2012•JAIDS Journal of Acquired Immune Deficiency SyndromesOpen access
N348I in HIV-1 Reverse Transcriptase Counteracts the Synergy Between Zidovudine and Nevirapine
Soo Huey Yap, Brian D. Herman, Jessica Radzio, Nicolas Sluis‐Cremer, Gilda Tachedjian
Open full text 7 citations
Abstract
The efficacy of regimens that include both zidovudine and nevirapine can be explained by the synergistic interactions between these drugs. N348I in HIV-1 reverse transcriptase confers decreased susceptibility to zidovudine and nevirapine. Here, we demonstrate that N348I reverses the synergistic inhibition of HIV-1 by zidovudine and nevirapine. Also, the efficiency of zidovudine-monophosphate excision in the presence of nevirapine is greater for N348I HIV-1 reverse transcriptase compared with the wild-type enzyme. These data help explain the frequent selection of N348I in regimens that contain zidovudine and nevirapine, and suggest that the selection of N348I should be monitored in resource-limited settings where these drugs are routinely used.