评价在临床环境中开始使用一线基于整合酶抑制剂的方案的 HIV-1 感染患者的病毒学应答和耐药情况。

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings.

机构信息

Saint Camillus International University of Health and Medical Sciences, Rome, Italy.

Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.

出版信息

J Clin Virol. 2020 Sep;130:104534. doi: 10.1016/j.jcv.2020.104534. Epub 2020 Jul 11.

DOI:10.1016/j.jcv.2020.104534

PMID:32769022

Abstract

BACKGROUND

Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting.

STUDY DESIGN

Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure.

RESULTS

Among 798 patients analysed, 38.6 %, 27.1 % and 34.3 % received raltegravir, elvitegravir and dolutegravir, respectively. Baseline resistance to NRTIs, NNRTIs, PIs and INIs was: 3.9 %, 13.9 %, 1.6 % and 0.5 %, respectively. Overall, by 12 months of treatment, the probability of VS was 95 %, while the probability of VR by 36 months after VS was 13.1 %. No significant differences in the virological response were found according to the INI used. The higher pre-therapy viremia strata was (<100,000 vs. 100,000-500,000 vs. > 500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P < 0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count <200 cell/mm was associated with the lowest probability of VS (91.5 %, P < 0.001) and the highest probability of VR (20.7 %, P = 0.008) compared to higher CD4 levels. Multivariable Cox-regression confirmed the negative role of high pre-therapy viremia and low CD4 cell count on VS, but not on VR. Forty-three (5.3 %) patients experienced VF (raltegravir: 30; elvitegravir: 9; dolutegravir: 4). Patients failing dolutegravir did not harbor any resistance mutation either in integrase or reverse transcriptase.

CONCLUSIONS

Our findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice.

摘要

背景

在临床环境中，对开始使用一线整合酶抑制剂（INIs）方案的初治患者进行了病毒学应答和耐药情况评估。

研究设计

通过生存分析评估治疗开始后的病毒学应答（VS）和病毒学反弹（VR）。在基线和病毒学失败时评估耐药性。

结果

在 798 名分析患者中，分别有 38.6%、27.1%和 34.3%接受了拉替拉韦、艾维雷韦和多替拉韦。基线时对 NRTIs、NNRTIs、PI 和 INIs 的耐药率分别为 3.9%、13.9%、1.6%和 0.5%。总体而言，治疗 12 个月时，VS 的概率为 95%，而 VS 后 36 个月时 VR 的概率为 13.1%。根据使用的 INI，病毒学反应无显著差异。较高的治疗前病毒载量（<100,000 vs. 100,000-500,000 vs. >500,000 拷贝/ml），VS 的概率越低（96.0% vs. 95.2% vs. 91.1%，均 P<0.001），VR 的概率越高（10.2% vs. 15.8% vs. 16.6%，均 P=0.010）。CD4 细胞计数<200 个/mm 与 VS 的最低概率（91.5%，P<0.001）和 VR 的最高概率（20.7%，P=0.008）相关，而与较高的 CD4 水平相关。多变量 Cox 回归证实了高治疗前病毒载量和低 CD4 细胞计数对 VS 的负作用，但对 VR 无影响。43 名（5.3%）患者出现病毒学失败（拉替拉韦：30 例；艾维雷韦：9 例；多替拉韦：4 例）。失败的多替拉韦患者在整合酶或逆转录酶中均未发现任何耐药突变。