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The “Connection” Between HIV Drug Resistance and RNase H
Viral Mutation Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
Present address: Meso Scale Diagnostics, LLC, Gaithersburg, Maryland 20877, USA.
* Author to whom correspondence should be addressed.
Received: 21 June 2010; in revised form: 20 July 2010 / Accepted: 20 July 2010 / Published: 21 July 2010
Abstract: Currently, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are two classes of antiretroviral agents that are approved for treatment of HIV-1 infection. Since both NRTIs and NNRTIs target the polymerase (pol) domain of reverse transcriptase (RT), most genotypic analysis for drug resistance is limited to the first ~300 amino acids of RT. However, recent studies have demonstrated that mutations in the C-terminal domain of RT, specifically the connection subdomain and RNase H domain, can also increase resistance to both NRTIs and NNRTIs. In this review we will present the potential mechanisms by which mutations in the C-terminal domain of RT influence NRTI and NNRTI susceptibility, summarize the prevalence of the mutations in these regions of RT identified to date, and discuss their importance to clinical drug resistance.
Keywords: connection subdomain; NRTI; NNRTI; RNase H; drug resistance; HIV
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Delviks-Frankenberry, K.A.; Nikolenko, G.N.; Pathak, V.K. The “Connection” Between HIV Drug Resistance and RNase H. Viruses 2010, 2, 1476-1503.
Delviks-Frankenberry KA, Nikolenko GN, Pathak VK. The “Connection” Between HIV Drug Resistance and RNase H. Viruses. 2010; 2(7):1476-1503.
Delviks-Frankenberry, Krista A.; Nikolenko, Galina N.; Pathak, Vinay K. 2010. "The “Connection” Between HIV Drug Resistance and RNase H." Viruses 2, no. 7: 1476-1503.