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格鲁吉亚初治失败的 HIV 感染者中 HIV 耐药性的流行病学研究。

Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.

机构信息

Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia.

Ivane Javakhishvili Tbilisi State University, Tbilisi, Georgia.

出版信息

J Med Virol. 2019 Feb;91(2):235-240. doi: 10.1002/jmv.25245. Epub 2018 Oct 17.

DOI:10.1002/jmv.25245
PMID:29905958
Abstract

Human immunodeficiency virus (HIV) drug resistance is a major threat to the sustained impact of antiretroviral therapy (ART). We studied the epidemiology of drug resistance in the country of Georgia. The study included all adult patients who experienced virologic failure on first line ART and received HIV drug resistance testing between 2005 and 2016. The Stanford HIV Sequence Database was used for interpretation of the resistance data. Patient-level data were extracted from the national AIDS health information system. Of the 447 patients included, 85.5% harbored the subtype A6 virus, 8.0% - subtype B, 2.9% - subtype G, and other subtypes were <1%. The most frequent first-line regimens were Tenofovir/Emtricitabine/Efavirenz (28.4%), Zidovudine/Lamivudine/Efavirenz (28.4%), and Abacavir/Lamivudine/Efavirenz (15.9%). A total of 85.0% of the patients with treatment failure developed at least one drug resistance mutation affecting their susceptibility to ART. The most frequent nucleoside reverse transcriptase inhibitor mutations were M184V (65.3%), K65R (19.7%) and L74V (17.0%). At least three thymidine analogue mutations were detected in 6.3% of the patients. From non-nucleoside reverse transcriptase inhibitor mutations, G190S was shown to be the most prevalent (49.4%), followed by K101E (27.10%) and K103N (24.4%). G190S and K101E were more common in subtype A as compared with non-A viruses (G190S: 54.9% vs 11.3%, P < 0.0001; K101E: 29.8% vs 11.3%, P = 0.005). On the other hand, K103N was more frequent in non-A subtypes (43.4%) compared with subtype A (22.2%), P = 0.0008. A majority of persons failing on ART had HIV drug resistance. Drug resistance patterns may vary by subtype. K65R mutation remains below 20%, but given the high use of Tenofovir in the country, continuing surveillance of drug resistance is needed.

摘要

人类免疫缺陷病毒(HIV)耐药性是抗逆转录病毒治疗(ART)持续产生效果的主要威胁。我们研究了格鲁吉亚的耐药性流行情况。该研究包括 2005 年至 2016 年间首次一线 ART 失败并接受 HIV 耐药性检测的所有成年患者。耐药数据的解释使用了斯坦福 HIV 序列数据库。从国家艾滋病健康信息系统中提取患者水平数据。447 例患者中,85.5%携带 A6 亚型病毒,8.0%为 B 亚型,2.9%为 G 亚型,其他亚型<1%。最常见的一线方案是替诺福韦/恩曲他滨/依非韦伦(28.4%)、齐多夫定/拉米夫定/依非韦伦(28.4%)和阿巴卡韦/拉米夫定/依非韦伦(15.9%)。85.0%的治疗失败患者出现至少一种影响其对 ART 敏感性的耐药性突变。最常见的核苷逆转录酶抑制剂突变是 M184V(65.3%)、K65R(19.7%)和 L74V(17.0%)。6.3%的患者至少检测到三种胸苷类似物突变。非核苷逆转录酶抑制剂突变中,G190S 最为常见(49.4%),其次是 K101E(27.10%)和 K103N(24.4%)。与非 A 病毒相比,A 亚型中 G190S 和 K101E 更为常见(G190S:54.9% vs 11.3%,P<0.0001;K101E:29.8% vs 11.3%,P=0.005)。另一方面,非 A 亚型中 K103N 更为常见(43.4%),而 A 亚型中 K103N 较少见(22.2%),P=0.0008。大多数接受 ART 治疗失败的人都有 HIV 耐药性。耐药模式可能因亚型而异。K65R 突变仍低于 20%,但鉴于该国大量使用替诺福韦,仍需继续监测耐药性。

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