Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection
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 par...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2327371 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850111865028345856 |
|---|---|
| author | 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. Galiwango Steven J. Reynolds Thomas C. Quinn Andrew D. Redd Jessica L. Prodger Jamie F. S. Mann Eric J. Arts |
| author_facet | 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. Galiwango Steven J. Reynolds Thomas C. Quinn Andrew D. Redd Jessica L. Prodger Jamie F. S. Mann Eric J. Arts |
| author_sort | Minh Ha Ngo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c4e48e2d64a24cd4aecbe0e0f13130b6 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-c4e48e2d64a24cd4aecbe0e0f13130b62025-08-20T02:37:32ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2327371Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infectionMinh Ha Ngo0Joshua Pankrac1Ryan C. Y. Ho2Emmanuel Ndashimye3Rahul Pawa4Renata Ceccacci5Tsigereda Biru6Abayomi S. Olabode7Katja Klein8Yue Li9Colin Kovacs10Robert Assad11Jeffrey M. Jacobson12David H. Canaday13Stephen Tomusange14Samiri Jamiru15Aggrey Anok16Taddeo Kityamuweesi17Paul Buule18Ronald M. Galiwango19Steven J. Reynolds20Thomas C. Quinn21Andrew D. Redd22Jessica L. Prodger23Jamie F. S. Mann24Eric J. Arts25Department of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaMaple Leaf Medical Clinic and Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, CanadaSpecial Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USASpecial Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USASpecial Immunology Unit and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USARakai Health Sciences Program, Kalisizo, UgandaRakai Health Sciences Program, Kalisizo, UgandaRakai Health Sciences Program, Kalisizo, UgandaRakai Health Sciences Program, Kalisizo, UgandaRakai Health Sciences Program, Kalisizo, UgandaRakai Health Sciences Program, Kalisizo, UgandaRakai Health Sciences Program, Kalisizo, UgandaDivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaDepartment of Microbiology and Immunology, University of Western Ontario, London, CanadaTo 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.https://www.tandfonline.com/doi/10.1080/22221751.2024.2327371HIV-1 latency reversallatency reversal agentvirus-like particlesCD4+ T cellschronic HIV-1 infectionreplication-competent latent reservoir |
| spellingShingle | 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. Galiwango Steven J. Reynolds Thomas C. Quinn Andrew D. Redd Jessica L. Prodger Jamie F. S. Mann Eric J. Arts Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection Emerging Microbes and Infections HIV-1 latency reversal latency reversal agent virus-like particles CD4+ T cells chronic HIV-1 infection replication-competent latent reservoir |
| title | Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection |
| title_full | Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection |
| title_fullStr | Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection |
| title_full_unstemmed | Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection |
| title_short | Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection |
| title_sort | effective and targeted latency reversal in cd4 t cells from individuals on long term combined antiretroviral therapy initiated during chronic hiv 1 infection |
| topic | HIV-1 latency reversal latency reversal agent virus-like particles CD4+ T cells chronic HIV-1 infection replication-competent latent reservoir |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2327371 |
| work_keys_str_mv | AT minhhango effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT joshuapankrac effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT ryancyho effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT emmanuelndashimye effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT rahulpawa effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT renataceccacci effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT tsigeredabiru effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT abayomisolabode effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT katjaklein effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT yueli effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT colinkovacs effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT robertassad effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT jeffreymjacobson effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT davidhcanaday effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT stephentomusange effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT samirijamiru effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT aggreyanok effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT taddeokityamuweesi effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT paulbuule effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT ronaldmgaliwango effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT stevenjreynolds effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT thomascquinn effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT andrewdredd effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT jessicalprodger effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT jamiefsmann effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection AT ericjarts effectiveandtargetedlatencyreversalincd4tcellsfromindividualsonlongtermcombinedantiretroviraltherapyinitiatedduringchronichiv1infection |