Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection.
T cell activation levels, viral load and CD4(+) T cell counts at early stages of HIV-1 infection are predictive of the rate of progression towards AIDS. We evaluated whether the inflammatory profile during primary HIV-1 infection is predictive of the virological and immunological set-points and of disease progression. We quantified 28 plasma proteins during acute and post-acute HIV-1 infection in individuals with known disease progression profiles. Forty-six untreated patients, enrolled during primary HIV-1 infection, were categorized into rapid progressors, progressors and slow progressors according to their spontaneous progression profile over 42 months of follow-up. Already during primary infection, rapid progressors showed a higher number of increased plasma proteins than progressors or slow progressors. The plasma levels of TGF-β1 and IL-18 in primary HIV-1 infection were both positively associated with T cell activation level at set-point (6 months after acute infection) and together able to predict 74% of the T cell activation variation at set-point. Plasma IP-10 was positively and negatively associated with, respectively, T cell activation and CD4(+) T cell counts at set-point and capable to predict 30% of the CD4(+) T cell count variation at set-point. Moreover, plasma IP-10 levels during primary infection were predictive of rapid progression. In primary infection, IP-10 was an even better predictor of rapid disease progression than viremia or CD4(+) T cell levels at this time point. The superior predictive capacity of IP-10 was confirmed in an independent group of 88 HIV-1 infected individuals. Altogether, this study shows that the inflammatory profile in primary HIV-1 infection is associated with T cell activation levels and CD4(+) T cell counts at set-point. Plasma IP-10 levels were of strong predictive value for rapid disease progression. The data suggest IP-10 being an earlier marker of disease progression than CD4(+) T cell counts or viremia levels.
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
Anne-Sophie
AS
Liovat
Marie-Anne
MA
Rey-Cuillé
Camille
C
Lécuroux
Béatrice
B
Jacquelin
Isabelle
I
Girault
Gaël
G
Petitjean
Yasmine
Y
Zitoun
Alain
A
Venet
Françoise
F
Barré-Sinoussi
Pierre
P
Lebon
Laurence
L
Meyer
Martine
M
Sinet
Michaela
M
Müller-Trutwin
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D054357:Chemokine CXCL10 / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000276:immunology; D019562:Viral Load / Q000276:immunology; D055815:Young Adult
D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D018836:Inflammation Mediators; D020382:Interleukin-18; D053773:Transforming Growth Factor beta1