Abstract:
:It was recently proposed that HIV RT mutations that decrease RNase H activity increase zidovudine (AZT) resistance by delaying the degradation of the RNA template, allowing more time for AZTMP excision from the 3' end of the viral DNA. This predicts that suboptimal concentrations of an RNase H Inhibitor (RNHI), which would decrease RNaseH activity, would decrease AZT susceptibility. Conversely, a suboptimal concentration of a nonnucleoside RT inhibitor (NNRTI) would decrease polymerase activity and increase AZT susceptibility. We determined the effect of several RNHIs and an NNRTI (nevirapine) on AZT and lamivudine (3TC) susceptibility with vectors that replicate using WT or AZT resistant RTs. Susceptibility to 3TC, which is not readily excised, did not change significantly. Nevirapine, and most RNHIs tested, had only small effects on the susceptibility of either HIV vector to AZT and 3TC. One RNHI, F0444-0019, increased the IC(50) for AZT for either vector by ~5-fold, which may be a concern.
journal_name
Virologyjournal_title
Virologyauthors
Davis CA,Parniak MA,Hughes SHdoi
10.1016/j.virol.2011.08.010subject
Has Abstractpub_date
2011-10-25 00:00:00pages
64-71issue
2eissn
0042-6822issn
1096-0341pii
S0042-6822(11)00365-5journal_volume
419pub_type
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