Dinoso J B, Kim S Y, Wiegand A M, Palmer S E, Gange S J, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney M F, Proschan M A, Mican J M, Rehm C A, Coffin J M, Mellors J W, Siliciano R F, Maldarelli F
Departmentsof Medicine and Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9403-8. doi: 10.1073/pnas.0903107106. Epub 2009 May 22.
In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.
在接受目前推荐的抗逆转录病毒疗法（ART）的HIV-1感染者中，病毒血症降至每毫升<50拷贝的HIV-1 RNA，但大多数感染者一生中似乎都存在低水平的残余病毒血症。残余病毒血症是否源于持续的病毒复制周期存在争议。为了解决这个问题，我们进行了两项前瞻性研究，以评估在9名接受成功ART治疗的HIV-1感染者中，加用一种强效药物强化ART对残余病毒血症的影响。通过使用具有单拷贝灵敏度的HIV-1 RNA检测方法，我们发现，使用三种不同抗逆转录病毒药物（依非韦伦、洛匹那韦/利托那韦或阿扎那韦/利托那韦）中的任何一种强化ART，病毒血症水平均未降低。无反应与耐药病毒的存在或药物浓度不理想无关。我们的结果表明，残余病毒血症不是持续、完整的病毒复制周期的产物，而是来自稳定感染储存库的病毒输出。
