Post-treatment control of HIV infection

被引:151
作者
Conway, Jessica M. [1 ,2 ]
Perelson, Alan S. [2 ]
机构
[1] Penn State Univ, Dept Math, University Pk, PA 16802 USA
[2] Los Alamos Natl Lab, Theoret Biol & Biophys, Los Alamos, NM 87545 USA
基金
美国国家卫生研究院;
关键词
HIV latency; immune exhaustion; HIV viral rebound; mathematical modeling; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; LATENT RESERVOIR; HIV-1-INFECTED PATIENTS; VIRAL REPLICATION; LIFE-SPAN; IN-VIVO; VIREMIA; DYNAMICS; DECAY;
D O I
10.1073/pnas.1419162112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infected cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. Using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for noncontrollers consistent with observations.
引用
收藏
页码:5467 / 5472
页数:6
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