Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Service of Infectious Diseases, Virgen del Rocío University Hospital, Seville, Lab. 211, Planta 2, Avd. Manuel Siurot s/n, 41013 Seville, Spain.
Antimicrob Agents Chemother. 2011 Oct;55(10):4664-9. doi: 10.1128/AAC.00753-11. Epub 2011 Aug 1.
The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response was considered positive if either a reduction of ≥1-log(10) HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels were determined by using patients' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4(+) T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response after short-term maraviroc exposure. Lower CD4(+) T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists should be an early treatment option before the expansion of CXCR4-tropic strains.
8 天马拉维若单药治疗后的病毒学应答可作为一种替代方法，用于确定是否应为 HIV 感染患者开 CCR5 拮抗剂。目前尚不清楚有多少符合条件的患者可以接受包含马拉维若的联合抗逆转录病毒治疗，这种治疗是基于这项临床检测结果。同样，需要确定与拮抗剂暴露后的病毒学应答相关的临床和免疫病毒学因素。90 例连续 HIV 感染患者接受了 8 天马拉维若单药治疗。如果 HIV RNA 拷贝/ml 降低≥1-log(10)或病毒载量不可检测（<40 HIV RNA 拷贝/ml），则认为病毒学应答阳性。通过使用患者的病毒分离物和指示细胞系（U87-CXCR4 和 U87-CCR5）的多轮感染，确定 CXCR4 和 CCR5 嗜性病毒水平。病毒学应答阳性的患者比例为 72.2%（初治患者和治疗前患者分别为 94.7%和 66.2%）。在 CD4+T 细胞计数较低的患者中，阳性反应率急剧下降。短期马拉维若暴露后的病毒学应答与 CXCR4 嗜性病毒水平是唯一独立相关的变量。较低的 CD4+T 细胞层与较高的 CXCR4 嗜性病毒水平相关。这些结果支持在 CXCR4 嗜性株扩增之前，CCR5 拮抗剂应作为早期治疗选择的建议。
