Lopinavir

Lopinavir is a protease inhibitor used in the treatment of HIV-1 infection. It is commonly provided in fixed-dose combinations with ritonavir (brand names Kaletra, Aluvia) to boost lopinavir exposure by inhibiting the cytochrome P450 3A4 enzyme.

Mechanism of action: Lopinavir binds to and inhibits HIV-1 protease, an enzyme required for processing viral polyproteins. This prevents maturation of infectious virions, reducing viral replication.

Clinical use: Lopinavir/ritonavir is a component of combination antiretroviral therapy for HIV-1 infection in adults and children. In boosted regimens, it is used as a protease-inhibitor–based option that can be given twice daily or, in some cases, once daily. It is not active against HIV-2 and is typically part of regimens chosen based on efficacy, tolerability, and potential drug interactions.

Dosing and administration: The typical adult dose is lopinavir 400 mg with ritonavir 100 mg twice daily, taken with food to optimize absorption. Pediatric dosing is weight-based and also co-formulated with ritonavir; some regimens permit once-daily dosing in select patients. Because absorption increases with food, dosing should be taken with meals.

Adverse effects: Common adverse effects include diarrhea, nausea, vomiting, abdominal pain, and weight gain. Metabolic effects such as hyperlipidemia and insulin resistance, hepatotoxicity with elevated liver enzymes, pancreatitis, rash, and pruritus can occur. Cardiac effects may include PR and QT interval prolongation.

Drug interactions: Lopinavir/ritonavir strongly inhibits CYP3A4 and participates in many drug interactions. Coadministration with simvastatin or lovastatin is contraindicated due to increased statin exposure. Coadministration with other CYP3A4 substrates, inhibitors, or inducers requires careful management.

Resistance: Resistance can develop with poor adherence or prolonged viral replication, typically involving mutations in the HIV-1 protease gene and reducing susceptibility to lopinavir and some other protease inhibitors.