To evaluate the pharmacokinetics and pharmacogenomics of efavirenz (EFV) and lopinavir/ritonavir (LPV/RTV) in HIV-infected persons requiring hemodialysis.
Prospective, observational study of HIV-infected hemodialysis subjects receiving one 600mg tablet daily of EFV (N=13) or three 133.3/33.3mg capsules twice daily of LPV/RTV (N=13).
24-hour EFV and 12-hour LPV/RTV pharmacokinetics were assessed. Geometric mean ratios were calculated using historical controls with normal renal function. The effects of several candidate gene polymorphisms were also explored.
The geometric mean (95% CI, %CV) Cmin, Cmax, and AUC for the EFV group were 1.81µg/mL (0.93, 3.53; 103%), 5.04µg/mL (3.48, 7.29; 72%), and 71.5µg·h/mL (43.2, 118.3; 93%), respectively. These parameters were 2.76µg/mL (1.86, 4.11; 53%), 8.45µg/mL (6.41, 11.15; 52%), and 69.6µg·h/mL (55.6, 87.2; 37%) for LPV and 0.08µg/mL (0.05, 0.14; 63%), 0.58µg/mL (0.44, 0.76; 41%), and 3.74µg·h/mL (2.91, 4.80; 37%) for RTV. The AUC geometric mean ratios (90% CI) for EFV, LPV, and RTV were 132% (89, 197), 81% (67, 97), and 92% (76, 111), respectively. LPV Cmin was lower than expected in the hemodialysis group. Higher EFV concentrations were associated with the CYP2B6 516G>T polymorphism.
The pharmacokinetics of EFV and LPV/RTV in hemodialysis suggest that no dosing adjustments are necessary in treatment-naïve patients. As HIV-infected hemodialysis patients are disproportionately black, the increased frequency of the CYP2B6 516G>T polymorphism may lead to higher EFV levels. The potentially lower LPV trough levels in this population suggest that LPV/RTV should be used with caution in protease inhibitor-experienced patients.