Lopinavir Concentrations Do Not Differ between African-Americans and Caucasians

African-Americans using antiretroviral therapy have worse outcomes than Caucasians. The differences between racial groups are multiply-determined but may include differential metabolizing enzyme activity leading to altered drug exposure.

In the current study, researchers at Abbott Laboratories and the University of North Carolina, Chapel Hill, NC, compared the pharmacokinetics (PK) of once daily lopinavir/ritonavir (LPV/r) in HIV+ African-Americans and Caucasians.

This was a prospective, single-arm study enrolling 29 HIV+ ART-naïve African-Americans administered once daily regimen of soft-gel lopinavir/ritonavir (LPV/r) 800mg/200mg, tenofovir (TDF) 300mg and lamivudine (3TC) 300mg x 48 weeks.

Week 4 24h LPV PK was compared to 24h PK data from 18 HIV+ Caucasians in QD arm of Abbott 418, a clinical trial of the same agents at identical doses and frequency. LPV concentrations were analyzed with validated LC/UV method and noncompartmental PK parameters calculated (WinNonlin). Linear mixed model was used to compare LPV concentrations between studies. HIV RNA, CD4 count, fasting lipids, whole body DEXA and electronic adherence monitoring were performed among African-Americans.

Results

Median entry data among African-Americans (30% women): age = 36 years, CD4 = 169/uL, HIV RNA = 92,308 c/mL and BMI = 24.6 kg/m2.

For Caucasian subjects (11% women) median age = 38 years, CD4 = 144/uL, HIV RNA = 177,644 c/mL and BMI = 23.7 kg/m2.

LPV exposure (AUC24, Cmax and C24h) was not significantly different between African-Americans and Caucasians (p=0.55).

From baseline to week 4, median HIV RNA change was -5.0 log10 and median CD4 change was 59 cells/mL.

The authors conclude, "There was no significant difference in LPV exposure when administered once daily with TDF and 3TC among HIV+ African-Americans and Caucasians. Further, this regimen was found to be potent, well-accepted and well-tolerated among African-Americans.

The University of North Carolina, Infectious Diseases, Chapel Hill, United States, Tricounty Community Health Center, Newton Grove, United States, HealthServe Community Health Center, Greensboro, United States, Northwestern University, Infectious Diseases, Chicago, United States, The University of North Carolina, Medicine, Chapel Hill, United States, The University of North Carolina, Biostatistics, Chapel Hill, United States, Abbott Laboratories, Abbott Park, United States, The University of North Carolina, Pharmacology, Chapel Hill, United States.

08/25/06

Reference
D Wohl, P Menezes, R Torres, and others. Lopinavir concentrations do not differ between African-Americans and Caucasians administered once daily HIV therapy. The AAQD Study. 16th International AIDS Conference. August 13-18, 2006. Toronto, Canada. Abstract TUPE0096.