differential in vitro kinetics of drug resistance mutation acquisition in hiv-1 rt of subtypes b and c体外耐药性突变动力学微分收购的hiv - 1 rt亚型b和c.pdfVIP

Differential In Vitro Kinetics of Drug Resistance Mutation Acquisition in HIV-1 RT of Subtypes B and C 1 1 1 2 2 Rodrigo D. Cunha , Celina M. Abreu , Luis M. F. Gonzalez , Monique Nijhuis , Dorien de Jong , 1 1 1 1 Renato S. Aguiar , Adriana O. Afonso , Rodrigo M. Brindeiro , Amilcar Tanuri * ´ 1 Laboratorio de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil, 2 Department of Virology, Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands Abstract Background: HIV-1 subtype B is the most prevalent in developed countries and, consequently, it has been extensively studied. On the other hand, subtype C is the most prevalent worldwide and therefore is a reasonable target for future studies. Here we evaluate the acquisition of resistance and the viability of HIV-1 subtype B and C RT clones from different isolates that were subjected to in vitro selection pressure with zidovudine (ZDV) and lamivudine (3TC). Methods/Principal Findings: MT4 cells were infected with chimeric virus pseudotyped with RT from subtype B and C clones, which were previously subjected to serial passage with increasing concentrations of ZDV and 3TC. The samples collected after each passage were analyzed for the presence of resistance mutations and VL. No differences were found between subtypes B and C in viral load and resistance mutations when these viruses were selected with 3TC. However, the route of mutations and the time to rebound of subtype B and C virus were different when subjected to ZDV t