Division of Infectious Diseases and Ragon Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):229-35. doi: 10.1097/QAI.0b013e31823fd1f2.
Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication.
We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation.
Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation.
In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.
在接受有效抗逆转录病毒治疗(ART)的 HIV-1 感染患者中,关于持续病毒复制的程度仍存在争议。在低水平残留病毒血症患者中,在有效的 ART 基础上添加另一种有效的药物,如雷特格韦,可能会揭示是否存在持续的 HIV-1 复制。
我们之前报告了一项关于在 HIV-1 RNA <50 拷贝/毫升的接受 ART 的患者中强化使用雷特格韦的随机安慰剂对照研究的结果,该研究显示单拷贝检测法测量的残留病毒血症没有影响。我们现在报告了该试验中强化使用雷特格韦对其他潜在的持续 HIV-1 复制指标的影响,如下所示:2-LTR HIV-1 环、总细胞 HIV-1 DNA 和 T 细胞激活。
在 50 名接受检测的患者中,有 12 名(24%)在基线时有 2-LTR 环检测到。2-LTR 阳性的患者血浆 HIV-1 RNA 和 HIV-1 DNA 水平高于 2-LTR 阴性的个体。在强化使用雷特格韦治疗的第 12 周,2-LTR 环、总 HIV-1 DNA 或 2-LTR 环与总 HIV-1 DNA 的比值与基线相比均无变化。T 细胞激活标志物也没有变化。
在接受有效 ART 的 HIV-1 感染患者中,我们没有发现可被雷特格韦强化抑制的血液中持续病毒复制的证据。结果表明,仅强化使用雷特格韦不会根除 HIV-1 感染。