Infectious Diseases Division 1st Internal Medicine Department, AHEPA University Hospital Thessaloniki, 54636 Thessaloniki, Greece.
Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, 26504 Patras, Greece.
Viruses. 2024 Aug 30;16(9):1392. doi: 10.3390/v16091392.
M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation (RAM) is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of the M184V mutation on the treatment outcomes in people living with HIV (PLWH). Since 3TC remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure (VF). ART guidelines do not recommend the use of drugs impacted by RAMs as they have been confirmed to comprise a risk factor for VF. However, there is evidence that 3TC/FTC can remain active even in the presence of M184V. Given the potential benefits of 3TC in ART combinations, the investigation of M184V remains of high interest to clinicians and researchers, especially in certain regions with limited resources, and especially for its unusual effects. This is a review of the literature on the challenges in treating both naïve and experienced individuals carrying the M184V mutation, including virological failure, virological suppression, and resistance to ART.
M184V 是逆转录酶（RT）的 YMDD 结构域中的单碱基突变。与拉米夫定（3TC）和恩曲他滨（FTC）的抗病毒无应答相关的 M184V 耐药相关突变（RAM），以及对这两种抗逆转录病毒药物产生高水平耐药。在非抑制性抗逆转录病毒治疗（ART）的情况下，M184V 迅速被选择，并在 HIV 储存库中积累。人们一直在努力评估 M184V 突变对 HIV 感染者（PLWH）治疗结果的影响。由于 3TC 仍然是推荐的抗逆转录病毒联合治疗中广泛使用的一部分，因此在病毒学失败（VF）的患者中通常可以检测到 M184V。ART 指南不建议使用受 RAM 影响的药物，因为它们已被证实是 VF 的一个风险因素。然而，有证据表明，即使存在 M184V，3TC/FTC 仍可能保持活性。鉴于 3TC 在 ART 联合治疗中的潜在益处，M184V 的研究仍然是临床医生和研究人员非常关注的问题，特别是在资源有限的某些地区，特别是因为其不寻常的影响。这是一篇对治疗携带 M184V 突变的初治和经验丰富的个体所面临挑战的文献综述，包括病毒学失败、病毒学抑制和对 ART 的耐药性。
