目的了解2008年北京市未经抗病毒治疗HIV-1感染者中耐药株传播水平，为耐药监测和临床抗病毒治疗工作提供本底资料。方法参照WHO提出的HIV耐药警戒线调查方法（HIV drug resistance threshold survey，HIVDR－TS）指导方案，收集6个月...目的了解2008年北京市未经抗病毒治疗HIV-1感染者中耐药株传播水平，为耐药监测和临床抗病毒治疗工作提供本底资料。方法参照WHO提出的HIV耐药警戒线调查方法（HIV drug resistance threshold survey，HIVDR－TS）指导方案，收集6个月内检测发现的60～70名小于25岁的感染者血浆样本，检测HIV－1 pol区亚型及耐药基因型，并计算耐药株检出率、评价传播水平。结果61份符合要求的样本共获得50个有效pol区序列。感染途径以同性传播为主，占62％；亚型分布以B（42％）、CRF01_AE（28％）、CRF07_BC（26％）3种为主。出现1例针对PI类药物的耐药突变株，检出率为2％（1／50）；出现1例针对NRTI类药物的耐药突变株，检出率为2％（1／50）；未出现针对NNRTI类药物的耐药突变株，检出率为0。蛋白酶（PR）区和逆转录酶（RT）区的耐药突变株检出率均为2％，均属于低度传播范围（〈5％）。结论北京市未经抗病毒治疗HIV-1感染者中出现PR和RT区的耐药突变株，传播水平尚处于低流行状态，现有的抗病毒治疗方案是可行的，治疗前尚不需要进行大规模耐药性检测。展开更多
VRC01,a broadly neutralizing monoclonal antibody(bnmAb),can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120.We have previously demonstrated the presence of VRC0...VRC01,a broadly neutralizing monoclonal antibody(bnmAb),can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120.We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy.Here,we report follow-up studies of two subsequent samples from the same patient.With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope,we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy.Consistent with our previous observation,the resistant phenotype was associated with a single asparagine residue at position 460(N460),a potential N-linked glycosylation site in the V5 region.The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01.展开更多
文摘目的 分离培养体外稳定传代的原代HIV-1耐药毒株,观察失去药物压力下,耐药毒株的体外生长以及主要耐药突变的演化趋势.方法 采集15例服用拉米夫定＋司他夫定＋萘韦拉平（3TC＋D4T＋NVP）的HIV-1感染者的外周血单个核细胞（PBMC）,用体外共培养的方法从中分离原代HIV-1毒株;RT-PCR扩增耐药毒株历代培养上清的HIV-1 pol区基因并测序,在Stanford HIV Drug Resistance Database数据库进行耐药性分析.结果 15例患者中病毒载量〉1000拷贝/ml的有8例,均成功分离出稳定传代的原代毒株,其中2株为耐药毒株,所携带的主要耐药突变分别是K103N/K238T和M184V/K103N/Y181C/H221Y,分别对NVP和3TC/NVP高度耐药;无药物压力的体外培养过程中,M184V、K103N、Y181C和H221Y等耐药突变可以稳定传代,但是K238T发生了回复突变.结论 分离出2株稳定传代的HIV-1耐药毒株,无药物压力情况下,携带K103N突变的毒株具有较好的复制适应性,可稳定传代;携带M184V和K103N/Y181C/H221Y的毒株也能够稳定复制;本研究中发现K238T耐药突变在失去药物的条件下稳定性差,提示该位点易发生回复突变.
基金supported by the National Grand Program on Key Infectious Disease Control(2012ZX10001-006,2012ZX10001-009 and 2012ZX10001-003)the National Outstanding Youth Award(30825035)+1 种基金the National Natural Science Foundation of China(81101236)the Tsinghua University Initiative Scientific Research Program
文摘VRC01,a broadly neutralizing monoclonal antibody(bnmAb),can neutralize a diverse array of HIV-1 isolates by mimicking CD4 binding to the envelope glycoprotein gp120.We have previously demonstrated the presence of VRC01-resistant strains in an HIV-1 infected patient during antiretroviral therapy.Here,we report follow-up studies of two subsequent samples from the same patient.With genetic and phenotypic analysis of over 70 full-length molecular clones of the HIV-1 envelope,we show that VRC01-resistant HIV-1 continued to exist and change in its proportion of the infecting virus during treatment with a highly active antiretroviral therapy.Consistent with our previous observation,the resistant phenotype was associated with a single asparagine residue at position 460(N460),a potential N-linked glycosylation site in the V5 region.The persistence and continuing evolution of VRC01-resistant HIV-1 in vivo presents a great challenge to our future preventative and therapeutic interventions based on VRC01.
