Duwe S, Brunn M, Altmann D, Hamouda O, Schmidt B, Walter H, Pauli G, Kücherer C
Robert Koch-Institut, Berlin, Germany.
J Acquir Immune Defic Syndr. 2001 Mar 1;26(3):266-73. doi: 10.1097/00042560-200103010-00010.
Genotypic and phenotypic resistance of viral reverse transcriptase (RT) and protease (PR) was determined for 64 therapy-naive, HIV-1-infected seroconverters of the German Seroconverter Study coordinated by the Robert Koch-Institut, Berlin. The date of seroconversion of patients and the laboratory, clinical, and therapeutic follow-up data were documented. Samples were collected between 1996 and 1999. Phenotypic resistant HIV-1 were found in 8 (13%) seroconverters; in most cases resistance was weak and mainly directed against RT inhibitors (4 nucleoside reverse transcriptase inhibitors [NRTIs], 2 nonnucleoside reverse transcriptase inhibitors [NNRTIs], 1 combination NRTI/NNRTI). Only one infection with a weak PR inhibitor resistance was identified. Transmission of multidrug-resistant HIV-1 has not yet been observed. Frequently at least one or more amino acid mutations associated with antiretroviral drug resistance were detected by genotypic analysis. The mean number of resistance-associated mutations in the RT of the transmitted virus has increased significantly since 1996. Studies have shown the improved benefit of initial antiretroviral therapy if based on genotypic resistance data. In view of the considerably high level of transmission of resistant HIV-1 in Germany, which is also seen in other studies in Europe and the United States, we suggest determining the genotypic resistance pattern before starting therapy of newly HIV-1-infected patients.
针对由柏林的罗伯特·科赫研究所协调开展的德国血清转化者研究中的64名未接受过治疗、感染了HIV-1的血清转化者,测定了病毒逆转录酶(RT)和蛋白酶(PR)的基因型及表型耐药性。记录了患者的血清转化日期以及实验室、临床和治疗随访数据。样本采集于1996年至1999年期间。在8名(13%)血清转化者中发现了表型耐药的HIV-1;在大多数情况下,耐药性较弱,主要针对RT抑制剂(4种核苷类逆转录酶抑制剂[NRTIs]、2种非核苷类逆转录酶抑制剂[NNRTIs]、1种NRTI/NNRTI组合)。仅发现1例对PR抑制剂耐药性较弱的感染。尚未观察到多重耐药HIV-1的传播。通过基因型分析经常检测到至少一种或多种与抗逆转录病毒药物耐药性相关的氨基酸突变。自1996年以来,传播病毒RT中与耐药性相关的突变平均数量显著增加。研究表明,如果基于基因型耐药数据,初始抗逆转录病毒治疗的获益会有所改善。鉴于在德国耐药HIV-1的传播水平相当高,在欧洲和美国的其他研究中也有发现,我们建议在开始对新感染HIV-1的患者进行治疗前确定基因型耐药模式。