Lopinavir/ritonavir: appraisal of its use in HIV therapy

Abstract

Recommendations for a highly active antiretroviral therapy in either pretreated patients or symptomatic patients with an AIDS-defining event include at least one protease inhibitor. The majority of currently available protease inhibitors are coadministrated with low-dose ritonavir, a pharmacoenhancer that significantly increases protease inhibitor plasma concentrations. In the class of protease inhibitors lopinavir plus ritonavir is the only coformulation. This coformulation was designed to overcome the problems of earlier agents of this class of drugs concerning unfavorable pharmacokinetics with a higher frequency of dosing and therapy failure. The pharmacoenhancing effect of ritonavir on lopinavir resulted in a highly potent, clinically effective antiretroviral drug with a high genetic barrier to viral resistance. Safety concerns have taken a backseat, focusing instead on the favorable efficacy of lopinavir, which recently led to the evaluation of its use in boosted double-protease-inhibitor regimens, as a once-daily application and even in HIV monotherapy. Nevertheless, since HIV infection became a chronic but controllable disease, side effects like metabolic disorders and cardiovascular disease have begun to draw increased attention in the long-term treatment with protease inhibitors. Coformulated lopinavir/ritonavir is available as a soft gelatin capsule (133.33/33.33 mg), liquid formulation (80/20 mg/ml) and recently approved melt-extrusion tablet (200/50 mg). Lopinavir/ritonavir is recommended for first- and second-line therapy in HIV-1 infection, in children as well as adolescents and adults.