Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy

Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy
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DOI:
10.1001/jama.282.17.1627
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发表时间:
1999-11-03
影响因子:
120.7
通讯作者:
Pomerantz, RJ
Pomerantz, RJ
中科院分区:
医学1区
文献类型:
--
作者:
Dornadula, G;Zhang, H;Pomerantz, RJ

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尽管使用高效抗逆转录病毒疗法(HAART)进行抑制性治疗,目的探讨在接受抑制性HAART治疗的患者外周血单个核细胞和生殖器细胞中是否能检测到游离病毒RNA,研究设计:1998年11月至1999年5月进行的前瞻性队列研究。人类免疫缺陷病毒1型感染者(20名男性和2名女性)在我们的实验室中显示,当服用抑制性HAART时,外周血血浆中的HIV-1 RNA低于50拷贝/mL。使用超灵敏的逆转录聚合酶链反应定量,该反应能够将无细胞病毒体RNA定量至5拷贝/mL的下限,并定性检测低于该水平的病毒RNA。在外周血血浆中可以检测到残留的病毒RNA(平均水平,17拷贝/mL)。病毒RNA的存在表明正在进行的病毒复制正在发生,尽管在每名患者中的水平较低,与血浆相比,大多数患者生殖器液中的病毒RNA水平较低,12例患者检测不到病毒RNA。1在服用抑制性HAART的患者中,不仅可以在外周血单核细胞中,而且可以在外周血浆中以无细胞病毒体RNA的形式被证明。完全消除病毒复制可能需要加强抗逆转录病毒治疗,而不是标准的抑制性HAART。
Context Despite suppressive treatment with highly active antiretroviral therapy (HAART), replication-competent virus can still be isolated from peripheral blood mononuclear cells and genital cells of many individuals receiving suppressive HAART.Objective To determine whether free virion RNA can be detected in the blood plasma and/or genital tract fluids from patients receiving suppressive HAART.Design Prospective cohort study conducted from November 1998 to May 1999.Setting Academic medical center.Patients Human immunodeficiency virus 1-infected individuals (20 men and 2 women) shown in our laboratories to have fewer than 50 copies/mL of HIV-1 RNA in peripheral blood plasma while taking suppressive HAART.Main Outcome Measures Free virion RNA levels in peripheral blood plasma and genital fluids, quantified using an ultrasensitive reverse transcriptase polymerase chain reaction able to quantify cell-free virion RNA to a lower limit of 5 copies/mL and qualitatively detect viral RNA below this level.Results In all 22 patients, residual viral RNA could be detected in the peripheral blood plasma (mean level, 17 copies/mL). The presence of viral RNA suggests that ongoing viral replication is occurring, albeit at low levels, in each patient evaluated, Viral RNA levels were lower in most patients' genital fluids compared with blood plasma and in 12 patients were undetectable.Conclusions These data suggest that low-level replication of HIV-1 in patients taking suppressive HAART may be demonstrated not only in peripheral blood mononuclear cells but also in peripheral plasma as cell-free virion RNA. Complete ablation of viral replication may require intensification of antiretroviral therapies beyond standard suppressive HAART.