The deleterious influence of tenofovir-based therapies on the progression of atherosclerosis in HIV-infected patients.
We investigated the potential differential effects of antiretroviral therapies on unbalanced chemokine homeostasis and on the progression of atherosclerosis in HIV-infected patients. A two-year prospective study was performed in 67 consecutive HIV-infected patients initiating antiretroviral therapy with abacavir/lamivudine or tenofovir/emtricitabine. Circulating levels of inflammatory biomarkers, progression of subclinical atherosclerosis and expression levels of selected chemokines genes in circulating leukocytes were assessed. Control subjects showed significantly lower plasma concentrations of CRP, tPA, IL-6, and MCP-1 than HIV-infected patients at a baseline. After two years of followup, the observed decreases in plasma inflammatory biomarker levels were only significant for MCP-1, tPA, and IL-6. The decrease in plasma MCP-1 concentration was associated with the progression of atherosclerosis, and this effect was negligible only in patients receiving TDF-based therapy. Multivariate analysis confirmed that treatment with TDF was positively and significantly associated with a higher likelihood of subclinical atherosclerosis progression. However, the expression levels of selected genes in blood cells only showed associations with the viral load and total and HDL-cholesterol levels. Current antiretroviral treatments may partially attenuate the influence of HIV infection on certain inflammatory pathways, though patients receiving TDF therapy must be carefully monitored with respect to the presence and/or progression of atherosclerosis.
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
Gerard
G
Aragonès
Pedro
P
Pardo-Reche
Laura
L
Fernández-Sender
Anna
A
Rull
Raúl
R
Beltrán-Debón
Esther
E
Rodríguez-Gallego
Jordi
J
Camps
Jorge
J
Joven
Carlos
C
Alonso-Villaverde
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced*; D018932:Chemokine CCL2 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D000068698:Tenofovir
D018932:Chemokine CCL2; D015850:Interleukin-6; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine