Description

Tenofovir disoproxil (TD) is a widely used oral prodrug of the nucleotide analogue tenofovir. It is often prescribed as its fumarate salt, tenofovir disoproxil fumarate (TDF), under brand names like Viread. As a prodrug, it is an inactive compound that is converted in the body to its active form, tenofovir, which then acts as an antiviral agent. It is classified as a nucleoside reverse transcriptase inhibitor (NRTI).

Indication

Tenofovir disoproxil 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 (typically 2 years of age and older). It is not used as a monotherapy for HIV due to the risk of resistance development.

• Chronic Hepatitis B Virus (HBV) infection: It is indicated for the treatment of chronic hepatitis B in adults and children (typically 2 years of age and older) who have evidence of active viral replication and signs of active liver disease.

It’s important to note that before initiating treatment with tenofovir disoproxil, patients should be tested for both HIV and HBV infection.

Mechanism of Action

Tenofovir disoproxil works by inhibiting viral replication through a multi-step process:

1. Conversion to Tenofovir: After oral administration, tenofovir disoproxil is absorbed from the gut and rapidly hydrolyzed (broken down) into its active parent compound, tenofovir.

2. Phosphorylation: Tenofovir is then transported into cells, where it undergoes two successive phosphorylation steps by cellular kinases. This converts it into its active antiviral form, tenofovir diphosphate (tenofovir-DP).

3. Inhibition of Viral Reverse Transcriptase/DNA Polymerase: Tenofovir diphosphate is an analogue of deoxyadenosine triphosphate (dATP), a natural building block of DNA. It acts as a potent competitive inhibitor of the viral enzymes essential for replication:

• • HIV Reverse Transcriptase: This enzyme converts the virus’s RNA genome into DNA, a crucial step for the virus to integrate into the host cell’s DNA.

• • HBV DNA Polymerase: This enzyme is responsible for synthesizing the DNA genome of the hepatitis B virus.

4. DNA Chain Termination: By competing with dATP, tenofovir diphosphate is incorporated into the growing viral DNA chain. However, because it lacks a necessary 3′-hydroxyl group, it prevents the addition of any further nucleotides. This causes premature termination of the viral DNA chain, effectively halting the replication of the virus and reducing the viral load.

Tenofovir is known for its high genetic barrier to resistance, making it a cornerstone of treatment for both HIV and HBV.