Effect of the L74I Polymorphism on Fitness of Cabotegravir-Resistant Variants of Human Immunodeficiency Virus 1 Subtype A6-Reference-Cited by-同舟云学术

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

Published:2023-07-27 Issue:10 Volume:228 Page:1352-1356
ISSN:0022-1899
Container-title:The Journal of Infectious Diseases
language:en
Short-container-title:

Author:

Hu Zixin¹,Cordwell Trevor¹,Nguyen Hieu¹,Li Jialin¹,Jeffrey Jerry L²,Kuritzkes Daniel R¹

Affiliation:

1. Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts , USA

2. ViiV Healthcare, Research Triangle Park , North Carolina , USA

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Link

https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiad291/51099873/jiad291.pdf

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