Evaluation of cardiovascular biomarkers in a randomized trial of fosamprenavir/ritonavir vs. efavirenz with abacavir/lamivudine in underrepresented, antiretroviral-naïve, HIV-infected patients (SUPPORT): 96-week results

Princy Kumar, Edwin DeJesus, Gregory Huhn, Louis Sloan, Catherine Butkus Small, Howard Edelstein, Franco Felizarta, Ritche Hao, Lisa Ross, Britt Stancil, Keith Pappa, Belinda Ha, SUPPORT Study Team, Princy Kumar, Edwin DeJesus, Gregory Huhn, Louis Sloan, Catherine Butkus Small, Howard Edelstein, Franco Felizarta, Ritche Hao, Lisa Ross, Britt Stancil, Keith Pappa, Belinda Ha, SUPPORT Study Team

Abstract

Background: Rates of cardiovascular disease are higher among HIV-infected patients as a result of the complex interplay between traditional risk factors, HIV-related inflammatory and immunologic changes, and effects of antiretroviral therapy (ART). This study prospectively evaluated changes in cardiovascular biomarkers in an underrepresented, racially diverse, HIV-1-infected population receiving abacavir/lamivudine as backbone therapy.

Methods: This 96-week, open-label, randomized, multicenter study compared once-daily fosamprenavir/ritonavir 1400/100 mg and efavirenz 600 mg, both with ABC/3TC 600 mg/300 mg, in antiretroviral-naïve, HLA-B*5701-negative adults without major resistance mutations to study drugs. We evaluated changes from baseline to weeks 4, 12, 24, 48, and 96 in interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), d-dimer, plasminogen, and fibrinogen. Biomarker data were log-transformed before analysis, and changes from baseline were described using geometric mean ratios.

Results: This study enrolled 101 patients (51 receiving fosamprenavir/ritonavir; 50 receiving efavirenz): 32% female, 60% African American, and 38% Hispanic/Latino; 66% (67/101) completed 96 weeks on study. At week 96, levels of IL-6, sVCAM-1, d-dimer, fibrinogen, and plasminogen were lower than baseline in both treatment groups, and the decrease was statistically significant for sVCAM-1 (fosamprenavir/ritonavir and efavirenz), d-dimer (fosamprenavir/ritonavir and efavirenz), fibrinogen (efavirenz), and plasminogen (efavirenz). Values of hs-CRP varied over time in both groups, with a significant increase over baseline at Weeks 4 and 24 in the efavirenz group. At week 96, there was no difference between the groups in the percentage of patients with HIV-1 RNA <50 copies/mL (fosamprenavir/ritonavir 63%; efavirenz 66%) by ITT missing-equals-failure analysis. Treatment-related grade 2-4 adverse events were more common with efavirenz (32%) compared with fosamprenavir/ritonavir (20%), and median lipid concentrations increased in both groups over 96 weeks of treatment.

Conclusions: In this study of underrepresented patients, treatment with abacavir/lamivudine combined with either fosamprenavir/ritonavir or efavirenz over 96 weeks, produced stable or declining biomarker levels except for hs-CRP, including significant and favorable decreases in thrombotic activity (reflected by d-dimer) and endothelial activation (reflected by sVCAM-1). Our study adds to the emerging data that some cardiovascular biomarkers are decreased with initiation of ART and control of HIV viremia.

Trial registration: ClinicalTrials.gov identifier NCT00727597.

Figures

Figure 1
Figure 1
Virologic response (% of patients with HIV-1 RNA <50 copies/mL) over 96 weeks. Virologic response by screening HIV-1 RNA.
Figure 2
Figure 2
Median fasting lipid concentrations at baseline and at 96 weeks.
Figure 3
Figure 3
Change from baseline in cardiovascular biomarkers (expressed as geometric mean ratios) over 96 weeks. Inflammatory biomarkers: A = hs-CRP, B = interleukin-6. Endothelial activation biomarker: C = sVCAM-1. Thrombotic biomarkers: D = d-dimer, E = fibrinogen, F = plasminogen.

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