Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection

Minh Ha Ngo, Joshua Pankrac, Ryan C Y Ho, Emmanuel Ndashimye, Rahul Pawa, Renata Ceccacci, Tsigereda Biru, Abayomi S Olabode, Katja Klein, Yue Li, Colin Kovacs, Robert Assad, Jeffrey M Jacobson, David H Canaday, Stephen Tomusange, Samiri Jamiru, Aggrey Anok, Taddeo Kityamuweesi, Paul Buule, Ronald M GaliwangoSteven J Reynolds, Thomas C Quinn, Andrew D Redd, Jessica L Prodger, Jamie F S Mann, Eric J Arts

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

To date, an affordable, effective treatment for an HIV-1 cure remains only a concept with most "latency reversal" agents (LRAs) lacking specificity for the latent HIV-1 reservoir and failing in early clinical trials. We assessed HIV-1 latency reversal using a multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living with HIV-1 (PLWH) in Uganda, US and Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5-20 years on stable cART, HLP could target CD4+ T cells harbouring latent HIV-1 reservoir resulting in 100-fold more HIV-1 release into culture supernatant than by common recall antigens, and 1000-fold more than by chemotherapeutic LRAs. HLP induced release of a divergent and replication-competent HIV-1 population from PLWH on cART. These findings suggest HLP provides a targeted approach to reactivate the majority of latent HIV-1 proviruses among individuals infected with HIV-1.

Original languageEnglish
Article number2327371
Pages (from-to)2327371
JournalEmerging Microbes and Infection
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.

Keywords

  • Humans
  • HIV Infections
  • HIV-1
  • Virus Latency
  • CD4-Positive T-Lymphocytes
  • Canada

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