HIV Antiretroviral Drugs and Metabolism

Hypothesis 1: Ritonavir-based regimens increase triglycerides and VLDL by both increasing VLDL production and decreasing VLDL clearance. Specific Aim 1A: To quantify the effect of ritonavir on VLDL production and clearance using stable isotope turnover and other clearance methods. Specific Aim 1B: To determine the composition of the triglyceride rich particles. Protocol 1: The effects of ritonavir-based regimens on VLDL production, VLDL clearance and triglyceride-rich lipoprotein composition in healthy normal volunteers. HIV-seronegative volunteers will be studied before and at the end of four weeks of taking ritonavir, lopinavir/ritonavir or atazanavir/ritonavir. Hypothesis 2: NNRTI drugs do not increase HDL by increasing apo AI production, but rather by decreasing apo AI clearance, prolonging time in circulation. Specific Aim 2A: To determine the composition of HDL before and after NNRTI and assess its function. Specific Aim 2B: To quantify the effect of NNRTI on apo AI production and clearance using stable isotopes. Specific Aim 2C: To determine if the NNRTI induced increase in HDL is accompanied by improvement in flow mediated vasodilation and circulating markers of endothelial function Protocol 2A: The effects of efavirenz on HDL composition, HDL function, apo AI production, apo AI clearance, flow mediated vasodilation and circulating markers of endothelial dysfunction in healthy normal volunteers. HIV-seronegative volunteers will be studied before and at the end of six weeks of taking efavirenz. Protocol 2B: The effects of starting an efavirenz-based regimen on HDL composition, HDL function, apo AI production, apo AI clearance, flow mediated vasodilation and circulating markers of endothelial dysfunction in patients with HIV infection. HIV-infected patients whose care providers have prescribed an efavirenz-based regimen will be studied before and after six weeks of starting efavirenz. Hypothesis 3: Ritonavir-based PI regimens impair insulin secretion.