Cong Zhe, Sun Yuting, Dang Cui, Yang Chenbo, Zhang Jingjing, Lu Jiahan, Chen Ting, Wei Qiang, Wang Wei, Xue Jing
MOH Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Comparative Medicine Center, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Biomedicines. 2023 Jun 14;11(6):1707. doi: 10.3390/biomedicines11061707.
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-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.
抗逆转录病毒疗法能够抑制HIV复制，但由于HIV的持续存在，它无法完全治愈疾病。常用的HIV治愈方法是“激活并清除”策略，该策略使用潜伏逆转剂来触发病毒重新激活并增强细胞免疫力。找到适合“激活并清除”策略的药物组合将极大地促进临床试验。Toll样受体（TLR）7激动剂GS-9620和烟酰胺（NAM）被报道为潜在的潜伏逆转剂。在此，我们发现接受GS-9620单药治疗的无病毒血症的恒河猴没有出现病毒重新激活。然而，我们的研究结果表明，在接受GS-9620和NAM联合治疗的猕猴中，有一半出现了病毒波动。值得注意的是，在用联合疗法治疗的猴子中，检测到有复制能力的潜伏病毒的重新激活有所增加。这些发现表明，GS-9620和NAM联合疗法可作为一种多管齐下的HIV潜伏激活方法，具有优化抗病毒治疗设计的潜力。
