Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection
Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection
复制标题
DOI：
10.1086/422036
复制
发表时间：
2004-07-15
影响因子：
6.4
通讯作者：
Grant, RM
中科院分区：
文献类型：
--
作者：
Barbour, JD;Hecht, FM;Grant, RM
背景资料。感染原发耐药的人类免疫缺陷病毒1型(HIV-1)与药物初治患者中较高的CD4(+)T细胞计数有关，这表明与耐药性相关的病毒Poll复制能力(RC)的改变可以减轻体内的免疫损伤，而不依赖于药物的暴露。使用包含患者来源的HIV-1蛋白酶和逆转录酶基因片段的病毒测试载体，测量单个周期内的病毒复制。在191名新近感染的患者中，PolRC的变异范围很广，只有6%的变异是由耐药突变解释的。在联合抗逆转录病毒治疗前和治疗期间，感染POLRC低(小于或等于参考病毒的43%)的患者在研究开始时，无论是在联合抗逆转录病毒治疗前还是在联合抗逆转录病毒治疗期间，患者的CD4(+)T细胞计数显著增加，与耐药性和血浆HIV-1RNA水平无关。病毒PolRC可能通过影响病毒的复制量和组织分布来影响HIV-1的疾病进展。PolRC值43%可能代表了一个阈值，低于这个阈值，HIV-1已经降低了毒力，更不能耗尽CD4(+)T细胞计数。
Background. Infection with primary drug-resistant human immunodeficiency virus type 1 (HIV-1) has been associated with higher CD4(+) T cell counts in drug-naive patients, suggesting that altered viral pol replication capacity ( RC) associated with drug resistance diminishes immune injury in vivo, independent of exposure to drugs.Methods. Virus replication over a single cycle was measured by use of a viral test vector containing patient-derived HIV-1 protease and reverse transcriptase gene segments.Results. Among 191 recently infected patients, pol RC ranged widely, with only 6% of the variance explained by drug-resistance mutations. Patients infected with a virus with a low pol RC (less than or equal to43% of the reference virus) had significantly higher CD4(+) T cell counts at study entry, independent of drug resistance and plasma HIV-1 RNA level, and over time, both before and during combination antiretroviral therapy.Conclusions. Viral pol RC may influence HIV-1 disease progression by affecting the amount and tissue distribution of viral replication. The pol RC value of 43% may represent a threshold below which HIV-1 has lowered virulence and is less able to deplete CD4(+) T cell counts.