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替诺福韦(TDF)和达芦那韦/利托那韦(DRV/RTV)联合抗反转录病毒治疗 HIV-1 阳性患者:病例报告、文献综述和荟萃分析,探讨使用蛋白酶抑制剂联合 NRTI 的双重治疗策略。

Dual antiretroviral therapy with tenofovir (TDF) and darunavir/ritonavir (DRV/RTV) in an HIV-1 positive patient: a case report, review, and meta-analysis of the literature on dual treatment strategies using protease inhibitors in combination with an NRTI.

机构信息

Institute of Medical Microbiology, Jena University Hospital, Jena, Germany.

Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.

出版信息

Infection. 2018 Oct;46(5):599-605. doi: 10.1007/s15010-018-1171-z. Epub 2018 Jun 30.

DOI:10.1007/s15010-018-1171-z
PMID:29961209
Abstract

BACKGROUND

Here, we report the case of an HIV positive patient under a dual antiretroviral drug regimen with tenofovir disoproxil and darunavir/ritonavir with stable clinical, virological, and immunological response over 126 weeks. Dual antiretroviral therapy has the advantage of reduced toxicity and lower health care costs, treatment failure and fostering drug resistance are perceived risks. Optimal drug combinations and indication criteria for dual treatment remain controversial. Nevertheless, first clinical trials indicate non-inferiority for combinations of nucleoside reverse transcriptase inhibitors and protease inhibitors. This case presents the combination of tenofovir disoproxil in combination with a protease inhibitor as a new potential dual treatment regimen.

METHOD

We performed a systematic literature search and meta-analysis of trials comparing dual to triple ART.

RESULTS

Literature review revealed nine studies in which dual therapy with a protease inhibitor and an NRTI was compared to triple therapy. We performed a meta-analysis of six trials that reported a 48-week follow-up. In treatment-naïve patients as well when ART switch was assessed, there was no difference in the treatment success in patients with dual ART versus triple.

CONCLUSION

We conclude that dual therapy with a protease inhibitor and NRTI is safe and effective. The use of tenofovir in dual treatment as described in our case needs to be assessed in future clinical trials.

摘要

背景

在这里,我们报告了一例 HIV 阳性患者,该患者接受了替诺福韦二吡呋酯和达芦那韦/利托那韦的双重抗逆转录病毒药物治疗方案,在 126 周的时间内,临床、病毒学和免疫反应均稳定。双重抗逆转录病毒治疗具有降低毒性和降低医疗保健成本的优势,但治疗失败和耐药性被认为是存在风险的。最佳的药物组合和双重治疗的适应证标准仍存在争议。然而,首次临床试验表明,核苷逆转录酶抑制剂和蛋白酶抑制剂联合使用具有非劣效性。本病例报告了替诺福韦二吡呋酯与蛋白酶抑制剂联合使用作为一种新的潜在双重治疗方案。

方法

我们对比较双重与三联抗逆转录病毒治疗的临床试验进行了系统的文献检索和荟萃分析。

结果

文献复习共发现了九项比较蛋白酶抑制剂联合 NRTI 双重治疗与三联治疗的研究。我们对六项报告了 48 周随访的试验进行了荟萃分析。在治疗初治患者和评估 ART 转换时,双重 ART 组和三联治疗组的治疗成功率无差异。

结论

我们得出结论,蛋白酶抑制剂联合 NRTI 的双重治疗是安全有效的。在未来的临床试验中,需要评估替诺福韦在双重治疗中的应用。

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Dual antiretroviral therapy with tenofovir (TDF) and darunavir/ritonavir (DRV/RTV) in an HIV-1 positive patient: a case report, review, and meta-analysis of the literature on dual treatment strategies using protease inhibitors in combination with an NRTI.替诺福韦(TDF)和达芦那韦/利托那韦(DRV/RTV)联合抗反转录病毒治疗 HIV-1 阳性患者:病例报告、文献综述和荟萃分析,探讨使用蛋白酶抑制剂联合 NRTI 的双重治疗策略。
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本文引用的文献

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Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0.2017 年欧洲艾滋病临床学会(EACS)成人 HIV 阳性感染者治疗指南第 9.0 版要点。
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Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial.达芦那韦/利托那韦联合拉米夫定与达芦那韦/利托那韦联合替诺福韦酯/富马酸丙酚替诺福韦和恩曲他滨或阿巴卡韦/拉米夫定治疗维持人类免疫缺陷病毒 1 型病毒抑制的疗效比较:随机、开放标签、非劣效性 DUAL-GESIDA 8014-RIS-EST45 试验。
Clin Infect Dis. 2017 Nov 29;65(12):2112-2118. doi: 10.1093/cid/cix734.
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Lipid testing in infectious diseases: possible role in diagnosis and prognosis.感染性疾病中的脂质检测:在诊断和预后中的可能作用。
Infection. 2017 Oct;45(5):575-588. doi: 10.1007/s15010-017-1022-3. Epub 2017 May 8.
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Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL.在HIV-1 RNA≤50 cp/mL的HIV感染患者中换用达芦那韦/利托那韦联合拉替拉韦进行双重治疗的疗效和耐受性。
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Evolution of blood-associated HIV-1 DNA levels after 48 weeks of switching to atazanavir/ritonavir+lamivudine dual therapy versus continuing triple therapy in the randomized AtLaS-M trial.在 AtLaS-M 随机试验中,与继续三联治疗相比,换用阿扎那韦/利托那韦+拉米夫定双治疗 48 周后血液中 HIV-1 DNA 水平的演变。
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Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M).在病毒学抑制的HIV-1感染患者中,将治疗简化为阿扎那韦/利托那韦+拉米夫定与维持阿扎那韦/利托那韦+两种核苷类逆转录酶抑制剂的比较:一项随机试验(ATLAS-M)的48周结果
J Antimicrob Chemother. 2017 Apr 1;72(4):1163-1171. doi: 10.1093/jac/dkw557.
7
Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate.中等级别管状蛋白尿在 HIV 阳性患者中很常见,特别是与富马酸替诺福韦二吡呋酯的暴露有关。
Infection. 2016 Oct;44(5):641-9. doi: 10.1007/s15010-016-0911-1. Epub 2016 Jun 2.
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Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials.蛋白酶抑制剂单药治疗与三联疗法的疗效:对13项随机试验中2303例患者数据的荟萃分析。
HIV Med. 2016 May;17(5):358-67. doi: 10.1111/hiv.12348. Epub 2015 Dec 28.
9
HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial.艾滋病挽救治疗无需核苷类逆转录酶抑制剂:一项随机对照试验
Ann Intern Med. 2015 Dec 15;163(12):908-17. doi: 10.7326/M15-0949. Epub 2015 Nov 24.
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Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial.在 HIV-1 病毒学稳定的患者中,使用阿扎那韦-利托那韦联合拉米夫定进行双重治疗与使用阿扎那韦-利托那韦联合两种核苷(酸)逆转录酶抑制剂进行三重治疗的疗效比较(SALT):一项随机、开放标签、非劣效性试验的 48 周结果。
Lancet Infect Dis. 2015 Jul;15(7):775-84. doi: 10.1016/S1473-3099(15)00097-3. Epub 2015 Jun 7.