5% of the patients were male, with the following characteristics: median age 49 years; 620 CD4 cells/mm(3); 756 CD8 cells/mm(3); CD4/CD8 ratio 0.81; BMI 23.0 kg/m(2); waist-to-hip ratio 0.95. Markers of inflammation-high-sensitivity (hs) IL-6 (median and IQR) (1.3 pg/L, 0.7-2.6), hs C-reactive protein (CRP) (2.1 mg/L, 0.9-4.5) and D-dimer (252 ng/mL, 177-374)-were elevated compared with healthy controls (P < 0.001) and strongly related to each other, as were markers of immune activation [soluble (s) CD14 (1356 ng/mL, 1027-1818), β2-microglobulin (2.4 mg/L, 2.0-3.1) and cystatin-C (0.93 mg/L, 0.82-1.1)]. Inflammatory and immune activation markers were also associated with each other. In HIV-infected patients: age was related to D-dimer, β2-microglobulin and cystatin-C levels; being a smoker was related to increased IL-6 and cystatin-C; and BMI and waist-to-hip ratio were related to CRP. Conversely, markers of HIV infection, current CD4 or CD8 values, CD4 nadir, CD4/CD8 ratio, AIDS stage at initiation of PIs, current viral load and duration of ART were not associated with immune activation/inflammation markers.


CONCLUSIONS
In these long-term treatment-controlled HIV-infected patients, all systemic markers of inflammation and immune activation were increased compared with healthy controls. This was related to demographic and behavioural factors, but not to markers of severity of the HIV infection. Intervention to decrease low-grade inflammation must thus prioritize modifiable personal factors.
Sorbonne Universités, UPMC Univ Paris-6, Inserm UMR_S938, ICAN, APHP Hôpital Tenon and Saint-Antoine, 27 rue Chaligny, F-75571 Paris cedex 12, France.
Jean-Philippe
JP
Bastard
Sorbonne Universités, UPMC Univ Paris-6, Inserm UMR_S938, ICAN, APHP Hôpital Tenon and Saint-Antoine, 27 rue Chaligny, F-75571 Paris cedex 12, France.
Soraya
S
Fellahi
IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, Unité de Coordination du Risque Épidémique et Biologique, Assistance Publique-Hôpitaux de Paris, 16 rue Henri Huchard, F-75890 Paris cedex 18, France.
Camille
C
Couffignal
CMIT, F-75018 Paris, France.
François
F
Raffi
University Hospital of Tours, CHRU, F-37044 Tours cedex 9, France.
Guillaume
G
Gras
INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, 146 rue Léo Saignat, F-33076 Bordeaux cedex, France.
Lucile
L
Hardel
Hotel-Dieu Hospital, 1 Parvis Notre-Dame, Place Jean-Paul II, F-75004 Paris, France.
Alain
A
Sobel
IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, Unité de Coordination du Risque Épidémique et Biologique, Assistance Publique-Hôpitaux de Paris, 16 rue Henri Huchard, F-75890 Paris cedex 18, France.
Catherine
C
Leport
Sorbonne Universités, UPMC Univ Paris-6, Inserm UMR_S938, ICAN, APHP Hôpital Tenon and Saint-Antoine, 27 rue Chaligny, F-75571 Paris cedex 12, France.
Laurence
L
Fardet
Sorbonne Universités, UPMC Univ Paris-6, Inserm UMR_S938, ICAN, APHP Hôpital Tenon and Saint-Antoine, 27 rue Chaligny, F-75571 Paris cedex 12, France jacqueline.capeau@inserm.fr.
Jacqueline
J
Capeau
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007206:Individuality; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
D044966:Anti-Retroviral Agents; D015415:Biomarkers
HCV coinfection; ageing; protease inhibitors; smoking