Impact of Kaletra on amprenavir plasma concentrations in HIV treatment-experienced patients

Kaletra (lopinavir/ritonavir) and amprenavir (APV) are both potent HIV protease inhibitors (PI) with demonstrated efficacy in salvage therapy. Few data are available on the combination of these two PIs and reciprocal drug-drug interaction remains unknown.

The objective of a French study presented at the 41st ICAAC was to assess APV and lopinavir/r plasma concentrations of this combination, and to compare to APV and lopinavir/r plasma concentrations with patients receiving only one of these PI.

Plasma PI Cmin were determined in consecutive patients receiving lopinavir/r (400/100mg BID) (n=11), APV + Ritonavir (RTV) (600/100mg BID) (n=36), lopinavir/r (400/100mg BID) + APV (600mg BID) (n=10), and lopinavir/r (400/100 mg BID) + APV (750 mg BID) (n=5).

All patients received two nucleoside analogues associated with APV and/or lopinavir/r, but none efavirenz (Sustiva) or nevirapine (Viramune). All plasma concentrations were determined by HPLC.

APV median Cmin were 1755 ng/ml [607-3066], 778 [190-2037], 998 [669-1670] in patients receiving APV+ RTV (600/100 BID), lopinavir/r + APV (600/BID), and lopinavir/r + APV (750 BID), respectively.

Lopinavir (LPV) median Cmin were respectively 3326 ng/ml [1316-6698], 2226 [518-8722] and 1716 [347-4810] in patients receiving lopinavir/r, lopinavir/r + APV 600 BID, lopinavir/r +APV 750 BID.

RTV median Cmin were 103 ng/ml [34-366] , 147 [ 80-519] , 91 [10-1399] , 154 [ 30-203] in patients receiving respectively APV/RTV , ABT 378/r , and ABT 378/ r + APV.

Plasma APV Cmin were decreased by more than 50% in patients receiving the combination of APV + lopinavir/r with significant difference (p<0.001 )in comparison with APV+ RTV (600/100 BID). Nevertheless, APV Cmin remained > 500 ng/ml in all patients except one. The impact of this interaction on the clinical efficacy of the combination remains to be investigated.

JL Meynard. Impact of ABT 378/r on the Amprenavir (APV) Plasma Concentrations in HIV-Experienced Patients Treated by the Association APV -ABT 378/r. Abstract I-1736 (poster).