马拉维若治疗免疫反应低下的 HIV-1 阳性患者的强化策略：一项意大利的随机临床试验。

Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial.

机构信息

Divisione Clinicizzata di Malattie Infettive, DIBIC "Luigi Sacco", Università degli Studi, Milano, Italy.

出版信息

PLoS One. 2013 Nov 14;8(11):e80157. doi: 10.1371/journal.pone.0080157. eCollection 2013.

BACKGROUND

Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs.

METHODS

We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+<200/µL and/or CD4+ recovery ≤ 25% and HIV-RNA<50 cp/mL. Patients were randomized 1:1 to HAART+maraviroc or continued HAART. CD4+ and CD8+ CD45+RA/RO, Ki67 expression and plasma IL-7 were quantified at W0, W12 and W48.

RESULTS

By W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/µL and CD4>200/µL + CD4 gain ≥ 25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=.01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48.

CONCLUSIONS

Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations.

TRIAL REGISTRATION

ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858.

背景

免疫无应答者（INRs）尽管接受高效抗逆转录病毒治疗（HAART）后病毒载量得到抑制，但 CD4 仍无增加，并且疾病进展的风险增加。我们评估了强化马拉维若治疗 INR 时的免疫重建情况。

方法

我们设计了一项多中心、随机、平行、开放标签、四期优效性试验。我们招募了 97 名 CD4+<200/µL 和/或 CD4+恢复≤25%和 HIV-RNA<50 cp/mL 的接受 HAART 的患者。患者按 1:1 随机分为 HAART+马拉维若组或继续 HAART 组。在 W0、W12 和 W48 时，定量检测 CD4+和 CD8+CD45+RA/RO、Ki67 表达和血浆 IL-7。

结果

到 W48 时，两组均显示 CD4 增加，但两组间无显著差异。与 HAART 组相比，HAART+马拉维若组在 W12（p=.009）和 W48（p=.025）时 CD8 有统计学意义的变化更有利。在 W12 时（p=.24 和 p=.619）和 W48 时（p=.076 和 p=.236），未达到 CD4>200/µL 和 CD4>200/µL+CD4 增加≥25%的终点。继续接受 HAART 的患者在 T 细胞稳态和激活的参数方面没有发生重大变化。接受马拉维若治疗的患者在 W48 时循环 IL-7 显著升高（p=.01），并且在 W12 时 HLA-DR+CD38+CD4+活化暂时减少（p=.06），但在 W48 时未维持。