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加纳基于非核苷(酸)逆转录酶抑制剂的一线抗逆转录病毒疗法的高水平耐药性;一项2017年的研究。

High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study.

作者信息

Parbie Prince Kofi, Abana Christopher Zaab-Yen, Kushitor Dennis, Asigbee Theodore Worlanyo, Ntim Nana Afia Asante, Addo-Tetebo Gifty, Ansong Maclean Richard Darko, Ofori Sampson Badu, Mizutani Taketoshi, Runtuwene Lucky Ronald, Nishizawa Masako, Ishikawa Koichi, Kiyono Hiroshi, Ampofo William Kwabena, Matano Tetsuro, Bonney Evelyn Yayra, Kikuchi Tadashi

机构信息

AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.

出版信息

Front Microbiol. 2022 Aug 25;13:973771. doi: 10.3389/fmicb.2022.973771. eCollection 2022.

Abstract

Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS "95-95-95" target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)-M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)-K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTI-based antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana.

摘要

扩大获得有效抗逆转录病毒疗法(ART)的机会是管理人类免疫缺陷病毒(HIV)感染的一项主要手段。然而,HIV耐药性水平的上升严重阻碍了ART在HIV感染者(PLWH)中取得预期成功,尤其是来自非洲的感染者。尽管加纳在实现联合国艾滋病规划署“95-95-95”目标方面取得了巨大进展,但大量接受ART的PLWH尚未实现病毒抑制。本研究调查了加纳初治以及接受一线治疗方案药物的经治PLWH中的耐药突变模式。在一项横断面研究中,于2017年9月至10月从加纳科福里杜瓦东部地区医院的HIV/AIDS诊所收集了HIV-1感染成年人(≥18岁)的血样。从血浆中分离出的病毒RNA进行了蛋白酶抑制剂(PI)、逆转录酶抑制剂(RTI)和整合酶链转移抑制剂(INSTI)的基因型耐药性检测。本研究共对95名(84名经治,11名初治)HIV-1感染参与者进行了采样。60%(50/84)的经治参与者病毒血症得到控制(病毒载量<1000拷贝/ml)。在95份患者样本中,分别有32份、34份和33份成功对蛋白酶、逆转录酶和整合酶区域进行了测序。检测到的主要HIV-1亚型为CRF02_AG(70%)和A3(10%)。仅在逆转录酶抑制剂中检测到主要的耐药相关突变。主要的耐药突变是针对核苷(酸)逆转录酶抑制剂(NRTI)-M184V/I和非核苷(酸)逆转录酶抑制剂(NNRTI)-K103N。在经治组中,分别在54%(15/28)和46%(13/28)的个体中检测到M184V/I和K103N。在6名初治个体中,两种突变各在33%(2/6)的个体中被检测到。在57%的经治个体和2名初治个体中检测到对NRTI和NNRTI的多类耐药。本研究报告了加纳PLWH对基于NNRTI的抗逆转录病毒疗法的高水平耐药。然而,未检测到主要的PI和INSTI相关突变是一个良好信号,表明世界卫生组织目前推荐的多替拉韦与NRTI主干联合用药作为加纳PLWH的一线治疗方案将产生最大益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c9/9459847/966cdef243ac/fmicb-13-973771-g001.jpg

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