治疗前病毒载量对现代一线高效抗逆转录病毒治疗病毒学反应的影响。

Impact of pre-therapy viral load on virological response to modern first-line HAART.

作者信息

Santoro Maria Mercedes, Armenia Daniele, Alteri Claudia, Flandre Philippe, Calcagno Andrea, Santoro Mario, Gori Caterina, Fabeni Lavinia, Bellagamba Rita, Borghi Vanni, Forbici Federica, Latini Alessandra, Palamara Guido, Libertone Raffaella, Tozzi Valerio, Boumis Evangelo, Tommasi Chiara, Pinnetti Carmela, Ammassari Adriana, Nicastri Emanuele, Buonomini Annarita, Svicher Valentina, Andreoni Massimo, Narciso Pasquale, Mussini Cristina, Antinori Andrea, Ceccherini-Silberstein Francesca, Di Perri Giovanni, Perno Carlo Federico

机构信息

University of Rome Tor Vergata, Rome, Italy.

出版信息

Antivir Ther. 2013;18(7):867-76. doi: 10.3851/IMP2531. Epub 2013 Jan 23.

DOI:10.3851/IMP2531

PMID:23343501

Abstract

BACKGROUND

We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern first-line therapies.

METHODS

A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006-2009) were grouped according to levels of pre-HAART viraemia (≤ 30,000, 30,001-100,000, 100,001-300,000, 300,001-500,000 and > 500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤ 50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values > 50 copies/ml after virological success) were evaluated by Kaplan-Meier curves and Cox regression analyses.

RESULTS

Median pre-HAART viraemia was 5.1 log10 copies/ml (IQR 4.5-5.5), and 53% of patients had viraemia > 100,000 copies/ml. By week 48, the prevalence of patients reaching virological success was > 90% in all pre-HAART viraemia ranges, with the only exception of range > 500,000 copies/ml (virological success = 83%; P < 0.001). Higher pre-HAART viraemia was tightly correlated with longer median time to achieve virological success. Cox multivariable estimates confirmed this result: patients with pre-HAART viraemia > 500,000 copies/ml showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4+ T-cell count, transmitted drug resistance, calendar year and third drug administered (adjusted hazard ratio [95% CI]: 0.27 [0.21, 0.35]; P < 0.001). Pre-HAART viraemia > 500,000 copies/ml was also associated with higher probability of virological rebound compared with patients belonging to lower viraemia strata at weeks 4, 12 and 24 (P = 0.050).

CONCLUSIONS

At the time of modern HAART, and even though an average > 90% of virological success, high pre-HAART viraemia remains an independent factor associated with delayed and decreased virological success. Patients starting HAART with > 500,000 copies/ml represent a significant population that may deserve special attention.

摘要

背景

我们测试了在开始现代一线治疗的HIV-1感染患者中，HAART治疗前的病毒血症是否会影响病毒学成功的实现和维持。

方法

将2008年（中位数；四分位间距：2006 - 2009年）开始首次HAART（根据基因型定制）的1430例患者，按照HAART治疗前病毒血症水平（≤30,000、30,001 - 100,000、100,001 - 300,000、300,001 - 500,000和>500,000拷贝/毫升）进行分组。通过Kaplan-Meier曲线和Cox回归分析，评估治疗前病毒血症对达到病毒学成功（病毒血症≤50拷贝/毫升）的时间以及对病毒学反弹时间（病毒学成功后连续两次病毒血症值>50拷贝/毫升中的首次）的影响。

结果

HAART治疗前病毒血症的中位数为5.1 log10拷贝/毫升（四分位间距4.5 - 5.5），53%的患者病毒血症>100,000拷贝/毫升。到第48周时，在所有HAART治疗前病毒血症范围内，达到病毒学成功的患者患病率均>90%，唯一例外的是病毒血症>500,000拷贝/毫升的范围（病毒学成功 = 83%；P < 0.001）。较高的HAART治疗前病毒血症与达到病毒学成功的中位时间较长密切相关。Cox多变量估计证实了这一结果：在调整年龄、性别、HAART治疗前CD4 + T细胞计数、传播的耐药性、日历年和使用的第三种药物后，HAART治疗前病毒血症>500,000拷贝/毫升的患者显示出病毒学不可检测的最低风险（调整后的风险比[95%置信区间]：0.27 [0.21, 0.35]；P < 0.001）。与病毒血症较低分层的患者相比，在第4、12和24周时，HAART治疗前病毒血症>500,000拷贝/毫升的患者病毒学反弹的可能性也更高（P = 0.050）。