Reynolds Steven J, Laeyendecker Oliver, Nakigozi Gertrude, Gallant Joel E, Huang Wei, Hudelson Sarah E, Quinn Thomas C, Newell Kevin, Serwadda David, Gray Ronald H, Wawer Maria J, Eshleman Susan H
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
AIDS Res Hum Retroviruses. 2012 Dec;28(12):1739-44. doi: 10.1089/aid.2011.0352. Epub 2012 Apr 26.
We analyzed antiretroviral drug susceptibility in HIV-infected adults failing first- and second-line antiretroviral treatment (ART) in Rakai, Uganda. Samples obtained from participants at baseline (pretreatment) and at the time of failure on first-line ART and second-line ART were analyzed using genotypic and phenotypic assays for antiretroviral drug resistance. Test results were obtained from 73 samples from 38 individuals (31 baseline samples, 36 first-line failure samples, and six second-line failure samples). Four (13%) of the 31 baseline samples had mutations associated with resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively). Among the 36 first-line failure samples, 31 (86%) had NNRTI resistance mutations and 29 (81%) had lamivudine resistance mutations; only eight (22%) had other NRTI resistance mutations. None of the six individuals failing a second-line protease inhibitor (PI)-based regimen had PI resistance mutations. Six (16%) of the participants had discordant genotypic and phenotypic test results. Genotypic resistance to drugs included in first-line ART regimens was detected prior to treatment and among participants failing first-line ART. PI resistance was not detected in individuals failing second-line ART. Surveillance for transmitted and acquired drug resistance remains a priority for scale-up of ART.
我们分析了乌干达拉凯地区接受一线和二线抗逆转录病毒治疗(ART)失败的HIV感染成人的抗逆转录病毒药物敏感性。使用抗逆转录病毒药物耐药性的基因分型和表型分析方法,对参与者在基线(治疗前)、一线ART失败时和二线ART失败时采集的样本进行了分析。检测结果来自38名个体的73个样本(31个基线样本、36个一线治疗失败样本和6个二线治疗失败样本)。31个基线样本中有4个(13%)存在与对核苷类或非核苷类逆转录酶抑制剂(分别为NRTIs和NNRTIs)耐药相关的突变。在36个一线治疗失败样本中,31个(86%)有NNRTI耐药突变,29个(81%)有拉米夫定耐药突变;只有8个(22%)有其他NRTI耐药突变。在接受基于二线蛋白酶抑制剂(PI)方案治疗失败的6名个体中,没有一人有PI耐药突变。6名(16%)参与者的基因分型和表型检测结果不一致。在治疗前以及一线ART治疗失败的参与者中检测到对一线ART方案中所含药物的基因耐药性。在二线ART治疗失败的个体中未检测到PI耐药性。对传播性和获得性耐药性的监测仍然是扩大ART治疗规模的优先事项。