Background:  PI use has been associated with adverse changes in lipoproteins, endothelial dysfunction, and increased cardiovascular disease risk. This study evaluated changes in endothelial function, lipoproteins, and cardiovascular inflammatory markers in hyperlipidemic, atazanavir (ATV) -naive PI-experienced patients who switched their PI to ATV, a PI with a favorable lipid profile.

Methods:  Prospective, randomized, multinational trial in HIV-infected patients on stable non-ATV PI-containing ART with plasma HIV RNA (viral load) <500 copies/mL and fasting low-density lipoprotein (LDL) cholesterol >130 mg/dL or triglycerides (TG) >200 mg/dL. Subjects were randomized (1:1) to continue their current PI regimen or switch their PI to ritonavir-boosted ATV for 24 weeks. Brachial artery flow-mediated dilation was determined by B-mode ultrasound before switching, at 12 and 24 weeks. Lipoproteins were measured by nuclear magnetic resonance spectroscopy and cardiovascular inflammatory proteins were measured by SearchLight assays. Median changes within each arm (signed rank test) and between arms (Wilcoxon test) were calculated.

Results:  We enrolled 50 subjects (median age 43 years, 84% men, 66% white, 42% current smokers, 30% on stable lipid-lowering therapy, 6 years prior ART with 90% on ritonavir-boosted PI [80% on lopinavir/ritonavir]); all completed the study. At baseline: median viral load was <500 copies/mL; CD4 count (cells/mm³) was 510 for ATV and 486 for PI. flow-mediated dilation was 5.0% and 5.3% in the ATV and PI arms, respectively; total cholesterol (TC), LDL, HDL, and TG (mg/dL) were 204, 122, 37, 244 for ATV and 204, 122, 41, 203 for PI arms. At week 12 and 24, flow-mediated dilation did not change in either group. At week 24, TC decreased by 25 (p <0.001) in ATV and 1.5 in the PI arm (ns) (between arms p = 0.009), TG decreased by 58 (p = 0.007) and +3.5 (ns), respectively (between arms p = 0.013). There were no significant between arm differences in total or small LDL, LDL size, total HDL, or HDL size. Significant and within-arm changes were not observed in levels of viral load, CD4 count, glucose, adiponectin, leptin, high-sensitivity C-reactive protein (hs-CRP), intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), tumor necrosis factor receptor-2 (TNFr-2), inositol pyrophosphate (IP-6), interleukin-10 (IL-10), or D-dimer.

Conclusions:   After 24 weeks, significant changes in endothelial function and cardiovascular inflammatory markers were not observed in virologically suppressed hyperlipidemic patients on PI-containing ART who switched their PI to ATV in spite of improved TC and TG. CD4 and viral load remained stable.