Effect of the L74I Polymorphism on Fitness of Cabotegravir-Resistant Variants of Human Immunodeficiency Virus 1 Subtype A6

被引：7

作者：

Hu, Zixin ^{[1
,2
]}

Cordwell, Trevor ^{[1
,2
]}

Nguyen, Hieu ^{[1
,2
]}

Li, Jialin ^{[1
,2
]}

Jeffrey, Jerry L. ^{[3
]}

Kuritzkes, Daniel R. ^{[1
,2
]}

机构：

[1] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA

[2] Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA

[3] ViiV Healthcare, Res Triangle Pk, NC USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2023年 / 228卷 / 10期

关键词：

HIV drug resistance; cabotegravir; integrase strand-transfer inhibitors; viral fitness; viral replication capacity; NONNUCLEOSIDE REVERSE-TRANSCRIPTASE; MUTATION; RILPIVIRINE; INTEGRASE;

D O I：

10.1093/infdis/jiad291

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The presence of human immunodeficiency virus (HIV) 1 subtype A6, characterized by the L74I integrase (IN) polymorphism, is associated with confirmed virologic failure in clinical trials of long-acting cabotegravir and rilpivirine. We investigated the effect of L74I on replication capacity (RC) of recombinant viruses carrying this polymorphism in combination with various IN stand-transfer inhibitor resistance mutations. The presence of L74I conferred greater RC to recombinant viruses expressing HIV-1 A6 IN when present together with G118R, G140R, Q148H, and R263K; no significant difference in RC was observed for the Q148K or R mutants. These findings may explain, in part, the association of HIV-1 subtype A6 with virologic failure.

引用

页码：1352 / 1356

页数：5

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