Should We Include Connection Domain Mutations of HIV-1 Reverse Transcriptase in HIV Resistance Testing 英文参考文献.docVIP

Perspective Should We Include Connection Domain Mutations of HIV-1 Reverse Transcriptase in HIV Resistance Testing? Matthias G?tte D espite the remarkable achievements in discovery and development of antiretroviral Linked Research Article genotyping systems need to be seen as surrogates of the whole genome. For practical, technical, and economical reasons, most assays involve only portions of the drug target. Two classes of commonly used This Perspective discusses the following new study published inPLoS Medicine: agents for the treatment of infection with human immunode?ciency virus type 1 (HIV-1), drug resistance remains a major reason for viral rebound and treatment failure. Therefore, resistance testing has become an important tool in clinical decision making. HIV genotype testing, to look for mutations that confer drug resistance, is now widely established as the standard of care to guide treatment in the context of both primary infection and virological failure [1]. Phenotypic resistance testing involves drug susceptibility measurements in cell-based in vitro assays. Differences between wild type viral strains with no known resistance-conferring mutations and patient-derived HIV variants are usually expressed in drug concentrations required to inhibit Yap SH, Sheen CW, Fahey J, Zanin M, Tyssen D, et al. (2007) N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. PLoS Med 4(12): e335. doi:10.1371/journal.pmed.0040335 Analyzing HIV sequences from a Canadian cohort, Gilda Tachedjian and colleagues identify a common mutation in a little-studied domain of reverse transcriptase that confers resistance to two drug classes. antiretroviral drugs target RT, the enzyme that copies HIV’s RNA genome into DNA, leading to viral persistence in the host cell and ultimately to production of new HIV particles. Nucleoside analogue RT inhibitors (NRTIs), the ?rst of these drug classes, are incorporated into the DNA that is bei