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

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• 作者：Princy Kumar (1)
  Edwin DeJesus (2)
  Gregory Huhn (3)
  Louis Sloan (4)
  Catherine Butkus Small (5)
  Howard Edelstein (6)
  Franco Felizarta (7)
  Ritche Hao (8)
  Lisa Ross (9)
  Britt Stancil (10)
  Keith Pappa (10)
  Belinda Ha (9)
  
• 关键词：Abacavir ; Cardiovascular biomarker ; Efavirenz ; Fosamprenavir ; HIV ; Lamivudine ; Minority ; Ritonavir ; Underrepresented
• 刊名：BMC Infectious Diseases
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：13
• 期：1
• 全文大小：261KB
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  38. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/269/prepub
  
• 作者单位：Princy Kumar (1)
  Edwin DeJesus (2)
  Gregory Huhn (3)
  Louis Sloan (4)
  Catherine Butkus Small (5)
  Howard Edelstein (6)
  Franco Felizarta (7)
  Ritche Hao (8)
  Lisa Ross (9)
  Britt Stancil (10)
  Keith Pappa (10)
  Belinda Ha (9)
  
  1. Georgetown University Hospital, 3800 Reservoir Rd, NW 5PHC Building, Washington, DC, 20007, USA
  2. Orlando Immunology Center, Orlando, FL, USA
  3. Ruth M Rothstein CORE Center, Chicago, IL, USA
  4. Baylor University Medical Center, Dallas, TX, USA
  5. New York Medical College, Valhalla, NY, USA
  6. Alameda County Medical Center, Oakland, CA, USA
  7. Private Practice, Bakersfield, CA, USA
  8. Chase Brexton Health Services, Inc, Baltimore, MD, USA
  9. ViiV Healthcare, Research Triangle Park, Durham, NC, USA
  10. GlaxoSmithKline, Research Triangle Park, Durham, NC, USA
  

文摘

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-na?ve, 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- 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