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Similar Reductions in Markers of Inflammation and Endothelial Activation after Initiation of
Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC) in the HEAT Study
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Reported by Jules Levin
CROI 209 Feb 8-12 Montreal
Grace A. McComsey1, Kimberly Y. Smith2, Parul Patel3, Nicholaos C. Bellos4, Louis Sloan5, Phillip Lackey6, Princy N. Kumar7, Denise H. Sutherland-Phillips3, Linda Yau3, and Mark S. Shaefer3
1Case School of Medicine, Cleveland, OH, US; 2Rush University Medical Ctr, Chicago, IL, US; 3GSK, RTP, NC, US; 4SW Infectious Disease Associates, Dallas, TX, US; 5North Texas Infectious Disease Consultants, Dallas, TX, US; 6ID Consultants, Charlotte, NC, US; 7Georgetown University, Washington, D.C., US
AUTHOR CONCLUSIONS
ABC/3TC and TDF/FTC containing therapy similarly decreased inflammatory markers associated with CV risk in antiretroviral-naive patients.
Few CV events occurred in HEAT and event rate was similar between arms.
The declines in hsCRP, IL-6, and sVCAM-1 concentrations in the HEAT study do not support the hypothesis of an ABC-induced inflammatory response leading to increased CV risk.
AUTHOR DISCUSSION
Traditional CVD risk factors such as age, male sex, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol, smoking, and diabetes mellitus are common in HIV and are strongly associated with increased CV risk.
Novel biomarkers have been suggested as indicators of increased cardiovascular risk and may provide additional information over and above the use of traditional risk factors in both general and HIV populations.
Comparable declines in circulating sVCAM-1, IL-6, and hsCRP were observed in both groups suggesting a similar decrease in inflammation with both antiretroviral therapies. There were no significant differences between groups for all biomarkers evaluated.
Most subjects had low to average CV risk as measured by hsCRP levels at baseline and the majority had a decrease or no change in hsCRP levels on therapy.
Few CV-related events occurred during study, thus a correlation between inflammatory markers and nucleoside backbone with CV risk was not possible. The net decrease in inflammatory markers observed differs from the SMART study for ABC.
As demonstrated in previous studies, lack of virologic response is significantly correlated with no change or slight increase in sVCAM-1 levels mirroring observations in patients off treatment.
Introduction
Endothelial dysfunction and chronic inflammation have been reported in
HIV-1 infected patients.1
Elevations in the endothelial marker, sVCAM-1, were observed during
treatment interruption in STACCATO2
Elevations in IL-6 and hsCRP were proposed by SMART investigators as
a possible biologic mechanism for the increased risk of cardiovascular
(CV) events among patients treated with ABC in the SMART study3
This analysis compared the effects of initiating ABC/3TC and TDF/FTC on
three inflammatory biomarkers in a prospective, randomized study of ART-naive
patients.
CV Risk and Role of Biomarkers
Cardiovascular disease is the leading cause of death in the general population. Death due to non-AIDS defining illnesses is becoming increasingly more common in HIV-infected patients.1
HIV infection may increase CV risk in part through uncontrolled viral replication leading to dyslipidemia, endothelial dysfunction, and elevation of pro-inflammatory markers.
HIV-infected individuals have a greater prevalence of smoking, insulin resistance and lipid abnormalities compared to those uninfected.
Pro-inflammatory markers have been used as markers for increased CV risk.
References
1. Martinez E, Larrousse M, and Gatell JM. Cardiovascular disease and HIV infection: host, virus or drugs? Curr Opin Infect Dis 2009; 22:28-34.
2. Calmy A, Gayet-Ageron A, Montecucco F, et al. HIV activates markers of cardiovascular risk in a randomized treatment interruption trial: STACCATO. 15th Conference on Retroviruses and Opportunistic infections; February 3-6, 2008, Boston, MA, Abstract 40.
3. Lundgren JD, Neuhaus J, Babiker A et al. for the SMART/INSIGHT; DAD study groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008;22:F17-24.
4. Koenig W, Khuseyinova N. Biomarkers of atherosclerotic plaque instability and rupture. Arterioscler Thromb Vasc Biol 2007;1:15-26.
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