Laboratory of Immunovirology, Biomedicine Institute of Seville, Service of Infectious Diseases, Virgen del Rocío University Hospital (IBiS/CSIC/SAS/University of Seville), Seville, Spain.
Antimicrob Agents Chemother. 2012 Nov;56(11):5858-64. doi: 10.1128/AAC.01406-12. Epub 2012 Sep 4.
The potential effect of blocking the CCR5 receptor on HIV disease progression biomarkers is not well understood. We showed that an 8-day maraviroc (MVC) monotherapy clinical test (MCT) can be used in selecting patients to receive MVC-containing combined antiretroviral therapy (cART). Using this MCT model, we assessed the effect of MVC on several HIV disease progression biomarkers during the MCT (MVC-specific effect) and following short-term (12-week) cART. We compared 45 patients on MVC monotherapy with a control group of 25 patients on MVC-sparing cART. We found that MVC did not modify any biomarkers in patients that had no virological response after the MCT. MVC-specific effects in patients with virological responses included increased CD8(+) T-cell activation and senescence levels, preservation of an increase in soluble CD14 (sCD14), and a decrease in D dimer levels. After 12 weeks, MVC-containing cART increased CD8(+) T-cell counts and preserved CD4(+) T-cell senescence levels compared with MVC-sparing cART. Moreover, there was a decrease in sCD14 levels in patients that received MVC-containing cART. In conclusion, effects compatible with CD8(+) T-cell redistribution in peripheral blood were observed after MVC therapy. However, MVC was associated with a favorable profile in HIV disease progression biomarkers only in patients with a virological response. These results support a potential clinical benefit of a therapy which includes MVC in HIV-infected patients.
阻断 CCR5 受体对 HIV 疾病进展生物标志物的潜在影响尚不清楚。我们表明,为期 8 天的马拉维若(MVC)单药治疗临床试验(MCT)可用于选择接受含 MVC 的联合抗逆转录病毒治疗(cART)的患者。使用这种 MCT 模型,我们评估了 MVC 在 MCT 期间(MVC 特异性作用)和短期(12 周)cART 后对几种 HIV 疾病进展生物标志物的影响。我们将 45 名接受 MVC 单药治疗的患者与 25 名接受 MVC 节约型 cART 的对照组进行了比较。我们发现,在 MCT 后没有病毒学反应的患者中,MVC 没有改变任何生物标志物。具有病毒学反应的患者中 MVC 的特异性作用包括 CD8(+)T 细胞激活和衰老水平增加,可溶性 CD14(sCD14)增加得以维持,D 二聚体水平降低。12 周后,与 MVC 节约型 cART 相比,含 MVC 的 cART 增加了 CD8(+)T 细胞计数并维持了 CD4(+)T 细胞衰老水平。此外,接受含 MVC 的 cART 的患者 sCD14 水平下降。总之,在 MVC 治疗后观察到外周血中 CD8(+)T 细胞重新分布的作用。然而,MVC 仅在病毒学反应患者中与 HIV 疾病进展生物标志物的有利特征相关。这些结果支持在 HIV 感染患者中包含 MVC 的治疗具有潜在的临床益处。