Lopinavir/ritonavir (ABT-378/r)

Area of Science:

• Pharmacology
• Virology
• Drug Development

Background:

• Human Immunodeficiency Virus (HIV) eradication remains elusive despite advances.
• Current antiretroviral (ARV) therapy achieves viral suppression, reducing opportunistic infections and malignancies.
• Existing protease inhibitors (PIs) face challenges like poor pharmacokinetics and drug interactions, potentially leading to resistance.

Purpose of the Study:

• To introduce lopinavir/ritonavir (LPV/r) as a novel ARV agent.
• To highlight the pharmacokinetic enhancement strategy of LPV/r.
• To evaluate the potential of LPV/r in maintaining viral suppression and preventing resistance.

Main Methods:

• LPV/r combines lopinavir with low-dose ritonavir, a cytochrome P450 (CYP) 3A4 inhibitor.
• Ritonavir boosts lopinavir levels by inhibiting its metabolism, leading to higher plasma concentrations.
• Pharmacokinetic studies correlate trough plasma concentrations (C(min)) with virological outcomes.

Main Results:

• LPV/r demonstrates a high lopinavir trough level to wild-type median effective concentration (EC(50)) ratio.
• The co-formulation shows good tolerability compared to other PIs.
• LPV/r achieves sufficient C(min) to suppress resistant viral strains and provides a barrier to new resistance.

Conclusions:

• LPV/r exemplifies successful pharmacokinetic enhancement for improved ARV therapy.
• The drug reduces pill burden and improves patient compliance.
• LPV/r shows promising results in both ARV-naive and experienced patients.