Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
J Antimicrob Chemother. 2012 Jun;67(6):1479-85. doi: 10.1093/jac/dks055. Epub 2012 Feb 23.
To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA of patients during maraviroc-based therapy.
Fourteen heavily high active antiretroviral therapy (HAART)-treated patients with a CCR5 Trofile profile were monitored over a 24 month period from the start of maraviroc therapy. Whole-blood samples were obtained at different timepoints, and coreceptor tropism was determined for proviral DNA from the V3-loop region sequence using the Geno2Pheno algorithm [false positive rate (FPR): 20%].
At the start of maraviroc treatment, 13/14 patients were viraemic (median: 4.33 log copies/mL). Concordance in R5 tropism (R5/R5) was observed between circulating HIV-RNA (Trofile) and HIV-DNA provirus in 10/14 patients (median FPR = 54.0%), while 4 patients showed a CXCR4-tropic R5/X4 variant in their provirus (FPR: 5.8%, 5.7%, 16.6% and 1.1%, respectively). All R5/R5 patients showed a stable HIV-1 DNA coreceptor usage. Two out of four R5/X4 patients showed a tropism shift in their archived provirus and, after 6 months a prevalence of R5-tropic virus was detected in DNA. The other two R5/X4 patients harboured the 11/25 genotype, and maintained X4 tropism in provirus during the study. Virological response did not reveal differences in RNA decay and CD4+ cell recovery in patients with discordant tropism.
A relatively good correlation between RNA and DNA tropism was observed at baseline. Proviral DNA tropism remained stable over 24 months of maraviroc-based therapy, indicating that determination of proviral DNA V3 sequence could be used in tropism prediction in clinical practice. The data also confirm the importance of the 11/25 rule in predicting viral tropism.
评估马拉维若治疗期间前病毒 DNA 中 HIV-1 核心受体嗜性的演变。
14 例接受高效抗逆转录病毒治疗（HAART）的重度患者，在开始接受马拉维若治疗后的 24 个月内进行监测。在不同时间点采集全血样本，使用 Geno2Pheno 算法（假阳性率（FPR）：20%）从 V3 环区序列确定前病毒 DNA 的核心受体嗜性。
在开始马拉维若治疗时，14 例患者中有 13 例病毒血症（中位数：4.33 log 拷贝/ml）。在 14 例患者中，10 例患者（中位数 FPR = 54.0%）在循环 HIV-RNA（Trofile）和 HIV-DNA 前病毒之间观察到 R5 嗜性（R5/R5）一致，而 4 例患者在其前病毒中显示出 CXCR4 嗜性的 R5/X4 变体（FPR：分别为 5.8%、5.7%、16.6%和 1.1%）。所有 R5/R5 患者均显示出稳定的 HIV-1 DNA 核心受体使用。4 例 R5/X4 患者中有 2 例在其存档前病毒中出现嗜性转变，6 个月后在 DNA 中检测到 R5 嗜性病毒的流行。另外 2 例 R5/X4 患者携带 11/25 基因型，并且在研究期间在前病毒中维持 X4 嗜性。病毒学反应并未显示在具有不同嗜性的患者中 RNA 衰减和 CD4+细胞恢复方面存在差异。
在基线时观察到 RNA 和 DNA 嗜性之间存在相对较好的相关性。在马拉维若治疗的 24 个月中，前病毒 DNA 嗜性保持稳定，表明在临床实践中可以使用前病毒 DNA V3 序列来预测嗜性。该数据还证实了 11/25 规则在预测病毒嗜性方面的重要性。
