HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART.
HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART.
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DOI：
10.1016/j.ebiom.2016.07.024
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发表时间：
2016-09
期刊：
影响因子：
11.1
通讯作者：
Robb, Merlin L.
中科院分区：
文献类型：
--
作者：
Ananworanich, Jintanat;Chomont, Nicolas;Eller, Leigh Ann;Kroon, Eugene;Tovanabutra, Sodsai;Bose, Meera;Nau, Martin;Fletcher, James L. K.;Tipsuk, Somporn;Vandergeeten, Claire;O'Connell, Robert J.;Pinyakorn, Suteeraporn;Michael, Nelson;Phanuphak, Nittaya;Robb, Merlin L.
HIV DNA是HIV持续存在的标志物，可预测HIV进展和缓解，但其在早期急性HIV感染（AHI）中的动力学尚不清楚。我们纵向测量了19名未经治疗和71名经治疗的AHI参与者外周血单个核细胞携带总HIV DNA和整合HIV DNA的频率，其中50名处于最早的Fiebig I/II（HIV IgM −）阶段，即感染≤ 2周。在没有抗逆转录病毒治疗（ART）的情况下，HIV DNA在入组后2周达到峰值，2周后达到设定点，此后几乎没有变化。在ART的前2周内，未治疗组和治疗组之间的HIV DNA值存在显著差异，并随时间推移而增加。ART在2周后将总HIV DNA水平降低了20倍，3年后降低了316倍。因此，非常早期的ART提供了显着降低携带HIV DNA的细胞频率的机会。HIV DNA设定点在急性HIV感染的早期建立。在没有抗逆转录病毒治疗的情况下，急性艾滋病毒感染者的外周血单核细胞中的总艾滋病毒DNA是接受治疗者的300倍，整合的艾滋病毒DNA是接受治疗者的100倍。早期抗逆转录病毒治疗提供了一个机会，以显着减少前病毒HIV DNA的负担，艾滋病毒是难以治愈的，因为它感染的长寿细胞在体内，也被称为“水库”。拥有一个小的艾滋病毒储存库可能有益于健康。我们发现，外周血细胞中的HIV DNA是HIV储库大小的标志物，在感染的前6周内建立了一个设定点水平，并且在没有HIV药物的情况下随着时间的推移几乎没有变化。然而，如果早期开始使用艾滋病毒药物，储存库的大小会迅速下降，比未经治疗的人低300倍。目前，显著降低艾滋病毒储存库规模的最有效方法是早期治疗。
HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM −) stage, that is ≤ 2 weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2 weeks after enrollment, reaching a set-point 2 weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2 weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2 weeks and 316-fold after 3 years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA. The HIV DNA set-point is established early in acute HIV infection. Over three years without antiretroviral therapy, persons with acute HIV infection have total HIV DNA in peripheral blood mononuclear cells that is 300-fold and integrated HIV DNA that is 100-fold higher than those on treatment. Early antiretroviral therapy provides an opportunity to markedly reduce proviral HIV DNA burden, HIV is difficult to cure because it infects long-lived cells in the body, also called “reservoirs”. Having a small HIV reservoir size may benefit health. We show that HIV DNA in peripheral blood cells, a marker of the HIV reservoir size, establishes a set-point level during the first 6 weeks of infection and changes little over time without HIV medications. However, if HIV medications are started early, the reservoir size declines rapidly, and is 300-fold lower than that seen in untreated persons. Currently the most effective way to significantly lower the HIV reservoir size is with very early treatment.
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HIV-1 DNA预测疾病进展和治疗后病毒学控制。
影响因子：
7.7
作者：
Williams JP;Hurst J;Stöhr W;Robinson N;Brown H;Fisher M;Kinloch S;Cooper D;Schechter M;Tambussi G;Fidler S;Carrington M;Babiker A;Weber J;Koelsch KK;Kelleher AD;Phillips RE;Frater J;SPARTACTrial Investigators
通讯作者：
SPARTACTrial Investigators
DOI：
10.1097/qai.0b013e318269c414
发表时间：
2012-12-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Groves KC;Bibby DF;Clark DA;Isaksen A;Deayton JR;Anderson J;Orkin C;Stagg AJ;McKnight A
通讯作者：
McKnight A
影响因子：
158.5
作者：
Robb, Merlin L.;Eller, Leigh A.;Michael, Nelson L.
通讯作者：
Michael, Nelson L.
影响因子：
39.2
作者：
Henrich TJ;Hanhauser E;Marty FM;Sirignano MN;Keating S;Lee TH;Robles YP;Davis BT;Li JZ;Heisey A;Hill AL;Busch MP;Armand P;Soiffer RJ;Altfeld M;Kuritzkes DR
通讯作者：
Kuritzkes DR
影响因子：
3.8
作者：
De Souza, Mark S.;Phanuphak, Nittaya;Ananworanich, Jintanat
通讯作者：
Ananworanich, Jintanat