Impact of various antiretroviral drugs and their plasma concentrations on plasma lipids in heavily pretreated HIV-infected patients.
OBJECTIVE
To evaluate the frequency and the magnitude of lipid abnormalities (LA) in respect to the nature of the antiretroviral drug and its plasma concentrations.


METHODS
Trough concentrations (C(trough)) of protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) were assessed at Weeks 4, 8, 24, 28, and 32. Fasting triglycerides (TG) and total cholesterol (CH) were sampled at Weeks 0, 12, 20, and 32. We analyzed the probability of occurrence of grade 3-4 CH (> 7.8 mmol/L) and TG (> 8.4 mmol/L) during a 24-week period according to the drug taken using a Kaplan-Meier analysis and log rank test. Relation between Week 8 PI or NNRTI C(trough) and Week 12 lipid levels was assessed using the Kendall correlation measure.


RESULTS
The PharmAdapt study included 252 patients (mean age 41 years, 83% males); the patients received a PI (73%), an NNRTI (50%), and/or a ritonavir (RTV) booster-containing (46%) regimen. Compared to any other regimen, use of lopinavir (LPV)/RTV or efavirenz (EFV) was associated with a higher risk of grade 3-4 CH. Use of LPV/RTV and RTV booster was associated with a higher risk of grade 3-4 TG. Use of any PI-containing regimen was associated with a higher risk for grade 3-4 CH and TG compared to non PI-based regimens. Kendall correlation coefficients for PI or NNRTI C(trough) and blood lipid levels were close to zero for all drugs and CH or TG, showing the absence of relation between drug concentrations and lipid levels.


CONCLUSIONS
Severity of lipid abnormalities is related to the nature of the antiretroviral drug. There is no short-term relation between PI or NNRTI trough concentrations and blood lipid levels in heavily pretreated patients.
Department of Infectious Diseases, CHU Bichat, Paris, France. clevenberghph@hotmail.com
P
P
Clevenbergh
R
R
Garraffo
P
P
Dellamonica
D000328:Adult; D000480:Alkynes; D048588:Benzoxazines; D002784:Cholesterol / Q000097:blood; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir; D008297:Male; D010078:Oxazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides; D061466:Lopinavir; D002784:Cholesterol; C098320:efavirenz; D019438:Ritonavir