Abacavir plasma pharmacokinetics in the absence and presence of atazanavir/ritonavir or lopinavir/ritonavir and vice versa in HIV-infected patients

BACKGROUND: Significant interactions between abacavir and other antiretrovirals have not been reported. This study investigated the steady-state plasma pharmacokinetics of abacavir when co-administered with atazanavir/ritonavir or lopinavir/ritonavir in HIV-infected individuals. METHODS: HIV-infected subjects on abacavir (600 mg once daily) plus two nucleoside reverse transcriptase inhibitors (NRTIs) (excluding tenofovir) underwent a 24 h pharmacokinetic assessment for plasma abacavir concentrations. Atazanavir/ritonavir (300/100 mg once daily; arm (1) or lopinavir/ritonavir (400/100 mg twice daily; arm (2) were then added and the 24 h pharmacokinetic assessment repeated. Arm 3 included subjects stable on atazanavir/ritonavir or lopinavir/ritonavir and two NRTIs (excluding tenofovir or abacavir). These patients underwent a pharmacokinetic assessment for atazanavir/ritonavir or lopinavir/ritonavir concentrations on day 1, abacavir (600 mg once daily) was then added to the regimen and the pharmacokinetic assessment repeated. Within-subject changes in drug exposure were evaluated by geometric mean (GM) ratios and 95% confidence intervals (CI). RESULTS: Twenty-four patients completed the study. GM (95% CI) abacavir area under the curve (AUC) was 18,621 (15,900-21,807) and 15,136 (13,339-17,174) ng.h/ml without and with atazanavir/ritonavir and 15,136 (12,298-18,628) and 10,471 (9,270-11,828) ng.h/ml without and with lopinavir/ritonavir. GM (95% CI) atazanavir AUC without and with abacavir was 26,915 (13,252-54,666) and 28,840 (19,213-43,291) ng.h/ml; lopinavir AUC without and with abacavir was 60,253 (48,084-75,509) and 63,096 (48,128-82,718) ng.h/ml. CONCLUSIONS: No changes in atazanavir or lopinavir exposures were observed following the addition of abacavir; however, decreases in abacavir plasma exposure of 17% and 32% were observed following the addition of atazanavir/ritonavir or lopinavir/ritonavir, respectively.