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初治和经治 HIV 感染者中 M184V/I 对多替拉韦的反应:中低收入国家的影响。

Dolutegravir response in antiretroviral therapy naïve and experienced patients with M184V/I: Impact in low-and middle-income settings.

机构信息

Department of Microbiology and Immunology, Western University, London, Canada; Joint Clinical Research Centre, Center for AIDS Research Uganda Laboratories, Kampala, Uganda.

Department of Microbiology and Immunology, Western University, London, Canada.

出版信息

Int J Infect Dis. 2021 Apr;105:298-303. doi: 10.1016/j.ijid.2021.03.018. Epub 2021 Mar 16.

Abstract

BACKGROUND

Dolutegravir (DTG) is now recommended to all HIV infected adults, adolescents, and children of right age by WHO. The low cost of $75 per year for generic DTG-based combination, has allowed 3.9 million people living with HIV (PLWH) in low and middle-income countries (LMICs) access to DTG. Lamivudine and emtricitabine associated M184V/I mutation is highly prevalent in PLWH and the majority of HIV infected individuals receiving DTG regimens may already be carrying M184V/I mutation.

DISCUSSION

Despite high prevalence of M184V/I in antiretroviral therapy (ART) experienced patients, DTG treatment outcomes will likely not be adversely affected by this mutation. The use of DTG in ART naïve has been largely characterised by rare emergence of resistance and virological failure. DTG-based regimens have to great extent been effective at maintaining viral suppression in treatment experienced PLWH carrying M184V/I.

CONCLUSIONS

Initiating patients on DTG may help preserve more treatment options for HIV infected individuals living in LMICs. High genetic barrier to the development of resistance associated with DTG and progressive viral suppression in patients switched to DTG-based therapy with M184V/I, may encourage better DTG outcomes and help in curbing increasing levels of HIV drug resistance in LMICs.

摘要

背景

世界卫生组织(WHO)建议所有 HIV 感染者、青少年和适龄儿童使用多替拉韦(DTG)。基于 DTG 的通用复方药物每年的费用低至 75 美元,这使得 390 万生活在中低收入国家(LMIC)的 HIV 感染者能够获得 DTG。拉米夫定和恩曲他滨相关的 M184V/I 突变在 HIV 感染者中非常普遍,而大多数接受 DTG 方案治疗的 HIV 感染者可能已经携带 M184V/I 突变。

讨论

尽管在接受过抗逆转录病毒治疗(ART)的患者中 M184V/I 的发生率很高,但 DTG 治疗结果可能不会受到这种突变的不利影响。在初治患者中使用 DTG 主要表现为耐药性罕见出现和病毒学失败。基于 DTG 的方案在治疗经验丰富的携带 M184V/I 的 HIV 感染者中,在维持病毒抑制方面非常有效。

结论

为患者启动 DTG 治疗可能有助于为生活在 LMIC 的 HIV 感染者保留更多的治疗选择。DTG 具有较高的耐药相关基因突变屏障,且在携带 M184V/I 的患者中转换为 DTG 治疗后病毒逐渐得到抑制,这可能会鼓励更好的 DTG 治疗结果,并有助于遏制 LMIC 中 HIV 耐药水平的不断上升。

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