Description

Lamivudine, also known as 3TC, is an oral antiviral drug that belongs to the class of nucleoside reverse transcriptase inhibitors (NRTIs). It is a synthetic nucleoside analogue of cytidine. Lamivudine is notable for its activity against both the Human Immunodeficiency Virus (HIV) and the Hepatitis B Virus (HBV).

Indication

Lamivudine is indicated for the treatment of:

• HIV-1 Infection: It is used in combination with other antiretroviral agents to treat HIV-1 infection in adults and children. It is not used as a monotherapy for HIV due to the rapid development of resistance.

• Chronic Hepatitis B Virus (HBV) Infection: It is also used to treat chronic HBV infection in adults and children who have evidence of viral replication and active liver inflammation.

It’s important to note that the dosage of lamivudine for HIV is higher than the dosage for HBV. Patients who are co-infected with both viruses should be treated with the higher dose appropriate for HIV.

Mechanism of Action

Lamivudine’s antiviral effect is based on its ability to inhibit viral DNA synthesis. The process is as follows:

1. Phosphorylation: Upon administration, lamivudine is taken up by infected cells and undergoes a series of phosphorylation steps by cellular kinases. This converts it into its active, triphosphate form, lamivudine triphosphate (3TC-TP).

2. Competitive Inhibition: Lamivudine triphosphate acts as a competitive inhibitor of the viral DNA polymerase. It competes with the natural substrate, deoxycytidine triphosphate (dCTP), for incorporation into the viral DNA. The viral enzymes involved are the HIV reverse transcriptase and the HBV DNA polymerase.

3. DNA Chain Termination: Once lamivudine triphosphate is incorporated into the growing viral DNA chain, it acts as a chain terminator. This is because it lacks a necessary hydroxyl group at the 3′ position, which is required to form the phosphodiester bond for the next nucleotide to be added. This premature termination of the DNA chain halts viral replication.

The drug’s specificity for viral enzymes over human DNA polymerases makes it effective at inhibiting viral replication with fewer side effects on the host’s cellular DNA synthesis. However, a major limitation of lamivudine, particularly when used for HBV, is the relatively high rate of viral resistance that can develop with long-term use.