Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV Cohort Study.
BACKGROUND
Administration of protease inhibitors (PIs) to HIV-infected individuals has been associated with hyperlipidemia. In this study, we characterized the lipoprotein profile in subjects receiving ritonavir, indinavir, or nelfinavir, alone or in combination with saquinavir.


RESULTS
Plasma lipoprotein levels were quantified in 93 HIV-infected adults receiving PIs. Comparison was done with pretreatment values and with 28 nonPI-treated HIV-infected subjects. An elevation in plasma cholesterol 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). Plasma HDL-cholesterol levels remained unchanged. Combination of ritonavir or nelfinavir with saquinavir did not further elevate plasma lipid levels. A 48% increase in plasma levels of lipoprotein(a) was detected in PI-treated subjects 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 and premature atherosclerosis due to PI-associated dyslipidemia remains to be established.
Périard
D
D
Division of Infectious Diseases, Department of Pediatrics CHUV University Hospital, Lausanne, Switzerland.
Telenti
A
A
Sudre
P
P
Cheseaux
J J
JJ
Halfon
P
P
Reymond
M J
MJ
Marcovina
S M
SM
Glauser
M P
MP
Nicod
P
P
Darioli
R
R
Mooser
V
V
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000209:etiology*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000453:epidemiology; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000453:epidemiology; D019469:Indinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013972:Thyrotropin / Q000097:blood
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D008055:Lipids; D017270:Lipoprotein(a); D008074:Lipoproteins; D019469:Indinavir; D013972:Thyrotropin; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir