NYMC Faculty Publications

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

Author Type(s)

Faculty

DOI

10.1186/1471-2334-13-269

Journal Title

BMC Infectious Diseases

First Page

269

Last Page

269

Document Type

Article

Publication Date

6-7-2013

Keywords

Adolescent, Adult, Aged, Alkynes, Anti-HIV Agents, Benzoxazines, Biomarkers, C-Reactive Protein, Carbamates, Cyclopropanes, Dideoxynucleosides, Drug Combinations, Female, Fibrin Fibrinogen Degradation Products, Fibrinogen, Furans, HIV Infections, Humans, Interleukin-6, Lamivudine, Male, Middle Aged, Organophosphates, Plasminogen, Prospective Studies, Ritonavir, Sulfonamides, Vascular Cell Adhesion Molecule-1, Young Adult

Disciplines

Cardiology | Infectious Disease | Medicine and Health Sciences

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/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.

Link to Full Text

Share

COinS