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含多替拉韦(DTG)方案治疗接受拉替拉韦(RAL)或艾维雷韦(EVG)后的病毒学反弹:意大利大型 HIV 耐药性网络(ARCA)中的持久性和病毒学应答。

Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): Durability and virological response in a large Italian HIV drug resistance network (ARCA).

机构信息

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

ITB-CNR, Segrate, MI, Italy.

出版信息

J Clin Virol. 2018 Aug;105:112-117. doi: 10.1016/j.jcv.2018.06.012. Epub 2018 Jun 21.

DOI:10.1016/j.jcv.2018.06.012
PMID:29957545
Abstract

BACKGROUND

Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens.

OBJECTIVES

We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response.

STUDY DESIGN

From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression.

RESULTS

After a median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced ≥10 regimens (HR 0.11, p = 0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p < .001) and significantly decreased in patients with CD4 nadir >200/μL (HR 0.29, p = 0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start.

CONCLUSIONS

After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.

摘要

背景

多替拉韦(DTG)是一种下一代 HIV 整合酶抑制剂(INI),与拉替拉韦(RAL)或艾维雷韦(EVG)相比,其耐药的遗传屏障更高。关于含 DTG 方案的持久性的数据很少。

目的

我们旨在研究含 DTG 方案的持续时间、HIV-1 RNA 短暂回升的发生情况以及与 DTG 病毒学反应相关的因素。

研究设计

我们从抗病毒反应队列分析数据库中选择了 89 名接受过 RAL 或 EVG 治疗后开始接受 DTG 的四药经验 HIV-1 阳性患者。通过逻辑回归分析与持久性和病毒学反应相关的因素。

结果

在中位时间为 18.8 [0.4-76.2] 个月后,89/89(88.8%)名患者仍在接受 DTG 治疗。所有在随访结束时仍在接受 DTG 治疗的患者的 HIV-1 RNA 均无法检测到,而在 10 名停药的患者中,有 5 名无法检测到 HIV-1 RNA。在接受过≥10 种方案的患者中,DTG 停药的频率较低(HR 0.11,p=0.040)。在最后一次随访时 HIV-1 RNA 阳性值的发生概率在非 B 型 HIV-1 亚型的患者中显著增加(HR 5.77,p<0.001),在 CD4 最低点>200/μL 的患者中显著降低(HR 0.29,p=0.038),在接受过>10 种方案的患者中显著降低(HR 0.27,p=0.040),在开始 DTG 治疗时携带整合酶突变的病毒的患者中显著降低(HR 0.12,p=0.023)。

结论

在接受第一代 INIs 治疗后,DTG 治疗显示出较长的持久性,在病毒学抑制后没有出现病毒学反弹。感染非 B 型 HIV-1 亚型的患者在最后一次观察时 HIV-1 RNA 可检测的风险更大。

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