Atherogenic dyslipidemia in HIV-infected individuals treated with proteaseinhibitors

Background-Administration of protease inhibitors (PIs) to HIV-infected indi viduals has been associated with hyperlipidemia. In this study, we characte rized the lipoprotein profile in subjects receiving ritonavir, indinavir, o r nelfinavir, alone or in combination with saquinavir. Methods and Results-Plasma lipoprotein levels were quantified in 93 HIV-inf ected adults receiving PIs. Comparison was done with pretreatment values an d with 28 nonPI-treated HIV-infected subjects. An elevation in plasma chole sterol levels was observed in all PI-treated groups but was more pronounced for ritonavir (2.0+/-0.3 mmol/L [mean+/-SEM], n=46, versus 0.1+/-0.2 mmol/ L in nonPI treated group, P<0.001) than for indinavir (0.8+/-0.2 mmol/L, n= 26, P=0.03) or nelfinavir (1.2+/-0.2 mmol/L, n=21, P=0.01). Administration of ritonavir. but not indinavir or nelfinavir, was associated with a marked elevation in plasma triglyceride levels (1.83+/-0.46 mmol/L, P=0.002). Pla sma HDL-cholesterol levels remained unchanged. Combination of ritonavir or nelfinavir with saquinavir did not further elevate plasma lipid levels. A 4 8% increase in plasma levels of lipoprotein(a) was detected in PI-treated s ubjects with pretreatment Lp(a) values >20 mg/dL. Similar changes in plasma lipid levels were observed in 6 children receiving ritonavir. Conclusions-Administration of PIs to HIV-infected individuals is associated with a marked, compound-specific dyslipidemia. The risk of pancreatitis an d premature atherosclerosis due to Pi-associated dyslipidemia remains to be established.