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. Specific Aim 3: To
determine which ritonavir-based PI regimens alter insulin secretion.
Protocol 3: The effects of ritonavir-based regimens on insulin secretion 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.
Phase:
N/A
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)