Efficient treatment and pre-exposure prophylaxis in rhesus macaques by an HIV fusion-inhibitory lipopeptide

Jing Xue; Huihui Chong; Yuanmei Zhu; Jingjing Zhang; Ling Tong; Jiahan Lu; Ting Chen; Zhe Cong; Qiang Wei; Yuxian He

doi:10.1016/j.cell.2021.11.032

Efficient treatment and pre-exposure prophylaxis in rhesus macaques by an HIV fusion-inhibitory lipopeptide

Cell. 2022 Jan 6;185(1):131-144.e18. doi: 10.1016/j.cell.2021.11.032. Epub 2021 Dec 16.

Authors

Jing Xue¹, Huihui Chong², Yuanmei Zhu², Jingjing Zhang³, Ling Tong³, Jiahan Lu³, Ting Chen³, Zhe Cong³, Qiang Wei⁴, Yuxian He⁵

Affiliations

¹ NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China; Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address: xuejing@cnilas.org.
² NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
³ NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China.
⁴ NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China; Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
⁵ NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address: yhe@ipb.pumc.edu.cn.

PMID: 34919814
DOI: 10.1016/j.cell.2021.11.032

Abstract

Two HIV fusion-inhibitory lipopeptides (LP-97 and LP-98) were designed with highly potent, long-acting antiviral activity. Monotherapy using a low dose of LP-98 sharply reduced viral loads and maintained long-term viral suppression in 21 SHIV_SF162P3-infected rhesus macaques. We found that five treated monkeys achieved potential posttreatment control (PTC) efficacy and had lower viral DNA in deep lymph nodes, whereas monkeys with a stable viral rebound had higher viral DNA in superficial lymph nodes. The tissues of PTC monkeys exhibited significantly decreased quantitative viral outgrowth and fewer PD-1⁺ central memory CD4⁺ T cells, and CD8⁺ T cells contributed to virologic control efficacy. Moreover, LP-98 administrated as a pre-exposure prophylaxis (PrEP) provided complete protection against SHIV_SF162P3 and SIVmac239 infections in 51 monkeys via intrarectal, intravaginal, or intravenous challenge. In conclusion, our lipopeptides exhibit high potential as an efficient HIV treatment or prevention strategy.

Keywords: CD8(+) T cells; HIV; PTC; PrEP; fusion inhibitor; lipopeptide; membrane fusion; posttreatment control; pre-exposure prophylaxis; viral reservoir.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
Female
HEK293 Cells
HIV Fusion Inhibitors / administration & dosage*
Humans
Lipopeptides / administration & dosage*
Macaca mulatta
Male
Pre-Exposure Prophylaxis / methods*
Simian Acquired Immunodeficiency Syndrome / drug therapy*
Simian Acquired Immunodeficiency Syndrome / immunology
Simian Acquired Immunodeficiency Syndrome / prevention & control*
Simian Acquired Immunodeficiency Syndrome / virology
Simian Immunodeficiency Virus*
Sustained Virologic Response
U937 Cells
Viral Load / drug effects

Substances

HIV Fusion Inhibitors
Lipopeptides