Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors

被引：20

作者：

Hachiya, Atsuko ^{[1
,2
]}

Kirby, Karen A. ^{[3
]}

Ido, Yoko ^{[1
]}

Shigemi, Urara ^{[1
]}

Matsuda, Masakazu ^{[1
]}

Okazaki, Reiko ^{[1
]}

Imamura, Junji ^{[1
]}

Sarafianos, Stefan G. ^{[3
,4
]}

Yokomaku, Yoshiyuki ^{[1
]}

Iwatani, Yasumasa ^{[1
,5
]}

机构：

[1] Natl Hosp Org, Dept Infect Dis & Immunol, Clin Res Ctr, Nagoya Med Ctr, Nagoya, Aichi, Japan

[2] Natl Hosp Org, Div Biol Informat Anal, Clin Res Ctr, Nagoya Med Ctr, Nagoya, Aichi, Japan

[3] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Christopher S Bond Life Sci Ctr, Columbia, MO 65212 USA

[4] Univ Missouri, Dept Biochem, Columbia, MO USA

[5] Nagoya Univ, Dept AIDS Res, Grad Sch Med, Nagoya, Aichi, Japan

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2017年 / 61卷 / 08期

基金：

美国国家科学基金会;

关键词：

dolutegravir; drug resistance mechanisms; human immunodeficiency virus; integrase; integrase strand transfer inhibitor; RANDOMIZED CONTROLLED-TRIAL; VIRUS TYPE-1 INTEGRASE; ANTIRETROVIRAL ACTIVITY; LEVEL RESISTANCE; DRUG-RESISTANCE; R263K MUTATION; DOUBLE-BLIND; IN-VITRO; RALTEGRAVIR; DOLUTEGRAVIR;

D O I：

10.1128/AAC.00315-17

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A novel HIV-1 integrase mutation pattern, L74F V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153-and 197-fold, respectively). These findings are important for the development of an accurate system for interpretation of INSTI resistance and the rational design of next-generation INSTIs.

引用

页数：7

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