Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors.
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.
Sluis-Cremer
Nicolas
N
Division of Infectious Diseases, University of Pittsburgh School of Medicine, S817 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA. cremern@dom.pitt.edu
Tachedjian
Gilda
G
D001665:Binding Sites; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D048348:Reverse Transcription / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase