Levels of soluble endothelial protein C receptor are associated with CD4+ changes in Maraviroc-treated HIV-infected patients.
BACKGROUND
Inflammation is a key feature of HIV infection and is correlated with long-term negative cardiovascular outcomes. Therapy-induced increases in CD4(+) cell counts can control inflammation, as shown by decreases of coagulation and inflammation markers during efficacious therapy. Maraviroc, a CCR5-antagonist, has resulted in larger increases in CD4(+) counts both in naïve and experienced subjects compared to traditional antiretroviral therapy.


OBJECTIVE
To examine if a member of the protein C anticoagulant and anti-inflammatory pathway, and marker of coagulation and inflammation, the soluble endothelial protein C receptor, is modified by infection and therapy-related variables in patients treated with Maraviroc. Endothelial protein C receptor, together with other established markers of inflammation and coagulation (CRP, IL-6, D-dimer and soluble thrombomodulin) was studied in 43 patients on traditional antiretroviral therapy and in 45 on Maraviroc during 48 weeks of follow-up.


RESULTS
Soluble endothelial protein C receptor was the only marker that could discriminate at least partially between patients with a good response to Maraviroc and patients who did not respond with an adequate increase in CD4(+) cell counts (more than 500 cells/µL by week 48).


CONCLUSIONS
Elevated levels of soluble endothelial protein C receptor, a sensitive marker of endothelial damage, indicated a low level of inflammation and coagulation activation in Maraviroc treated patients not picked up by other widely used markers. Persistent elevated levels of this marker at 48 weeks from beginning of treatment with Maraviroc were related to a poor increase in CD4(+) cells.
Division of Immunology Transplant and Infectious Diseases, Department of Infectious and Tropical Diseases, San Raffaele Scientific Institute, Milan, Italy. silvia.nozza@hsr.it
Silvia
S
Nozza
Manuela
M
Pogliaghi
Stefania
S
Chiappetta
Vincenzo
V
Spagnuolo
Gessica
G
Fontana
Cristina
C
Razzari
Giuseppe
G
Tambussi
Elena Maria
EM
Faioni
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D065100:CCR5 Receptor Antagonists / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000008:administration & dosage*; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000276:immunology / Q000293:injuries / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood / Q000276:immunology*; D014230:Triazoles / Q000008:administration & dosage*
D015703:Antigens, CD; D015415:Biomarkers; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D014230:Triazoles; D000077592:Maraviroc