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

BMC Infect Dis. 2013 Jun 7;13:269. doi: 10.1186/1471-2334-13-269.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Biomarkers
  • Carbamates
  • Cyclopropanes
  • Dideoxynucleosides
  • Drug Combinations
  • Fibrin Fibrinogen Degradation Products
  • Furans
  • Interleukin-6
  • Organophosphates
  • Sulfonamides
  • Vascular Cell Adhesion Molecule-1
  • abacavir, lamivudine drug combination
  • fibrin fragment D
  • Lamivudine
  • Fibrinogen
  • Plasminogen
  • C-Reactive Protein
  • efavirenz
  • Ritonavir
  • fosamprenavir

Associated data

  • ClinicalTrials.gov/NCT00727597