Neutralizing antibodies associated with viremia control in a subset of individuals after treatment of acute human immunodeficiency virus type 1 infection
Neutralizing antibodies associated with viremia control in a subset of individuals after treatment of acute human immunodeficiency virus type 1 infection
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DOI：
10.1128/jvi.75.21.10200-10207.2001
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发表时间：
2001-11-01
影响因子：
5.4
通讯作者：
Rosenberg, ES
中科院分区：
文献类型：
--
作者：
Montefiori, DC;Hill, TS;Rosenberg, ES
急性人类免疫缺陷病毒1型（HIV-1）感染的立即治疗与治疗停止后病毒血症的后续控制有关，但有助于控制的免疫反应尚未完全确定。在这里，我们研究了中和抗体作为HIV-1感染者治疗中断后病毒血症控制的相关性，这些HIV-1感染者在早期血清转换期间开始了高活性抗逆转录病毒治疗（HAART），并持续治疗1至3年。治疗中断后立即，中和抗体检测不到T细胞系适应，菌株和自体的主要HIV-1分离的9名受试者中的7名。此时，通过酶联免疫吸附试验测定的Env和Gag特异性抗体也较低或不可检测。尽管在HAART期间病毒特异性B细胞应答明显不成熟，但自体中和抗体迅速出现，并与3例受试者治疗中断后反弹病毒血症的自发下调相关。在其他受试者中，在没有可检测到的中和抗体的情况下，观察到反弹病毒血症得到控制。结果表明，尽管HAART的早期机构，病毒特异性B细胞引发发生，允许快速二次中和抗体生产治疗中断后，在一个子集的个人。由于早期HAART限制了病毒的多样化，我们推测，对自体病毒的有效中和抗体反应能够成熟，并且在某些人中，这些反应有助于治疗停止后控制血浆病毒血症。
Immediate treatment of acute human immunodeficiency virus type 1 (HIV-1) infection has been associated with subsequent control of viremia in a subset of patients after therapy cessation, but the immune responses contributing to control have not been fully defined. Here we examined neutralizing antibodies as a correlate of viremia control following treatment interruption in HIV-1-infected individuals in whom highly active antiretriviral therapy (HAART) was initiated during early seroconversion and who remained on therapy for 1 to 3 years. Immediately following treatment interruption, neutralizing antibodies were undetectable with T-cell-line adapted, strains and the autologous primary HIV-1 isolate in seven of nine subjects. Env- and Gag-specific antibodies as measured by enzyme-linked immunosorbent assay were also low or undetectable at this time. Despite this apparent poor maturation of the virus-specific B-cell response during HAART, autologous neutralizing antibodies emerged rapidly and correlated with a spontaneous downregulation in rebound viremia following treatment interruption in three subjects. Control of rebound viremia was seen in other subjects in the absence of detectable neutralizing antibodies. The results indicate that virus-specific B-cell priming occurs despite the early institution of HAART, allowing rapid secondary neutralizing-antibody production following treatment interruption in a subset of individuals. Since early HAART limits viral diversification, we hypothesize that potent neutralizing-antibody responses to autologous virus are able to mature and that in some persons these responses contribute to the control of plasma viremia after treatment cessation.