TLR7 Agonist GS–9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIV[sub.SF162P3]-Infected Rhesus Monkeys

• Published in: Biomedicines Vol. 11; no. 6
• Main Authors: Cong, Zhe, Sun, Yuting, Dang, Cui, Yang, Chenbo, Zhang, Jingjing, Lu, Jiahan, Chen, Ting, Wei, Qiang, Wang, Wei, Xue, Jing
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.06.2023
• Subjects: Antiviral agents; Care and treatment; Health aspects; Highly active antiretroviral therapy; HIV infection; Infection; Niacinamide; China
• DOI: 10.3390/biomedicines11061707
• ISSN: 2227-9059

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.