Indications
Efavirenz is indicated for use in combination therapy for the treatment of HIV infection. Originally approved for patients who had not responded to zidovudine therapy, it is now recommended by the CDC to be part of a three-drug regimen. This regimen typically includes another nucleoside reverse transcriptase inhibitor, such as lamivudine, stavudine, or zidovudine, paired with either a protease inhibitor or efavirenz, to effectively manage HIV infection, whether innate or acquired immunodeficiency syndrome (AIDS).
Pharmacodynamics
Efavirenz is classified as a non-nucleoside reverse transcriptase inhibitor (NNRTI) and shares a synthetic purine derivative structure. It functions by inhibiting the reverse transcriptase enzyme, which is crucial for the replication of the HIV virus. This mechanism of action allows it to supress the viral replication process. Efavirenz was subsequently recognized as a viable treatment option for patients demonstrating resistance to earlier therapies, providing an essential alternative in HIV management protocols.
Metabolism
Efavirenz undergoes primary metabolism through the cytochrome P450 enzyme system, which converts it into hydroxylated metabolites. These metabolites then undergo further glucuronidation. Importantly, these resultant hydroxylated compounds do not exhibit significant in vitro activity against HIV-1, indicating that the antiretroviral efficacy of efavirenz is predominantly associated with the parent drug rather than its metabolites.
Mechanism of Action
Efavirenz functions by inhibiting the activity of viral RNA-directed DNA polymerase, commonly known as reverse transcriptase. Its antiviral effectiveness relies on intracellular conversion to its active triphosphorylated form, with phosphorylation rates varying depending on cell type. By hindering reverse transcriptase, efavirenz disrupts the formation of DNA copies of viral RNA, which are crucial for the synthesis of new virions. Intracellular enzymes subsequently degrade the HIV particles that have been uncoated and left vulnerable upon entering the host cell. As a result, reverse transcriptase inhibitors, including efavirenz, exhibit virustatic properties, meaning they do not completely remove HIV from the body. While human DNA polymerase displays reduced susceptibility to the triphosphorylated form of efavirenz, some of the drug's toxicity may still be attributed to this mechanism.
