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Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer Jul 2013

Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer

Celia A. Schiffer

Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, …


Inflammatory Biomarker Changes And Their Correlation With Framingham Cardiovascular Risk And Lipid Changes In Antiretroviral-Naive Hiv-Infected Patients Treated For 144 Weeks With Abacavir/Lamivudine/Atazanavir With Or Without Ritonavir In Aries., Benjamin Young, Kathleen E Squires, Lisa L Ross, Lizette Santiago, Louis M Sloan, Henry H Zhao, Brian C Wine, Gary E Pakes, David A Margolis, Mark S Shaefer Feb 2013

Inflammatory Biomarker Changes And Their Correlation With Framingham Cardiovascular Risk And Lipid Changes In Antiretroviral-Naive Hiv-Infected Patients Treated For 144 Weeks With Abacavir/Lamivudine/Atazanavir With Or Without Ritonavir In Aries., Benjamin Young, Kathleen E Squires, Lisa L Ross, Lizette Santiago, Louis M Sloan, Henry H Zhao, Brian C Wine, Gary E Pakes, David A Margolis, Mark S Shaefer

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of