zidovudine (azt) monotherapy selects for the a360v mutation in the connection domain of hiv-1 reverse transcriptase齐多夫定(azt)单方选择a360v突变在连接域的hiv - 1逆转录酶.pdf

Zidovudine (AZT) Monotherapy Selects for the A360V Mutation in the Connection Domain of HIV-1 Reverse Transcriptase 1 1,2 1 1 3 Jessica H. Brehm , Yanille Scott , Dianna L. Koontz , Steven Perry , Scott Hammer , David 4 1 1 Katzenstein , John W. Mellors , Nicolas Sluis-Cremer *, for the AIDS Clinical Trials Group Study 175 Protocol Team 1 Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America, 2 Department of Infectious Disease and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America, 3 Columbia University Medical Center, New York, New York, United States of America, 4 Division of Infectious Diseases, Center for AIDS Research, Stanford, California, United States of America Abstract Background: We previously demonstrated in vitro that zidovudine (AZT) selects for A371V in the connection domain and Q509L in ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) which, together with the thymidine analog mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V, Q509L or other mutations in the C- terminal domains of HIV-1 RT. Methodology/Principal Findings: Full-length RT sequences in plasma obtained pre- and post-therapy were compared in 23 participants who received AZT monotherapy from the AIDS Clinical Trials Group study 175. Five of the 23 participants reached a primary study endpoint. Mutations significantly