Clinical Newswire, IAS2009, July 19-22, 2009 (Cape Town, South Africa) - Two studies presented at IAS2009 appear to refute previous observations that associate abacavir with a near twofold increase in the risk of acute myocardial infarction (AMI) in HIV-infected patients receiving HAART. A retrospective analysis and an assessment of biomarkers for cardiovascular effects suggest that the risk may be influenced by multiple factors.
Abacavir was licensed in 1998 by the US FDA, and is used globally in conjunction with lamivudine in HAART regimens. An analysis presented by Dr Roger Bedimo of patients in the Veterans Administration's Clinical Case Registry, USA, identified AMI and cerebrovascular accident (CVA) cases between 1994 and 2004 in 19,424 HIV-infected patients. This corresponds to 75,311 patient-years (PY) of follow-up in the HAART era, with a median of 3.88 years FU.
Patients who were on HAART (receiving 3 or more antiretrovirals) containing abacavir had an acute MI rate of 5.92 per 1000 patient-years. This was numerically but not significantly higher than MI rates on HAART with other NRTI (4.18/1000 PY), on non-HAART ART (4.66/1000 PY), and not on ART (2.98/1000 PY). Hazard ratios for abacavir use, adjusted for age, smoking, diabetes and hypertension, were 1.18 (95% CI: 0.92 - 1.50; p = 0.191) for AMI and 1.16 (0.98 - 1.37; p = 0.096) for CVA.
“The AMI risk appears to be lowest for patients not receiving ART,” noted the authors.
The effects of switching to a regimen including abacavir on biomarkers of cardiovascular damage were evaluated by Dr Andrea de Luca, of the Catholic University, Institute of Clinical Infectious Diseases, Rome, and colleagues. Plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), matrix-metallopeptidase-9 (MMP9), myeloperoxidase (MPO), and high sensitivity C-reactive protein (hs-CRP) were measured on blood samples from before, three months after, and 12 months after the switch in ART
Thirty-five patients who switched to abacavir-containing ART compared to a non-abacavir control group of 22 patients switching to a non-abacavir regimen. The abacavir group were found to have elevated MMP9 levels (p=0.011) at 3 and 12 months. Levels of hs-CRP and MPO were also increased relative to controls at 3 months in the abacavir group (p=0.031,0.036, respectively) but no differences were seen at 12 months. These changes are associated with a decreased fibrinolytic capacity and a possible elevation of cardiovascular risk.
“No significant changes in biomarkers were observed over longitudinal measures,” concluded the authors.
These two studies suggest a possible need for further prospective clarification of the relative cardiovascular risk of abacavir in HIV patients. Studies of cardiovascular risk are liable to be confounded by lifestyle and demographic factors such as smoking, and require adjustment accordingly. A short-term elevation in risk may occur as indicated by the observed elevation of biomarkers hs-CRP, MPO and MMP-9. However, no statistically significant increase in MI or CVA risk was found by the large retrospective analysis.
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