What is the mechanism of action of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

NRTIs interrupt the HIV replication cycle via competitive inhibition of HIV reverse transcriptase and termination of the DNA chain. [10] Reverse transcriptase is an HIV-specific DNA polymerase that allows HIV RNA to be transcribed into single-strand and ultimately double-strand proviral DNA and incorporated into the host-cell genome. Proviral DNA chain elongation is necessary before genome incorporation can occur and is accomplished by the addition of purine and pyrimidine nucleosides to the 3’ end of the growing chain.

NRTIs are structurally similar to the DNA nucleoside bases and become incorporated into the proviral DNA chain, resulting in termination of proviral DNA formation. [11] Tenofovir, lamivudine, and emtricitabine exhibit activity against hepatitis B virus (HBV) in addition to HIV and are frequently incorporated into antiretroviral regimens for patients with HIV and HBV coinfection. [8]


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