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Virus Res. 2008 Jun;134(1-2):147-56. doi: 10.1016/j.virusres.2008.01.002. Epub 2008 Mar 26.

Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors.

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  • 1Division of Infectious Diseases, University of Pittsburgh School of Medicine, S817 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.


The non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are a therapeutic class of compounds that are routinely used, in combination with other antiretroviral drugs, to treat HIV-1 infection. NNRTIs primarily block HIV-1 replication by preventing RT from completing reverse transcription of the viral single-stranded RNA genome into DNA. However, some NNRTIs, such as efavirenz, have been shown to inhibit the late stages of HIV-1 replication by interfering with HIV-1 Gag-Pol polyprotein processing, while others, such as the pyrimidinediones, have been shown to inhibit both HIV-1 RT-mediated reverse transcription and HIV-1/HIV-2 viral entry. Accordingly, in this review we describe the multiple mechanisms by which NNRTIs inhibit HIV-1 reverse transcription (and in some cases HIV-2 reverse transcription) and other key steps involved in HIV-1/HIV-2 replication.

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