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初治抗逆转录病毒治疗患者中孤立的非核苷类逆转录酶抑制剂相关传播耐药性对治疗的反应

Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance.

作者信息

Clutter Dana S, Fessel W Jeffrey, Rhee Soo-Yon, Hurley Leo B, Klein Daniel B, Ioannidis John P A, Silverberg Michael J, Shafer Robert W

机构信息

*Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA; †Department of Internal Medicine, Kaiser Permanente Northern California, San Francisco Medical Center, San Francisco, CA; ‡Division of Research, Kaiser Permanente Northern California, Oakland, CA; §Department of Infectious Diseases, Kaiser Permanente Northern California, San Leandro Medical Center, San Leandro, CA; ‖Stanford Prevention Research Center, Department of Medicine, and ¶Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA; and #Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA.

出版信息

J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):171-6. doi: 10.1097/QAI.0000000000000942.

Abstract

BACKGROUND

Nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance.

METHODS

We reviewed treatment outcomes in a cohort of HIV-1-infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression.

RESULTS

Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01).

CONCLUSIONS

Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered.

摘要

背景

非核苷类逆转录酶抑制剂(NNRTI)相关的传播耐药性(TDR)是最常见的TDR类型。几乎没有数据可指导对此类耐药患者抗逆转录病毒治疗(ART)的选择。

方法

我们回顾了2002年4月至2014年5月间开始接受ART的一组HIV-1感染且仅存在NNRTI TDR的患者的治疗结果。在实际治疗分析中,病毒学失败(VF)定义为在24周内未达到病毒检测不到水平、病毒学反弹或病毒血症期间更换治疗方案。在意向性治疗分析中,失败的定义更为宽泛,包括VF、失访以及病毒学抑制期间更换治疗方案。

结果

3245例患者中,131例(4.0%)仅存在NNRTI TDR;122例接受了标准治疗方案,包括2种核苷类逆转录酶抑制剂(NRTI)加一种增强型蛋白酶抑制剂(bPI;n = 54)、一种整合酶链转移抑制剂(INSTI;n = 52)或一种NNRTI(n = 16)。中位随访时间为100周。在实际治疗分析中,bPI组、INSTI组和NNRTI组患者的VF发生率分别为15%(n = 8)、2%(n = 1)和25%(n = 4)。在多变量回归分析中,与bPI相比,INSTI导致VF的风险有降低趋势(风险比:0.14;95%置信区间:0.02至1.1;P = 0.07)。在意向性治疗多变量回归分析中,INSTI导致治疗失败的风险低于bPI(风险比:0.38;95%置信区间:0.18至0.82;P = 0.01)。

结论

仅存在NNRTI TDR的患者使用INSTI和bPI时VF发生率较低。在VF分析中,INSTI不劣于bPI,但在考虑换药频率和失访情况时优于bPI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5789/4876573/40ecb96806dd/qai-72-171-g003.jpg

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