Nevirapine-resistant human immunodeficiency virus: Kinetics of replication and estimated prevalence in untreated patients
Nevirapine-resistant human immunodeficiency virus: Kinetics of replication and estimated prevalence in untreated patients
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DOI：
10.1128/jvi.70.11.7894-7899.1996
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发表时间：
1996-11-01
影响因子：
5.4
通讯作者：
Richman, DD
中科院分区：
文献类型：
--
作者：
Havlir, DV;Eastman, S;Richman, DD
非核苷类逆转录酶抑制剂奈韦拉平在体内快速选择突变型人类免疫缺陷病毒（HIV）。在接受单药治疗的患者中，最常见的突变发生在氨基酸残基181处。奈韦拉平治疗开始后，定期采集血浆和外周血单核细胞样本，测定HIV RNA水平和含有181位残基突变的病毒比例。HIV RNA水平在开始治疗后的前24小时内保持稳定，并在1至7天内迅速下降。在所有单药治疗受试者中，2周后血浆HIV RNA拷贝数相对于基线的最大降幅为2 log（10）/ml（范围：1.96 - 2.43）。HIV RNA的估计中位半衰期为1.11天（范围：0.63 - 1.61）。治疗14天后，HIV RNA水平开始升高，检测到181个突变病毒。新出现的病毒群体的估计倍增时间范围为1.80至5.73天。外周血单个核细胞中的病毒DNA从野生型转化为181位残基突变的突变体的速度明显慢于血浆中的HIV RNA。在两名受试者中，计算的181突变病毒干燥剂治疗的患病率为7和133/10，000血浆HIV RNA拷贝。
The nonnucleoside reverse transcriptase inhibitor nevirapine rapidly selects for mutant human immunodeficiency virus (HIV) in vivo. The most common mutation occurs at amino acid residue 181 in patients receiving monotherapy. After the initiation of nevirapine therapy, plasma and peripheral blood mononuclear cell samples were collected at frequent intervals and assayed for HIV RNA levels and the proportion of virus containing a mutation at residue 181. HIV RNA levels remained stable for the first 24 h after initiation of therapy and rapidly declined between 1 and 7 days. There was a consistent maximum decrease of 2 log(10) HIV RNA copies per ml of plasma (range, 1.96 to 2.43) from baseline after 2 weeks in all monotherapy subjects. The estimated median half-life of HIV RNA was 1.11 days (range, 0.63 to 1.61). After 14 days of therapy, HIV RNA levels began to increase and 181 mutant, virus was detected. The estimated doubling time of the emerging virus population ranged from 1.80 to 5.73 dags. Viral DNA in peripheral blood mononuclear cells turned over from wild type to the mutant with a mutation at residue 181 significantly more slowly than did HIV RNA in plasma. In two subjects, the calculated prevalence of the 181 mutant virus Drier to treatment was 7 and 133 per 10,000 copies of plasma HIV RNA.