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 Infectious Diseases

Belinda Ha^1,10  Keith Pappa³  Britt Stancil³  Lisa Ross^1,10  Ritche Hao⁵  Franco Felizarta¹  Howard Edelstein⁷  Catherine Butkus Small⁶  Louis Sloan²  Gregory Huhn⁹  Edwin DeJesus⁸  Princy Kumar⁴ 

[1] Private Practice, Bakersfield, CA, USA;Baylor University Medical Center, Dallas, TX, USA;GlaxoSmithKline, Research Triangle Park, Durham, NC, USA;Georgetown University Hospital, 3800 Reservoir Rd, NW 5PHC Building, Washington, DC, 20007, USA;Chase Brexton Health Services, Inc, Baltimore, MD, USA;New York Medical College, Valhalla, NY, USA;Alameda County Medical Center, Oakland, CA, USA;Orlando Immunology Center, Orlando, FL, USA;Ruth M Rothstein CORE Center, Chicago, IL, USA;ViiV Healthcare, Research Triangle Park, Durham, NC, USA

关键词: Underrepresented;    Ritonavir;    Minority;    Lamivudine;    HIV;    Fosamprenavir;    Efavirenz;    Cardiovascular biomarker;    Abacavir;   

Others  :  1147846
DOI  :  10.1186/1471-2334-13-269

 received in 2012-12-11, accepted in 2013-05-24,  发布年份 2013

【 摘 要 】

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

【 授权许可】

   
2013 Kumar et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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