HIV-1 sensitivity to zidovudine and clinical outcome in children
HIV-1 sensitivity to zidovudine and clinical outcome in children
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儿童 HIV-1 对齐多夫定的敏感性和临床结果
DOI：
10.1016/0140-6736(92)90140-x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
E. Connor
中科院分区：
文献类型：
--
作者：
G. Tudor;R. McKinney;E. Walter;S. Santacroce;Karen O'Donnell;Wilfert Cm;T. Rudoll;M. H. S. Clair;M. Maha;C. Vavro;M. Mintz;E. Connor
在患有获得性免疫缺陷综合征的成人中，齐多夫定长期单药治疗选择了对药物体外敏感性显著降低的人类免疫缺陷病毒1型（HIV-1）毒株。我们评估了齐多夫定体外耐药与儿童临床结局之间的关系，儿童疾病进展比成人更快。我们研究了23名儿童与HIV-1疾病的症状，在延长单药治疗齐多夫定。使用体外测定法测定治疗9至39个月后获得的抑制50%病毒分离株复制所需的齐多夫定浓度（IC 50）。从19名儿童中获得了足够高滴度的病毒储备液，以产生可重现的结果。在接下来的6个月的治疗中，9名儿童病情稳定，7名恶化，3名死亡。齐多夫定敏感性降低与不良临床结局之间存在高度显著相关性（p<0.001），但IC 50与开始治疗时的年龄或治疗时间长短无关。在齐多夫定IC 50升高的病毒分离株的儿童中，治疗开始时（p= 0.02）和采样时（p= 0.01），经校正的CD 4淋巴细胞计数较低。初始血清p24抗原水平不能预测随后出现的耐药病毒，但在病毒敏感性采样时，较高的p24抗原水平与IC 50升高相关（p=0·004）。研究结果表明，根据临床标准判断，大多数对齐多夫定单药治疗无反应的儿童对该药物的体外敏感性会发生变化。在这些儿童中，应考虑替代抗逆转录病毒疗法。
In adults with the acquired immunodeficiency syndrome, long-term monotherapy with zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with substantially reduced in-vitro susceptibility to the drug. We have assessed the relation between in-vitro resistance to zidovudine and clinical outcome in children, in whom disease progression is more rapid than in adults. We studied 23 children with symptoms of HIV-1 disease during extended monotherapy with zidovudine. An in-vitro assay was used to determine the concentration of zidovudine required to inhibit by 50% the replication of viral isolates (IC50) obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to yield reproducible results were obtained from 19 of the children. During the following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3 died. There was a highly significant relation between decreased zidovudine susceptibility and poor clinical outcome (p<0·001) but no relation between IC50and age at start of therapy or length of time on treatment. Age-adjusted CD4 lymphocyte counts were lower at the start of treatment (p=0·02) and at the time of sampling (p=0·01) in children whose viral isolates had an increased zidovudine IC50. Initial serum p24 antigen levels were not predictive of subsequent emergence of resistant virus, but at the time of sampling for viral sensitivity higher p24 antigen levels were associated with raised IC50(p=0·004). The findings suggest that most children who become unresponsive to monotherapy with zidovudine, as judged by clinical criteria, will have changes in in-vitro sensitivity to the drug. In these children, an alternative antiretroviral therapy should be considered.
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CD4 计数和接受抗逆转录病毒治疗的 HIV 感染患者的死亡风险。
影响因子：
39.2
作者：
Yarchoan,R;Venzon,DJ;Pluda,JM;Lietzau,J;Wyvill,KM;Tsiatis,AA;Steinberg,SM;Broder,S
通讯作者：
Broder,S
影响因子：
56.9
作者：
LARDER, BA;DARBY, G;RICHMAN, DD
通讯作者：
RICHMAN, DD
疾病阶段和药物剂量对人类免疫缺陷病毒分离株齐多夫定敏感性的影响。
DOI：
--
发表时间：
1990
期刊：
Journal of acquired immune deficiency syndromes
影响因子：
--
作者：
Richman,DD;Grimes,JM;Lagakos,SW
通讯作者：
Lagakos,SW
影响因子：
39.2
作者：
MASUR, H;OGNIBENE, FP;LANE, HC
通讯作者：
LANE, HC