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

Bricker, Katherine M.; Chahroudi, Ann; Mavigner, Maud

doi:10.3390/v13081560

Cited by 10 publications

(4 citation statements)

References 100 publications

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“…Reactivation and subsequent depletion ("shock and kill") of the virus in latent reservoirs has been one therapeutic strategy [23][24][25], while manipulation of the signaling pathways necessary for latency establishment has been another strategy [26]. It is important to highlight that despite the use of all these techniques, cART has not yet completely eliminated or eradicated the virus [27].…”

Section: Antiretroviralsmentioning

confidence: 99%

Antiviral Targets and Known Antivirals (HAART)

Helen Ifedilichukwu,

Joy

2023

Infectious Diseases

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In 2021, the number of HIV-positive people worldwide was estimated to be 38.4 million. Since its discovery four decades ago, the scope of the HIV infection has outstripped all predictions, necessitating the urgent need to develop novel antivirals against the virus that target crucial stages in the virus’ life cycle. New antiviral drug classes that were developed in response to the HIV epidemic were coupled to offer very highly active antiretroviral treatment. These novel highly active antiretroviral therapies (HAART) were developed as a result of the emergence of drug-resistant strains of the virus. By inhibiting these enzymes, reverse transcriptase, integrase, and protease that are essential for viral attachment, entry, integration, and maturation, antiretroviral therapy (ART) strategies can suppress the virus, lower the viral load, boost CD4 count, and ultimately halt the progression of the disease. Advances in research on the biology of both the immature and the mature forms of the HIV capsid in terms of its structure and function have made it possible to discover and/or design small molecules and peptides that interfere with the virus’s assembly and maturation. This article presents and reviews HAART’s current state and strategies as a very active antiviral.

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Section: Antiretroviralsmentioning

confidence: 99%

Antiviral Targets and Known Antivirals (HAART)

Helen Ifedilichukwu,

Joy

2023

Infectious Diseases

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“…Finally, our group has provided a proof-of-concept that Vδ2 T cells may be incorporated into current strategies for HIV cure within virally suppressed people living with HIV [ 71 , 72 ]. One approach utilized in HIV cure strategies encompasses reactivation of latent virus using small compounds generally called latency reversing agents and boosting immune responses [ 73 , 74 , 75 , 76 , 77 , 78 ]. We demonstrated that autologous expanded Vδ2 T cells mediated killing of latently HIV-infected CD4+ T cell reservoirs upon reactivation.…”

Section: Clinical Applications Of Vδ2 T Cell Immunotherapymentioning

confidence: 99%

Human Vδ2 T Cells and Their Versatility for Immunotherapeutic Approaches

Sanz

Mann

Chitrakar

et al. 2022

Cells

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Gamma/delta (γδ) T cells are innate-like immune effectors that are a critical component linking innate and adaptive immune responses. They are recognized for their contribution to tumor surveillance and fight against infectious diseases. γδ T cells are excellent candidates for cellular immunotherapy due to their unique properties to recognize and destroy tumors or infected cells. They do not depend on the recognition of a single antigen but rather a broad-spectrum of diverse ligands through expression of various cytotoxic receptors. In this manuscript, we review major characteristics of the most abundant circulating γδ subpopulation, Vδ2 T cells, their immunotherapeutic potential, recent advances in expansion protocols, their preclinical and clinical applications for several infectious diseases and malignancies, and how additional modulation could enhance their therapeutic potential

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“…Several novel LRAs under investigation certainly shed new light on HIV cure therapies [ 19 , 20 ]. In this study, seronegative SHIV SF162P3 -infected rhesus monkeys were used to evaluate the efficacy of HIV reactivation with either GS–9620 alone or a combination of GS–9620 and NAM therapy.…”

Section: Introductionmentioning

confidence: 99%

TLR7 Agonist GS–9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIVSF162P3-Infected Rhesus Monkeys

Cong,

Sun,

Dang

et al. 2023

Biomedicines

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Antiretroviral therapy is capable of inhibiting HIV replication, but it fails to completely achieve a cure due to HIV persistence. The commonly used HIV cure approach is the “shock and kill” strategy, which employs latency-reversing agents to trigger viral reactivation and boost cellular immunity. Finding the appropriate drug combination for the “shock and kill” strategy would greatly facilitate clinical trials. The toll-like receptor (TLR) 7 agonist GS–9620 and nicotinamide (NAM) are reported as potential latency-reversing agents. Herein, we found the absence of viral reactivation when SHIVSF162P3-aviremic rhesus macaques were treated with GS–9620 monotherapy. However, our findings demonstrate that viral blips emerged in half of the macaques treated with the combination therapy of GS–9620 and NAM. Notably, an increase in the reactivation of the replication-competent latent virus was measured in monkeys treated with the combination therapy. These findings suggest that the GS–9620 and NAM combination could be used as a multipronged HIV latency stimulation approach, with potential for optimizing antiviral therapy design.

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

Cited by 10 publications

References 100 publications

Antiviral Targets and Known Antivirals (HAART)

Antiviral Targets and Known Antivirals (HAART)

Human Vδ2 T Cells and Their Versatility for Immunotherapeutic Approaches

TLR7 Agonist GS–9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIVSF162P3-Infected Rhesus Monkeys

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