TLR7 Agonist GS–9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIV[sub.SF162P3]-Infected Rhesus Monkeys
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 i...
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Published in | Biomedicines Vol. 11; no. 6 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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01.06.2023
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Abstract | 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 SHIV[sub.SF162P3]-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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AbstractList | 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 SHIV[sub.SF162P3]-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. |
Audience | Academic |
Author | Zhang, Jingjing Wang, Wei Xue, Jing Sun, Yuting Cong, Zhe Dang, Cui Wei, Qiang Chen, Ting Yang, Chenbo Lu, Jiahan |
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Snippet | 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... |
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SubjectTerms | Antiviral agents Care and treatment Health aspects Highly active antiretroviral therapy HIV infection Infection Niacinamide |
Title | TLR7 Agonist GS–9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIV[sub.SF162P3]-Infected Rhesus Monkeys |
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