Efficient Treatment and Pre-Exposure Prophylaxis in Rhesus Macaques by an HIV Fusion-Inhibitory Lipopeptide

Two new HIV fusion-inhibitory lipopeptides (LP-97 and LP-98) were designed with extremely potent and long-acting antiviral activity, and monotherapy with a low-dose LP-98 sharply reduced viral load and maintained long-term viral suppression in SHIVSF162P3-infected 21 rhesus macaques. Promisingly, we found that five treated monkeys achieved posttreatment control (PTC) efficacy and they hided lower viral DNA in deep lymph nodes, whereas monkeys with stable viral rebound had higher viral DNA in superficial lymph nodes. Tissues of the PTC monkeys also exhibited significantly decreased quantitative viral outgrowth (QVOA) and fewer PD-1+ central memory CD4+ T cells, and CD8+ T cells critically contributed the PTC efficacy. Moreover, LP-98 when administrated as pre-exposure prophylaxis (PrEP) provided complete protection in 46 monkeys against SHIVSF162P3 and SIVmac239 infections via intrarectal, intravaginal or intravenous challenge. In conclusion, such lipopeptides possess high potential to achieve functional HIV cure and prevention.