Description

Lopinavir/ritonavir (trade name Kaletra) is a fixed-dose combination of two antiviral drugs, lopinavir and ritonavir. It is a highly effective treatment for HIV-1 infection. Lopinavir is the primary active component, and it belongs to the class of drugs known as protease inhibitors. Ritonavir, also a protease inhibitor, is included in this combination at a low dose not for its own antiviral effect, but as a “pharmacokinetic booster.”

Indication

Lopinavir/ritonavir is indicated for the treatment of HIV-1 infection in adults and pediatric patients (typically 6 months of age and older). It is used in combination with other antiretroviral agents as part of a highly active antiretroviral therapy (HAART) regimen. This combination is effective for both treatment-naïve patients and those who have previously been treated with other antiretroviral drugs.

While it was once a cornerstone of first-line therapy, its use has shifted in recent years due to the availability of newer, often more convenient and better-tolerated drugs. However, it remains an important option, particularly in patients with pre-existing resistance to other protease inhibitors.

Mechanism of Action

The mechanism of action of lopinavir/ritonavir involves the inhibition of the HIV protease enzyme, a critical component of the virus’s life cycle. The two components work together to achieve this effect:

1. Lopinavir’s Antiviral Action:
   • Lopinavir is the primary antiviral agent. It is a protease inhibitor that specifically targets the HIV-1 protease enzyme.

• • This enzyme is essential for the virus to mature and become infectious. After the virus’s genes are transcribed into a long polypeptide chain (known as a “polyprotein”), HIV protease is responsible for “cleaving” or cutting this long chain into smaller, functional proteins (like Gag, Pol, and others).

• • Lopinavir binds to the active site of the HIV protease, preventing it from performing this cleavage.

• • As a result, the virus produces only immature, defective, and non-infectious viral particles, which cannot go on to infect new cells.

2. Ritonavir’s Boosting Action:
   • Ritonavir is included at a low dose for a completely different purpose. It is a potent inhibitor of a specific human liver enzyme called cytochrome P450 3A4 (CYP3A4).

• • This enzyme is responsible for metabolizing and clearing many drugs, including lopinavir, from the body.

• • By inhibiting CYP3A4, ritonavir significantly slows the metabolism of lopinavir.

• • This “boosting” effect results in a much higher and more sustained concentration of lopinavir in the bloodstream, allowing it to exert its full antiviral effect while reducing the required dosage and frequency of administration. This is crucial because lopinavir, when administered alone, has poor oral bioavailability and is rapidly cleared from the body.