4.6 Review

New Latency Reversing Agents for HIV-1 Cure: Insights from Nonhuman Primate Models

Related references

Note: Only part of the references are listed.
Article Immunology

Vesatolimod, a Toll-like Receptor 7 Agonist, Induces Immune Activation in Virally Suppressed Adults Living With Human Immunodeficiency Virus-1

Sharon A. Riddler et al.

Summary: In a Phase Ib study investigating the effects of vesatolimod in adults with HIV-1, the drug was found to be generally well tolerated and immune stimulation was observed at doses above 4 mg, indicating potential for future combination trials in individuals living with HIV.

CLINICAL INFECTIOUS DISEASES (2021)

Article Virology

Simian-Human Immunodeficiency Virus SHIVCCH505 Persistence in ART-Suppressed Infant Macaques Is Characterized by Elevated SHIV RNA in the Gut and a High Abundance of Intact SHIV DNA in Naive CD4(+) T Cells

Veronica Obregon-Perko et al.

Summary: Mother-to-child transmission of HIV-1 through breastfeeding poses challenges for initiating early antiretroviral therapy (ART). A study using infant rhesus macaques infected with SHIV identified sites of viral persistence under ART, with the gastrointestinal tract being an active site of virus transcription. Naive CD4(+) T cells were found to harbor intact provirus and contribute significantly to the viral reservoir, providing insight into potential targets for cure strategies in pediatric populations.

JOURNAL OF VIROLOGY (2021)

Article Infectious Diseases

Latency Reversal 2.0: Giving the Immune System a Seat at the Table

Vidisha Singh et al.

Summary: While significant progress has been made in terms of virus reactivation from latency, the initial hope for virus eradication through latency reversal alone has not been realized. Effective latency reversal strategies will likely need to be combined with approaches that facilitate immune recognition and clearance of cells containing reactivated virus.

CURRENT HIV/AIDS REPORTS (2021)

Article Immunology

Impact of Anti-PD-1 and Anti-CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study

Thomas A. Rasmussen et al.

Summary: The study tested the combination of anti-PD-1 and anti-CTLA-4 therapy in HIV-infected individuals with cancer, finding that the combination therapy increased HIV RNA levels and potentially eliminated cells containing replication-competent HIV.

CLINICAL INFECTIOUS DISEASES (2021)

Article Virology

New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention, and Cure

Hui Li et al.

Summary: The study demonstrates the successful construction of SHIVs with bulky aromatic substitutions at residue 375, allowing efficient replication in rhesus macaques and effective transmission across rectal, vaginal, penile, oral, or intravenous routes. These SHIVs can serve as a model for HIV-1 infection studies in preclinical monkey trials.

JOURNAL OF VIROLOGY (2021)

Article Virology

CD8 Lymphocyte Depletion Enhances the Latency Reversal Activity of the SMAC Mimetic AZD5582 in ART-Suppressed Simian Immunodeficiency Virus-Infected Rhesus Macaques

Maud Mavigner et al.

Summary: The study demonstrated that inducing latency reversal using the SMAC mimetic/IAP inhibitor AZD5582, in combination with CD8 alpha cell depletion, can enhance viral latency reversal in SIV-infected rhesus macaques. All six animals treated with the combined therapy showed increased on-ART viremia, indicating a potential role of CD8(+) T cells in maintaining and inhibiting latency reversal during HIV/SIV infection.

JOURNAL OF VIROLOGY (2021)

Article Multidisciplinary Sciences

Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques

Anthony M. Cadena et al.

Summary: The viral DNA is widely distributed in multiple tissues, while viral RNA is mainly restricted to lymph nodes. Under long-term ART suppression, persistent viral RNA transcription mainly occurs in secondary lymphoid organs.

NATURE COMMUNICATIONS (2021)

Article Medicine, Research & Experimental

CD8+ T cells fail to limit SIV reactivation following ART withdrawal until after viral amplification

Afam A. Okoye et al.

Summary: The study found that CD8+ T cell depletion did not significantly affect the control of SIV reactivation during ART, but after ART cessation, rhesus macaques with CD8+ T cell depletion showed a significant increase in post-ART plasma viremia.

JOURNAL OF CLINICAL INVESTIGATION (2021)

Article Multidisciplinary Sciences

IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques

Justin Harper et al.

Summary: The study demonstrated that sequential interleukin-21 and interferon alpha therapy can generate terminally differentiated natural killer cells with potent activity in SIV-infected rhesus macaques, reducing SIV dissemination in lymph nodes. This suggests that the differentiation profiles of natural killer cells seen in African green monkeys can be rescued in rhesus macaques to promote viral clearance in tissues.

NATURE COMMUNICATIONS (2021)

Article Cell Biology

The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy

Devi SenGupta et al.

Summary: TLR7 agonist vesatolimod, when combined with ART, showed potential to delay viral rebound in HIV-1-infected controllers by reducing intact proviral DNA levels at the end of treatment. Further larger clinical studies are needed to evaluate the efficacy of vesatolimod-based combination therapies for long-term control of HIV infection.

SCIENCE TRANSLATIONAL MEDICINE (2021)

Article Multidisciplinary Sciences

Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells

Julia Bergild McBrien et al.

NATURE (2020)

Article Multidisciplinary Sciences

Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo

Christopher C. Nixon et al.

NATURE (2020)

Article Medicine, Research & Experimental

Persistence of an intact HIV reservoir in phenotypically naive T cells

Emmanuele Venanzi Rullo et al.

JCI INSIGHT (2020)

Article Multidisciplinary Sciences

Characterization of Nef expression in different brain regions of SIV-infected macaques

Shadan S. Yarandi et al.

PLOS ONE (2020)

Article Microbiology

The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections

Alexandra M. Bender et al.

CELL HOST & MICROBE (2019)

Review Immunology

Targeting Cellular and Tissue HIV Reservoirs With Toll-Like Receptor Agonists

Amanda B. Macedo et al.

FRONTIERS IN IMMUNOLOGY (2019)

Article Medicine, Research & Experimental

TLR7 agonist administration to SIV-infected macaques receiving early initiated cART does not induce plasma viremia

Gregory Q. Del Prete et al.

JCI INSIGHT (2019)

Review Medicine, Research & Experimental

Novel Latency Reversal Agents for HIV-1 Cure

Adam M. Spivak et al.

ANNUAL REVIEW OF MEDICINE, VOL 69 (2018)

Article Immunology

Ultrasensitive Immunoassay for Simian Immunodeficiency Virus p27CA

Adrienne E. Swanstrom et al.

AIDS RESEARCH AND HUMAN RETROVIRUSES (2018)

Article Multidisciplinary Sciences

Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane

Zheng Wang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Multidisciplinary Sciences

Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys

Erica N. Borducchi et al.

NATURE (2018)

Article Multidisciplinary Sciences

Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy

James B. Whitney et al.

NATURE COMMUNICATIONS (2018)

Review Immunology

Immune checkpoint blockade in infectious diseases

Michelle N. Wykes et al.

NATURE REVIEWS IMMUNOLOGY (2018)

Article Immunology

In Vivo Models of Human Immunodeficiency Virus Persistence and Cure Strategies

Christopher C. Nixon et al.

JOURNAL OF INFECTIOUS DISEASES (2017)

Article Immunology

Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque

Mauricio A. Martins et al.

AIDS RESEARCH AND HUMAN RETROVIRUSES (2017)

Article Multidisciplinary Sciences

Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys

Erica N. Borducchi et al.

NATURE (2016)

Article Biochemistry & Molecular Biology

International AIDS Society global scientific strategy: towards an HIV cure 2016

Steven G. Deeks et al.

NATURE MEDICINE (2016)

Review Immunology

Animal models to achieve an HIV cure

Nitasha Kumar et al.

CURRENT OPINION IN HIV AND AIDS (2016)

Article Medicine, Research & Experimental

Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques

Luca Micci et al.

JOURNAL OF CLINICAL INVESTIGATION (2015)

Article Immunology

A Murine Viral Outgrowth Assay to Detect Residual HIV Type 1 in Patients With Undetectable Viral Loads

Kelly A. Metcalf Pate et al.

JOURNAL OF INFECTIOUS DISEASES (2015)

Article Immunology

Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies

Amanda M. Crooks et al.

JOURNAL OF INFECTIOUS DISEASES (2015)

Article Veterinary Sciences

Development of SHIVs with circulating, transmitted HIV-1 variants

Amit Sharma et al.

JOURNAL OF MEDICAL PRIMATOLOGY (2015)

Article Biochemical Research Methods

Whole-body immuno PET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques

Philip J. Santangelo et al.

NATURE METHODS (2015)

Review Immunology

Molecular and cellular insights into T cell exhaustion

E. John Wherry et al.

NATURE REVIEWS IMMUNOLOGY (2015)

Article Multidisciplinary Sciences

Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys

James B. Whitney et al.

NATURE (2014)

Article Biochemistry & Molecular Biology

HIV-1 persistence in CD4+ T cells with stem cell like properties

Maria J. Buzon et al.

NATURE MEDICINE (2014)

Review Multidisciplinary Sciences

Immunologic strategies for HIV-1 remission and eradication

Dan H. Barouch et al.

SCIENCE (2014)

Article Medicine, Research & Experimental

Superior T memory stem cell persistence supports long-lived T cell memory

Enrico Lugli et al.

JOURNAL OF CLINICAL INVESTIGATION (2013)

Article Multidisciplinary Sciences

Immune clearance of highly pathogenic SIV infection

Scott G. Hansen et al.

NATURE (2013)

Review Immunology

The noncanonical NF-κB pathway

Shao-Cong Sun

IMMUNOLOGICAL REVIEWS (2012)

Article Pathology

RNAscope A Novel in Situ RNA Analysis Platform for Formalin-Fixed, Paraffin-Embedded Tissues

Fay Wang et al.

JOURNAL OF MOLECULAR DIAGNOSTICS (2012)

Article Multidisciplinary Sciences

Enhancing SIV-specific immunity in vivo by PD-1 blockade

Vijayakumar Velu et al.

NATURE (2009)

Article Biochemistry & Molecular Biology

HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation

Nicolas Chomont et al.

NATURE MEDICINE (2009)

Article Genetics & Heredity

MHC class I A region diversity and polymorphism in macaque species

Nel Otting et al.

IMMUNOGENETICS (2007)

Article Cell Biology

MIC gene polymorphism and haplotype diversity in rhesus macaques

G. G. M. Doxiadis et al.

TISSUE ANTIGENS (2007)

Article Biochemistry & Molecular Biology

Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells

JD Siliciano et al.

NATURE MEDICINE (2003)