Prolonged release and antiviral efficacy of HIV fusion inhibitor LP-98-loaded microspheres in rhesus macaques

Non-adherence to antiretroviral treatment is a critical obstacle to effectively managing the progression of AIDS and reducing transmission and mortality rates. A promising strategy to address the clinical disadvantages of user-dependent dosing and decrease medication frequency is the development of long-acting antiretrovirals. In this study, we fabricated PLGA microspheres (MS) incorporating the lipopeptide LP-98 (LP-98-MS), which has previously exhibited potent anti-HIV efficacy. Our findings demonstrate that a single-dose injection of LP-98-MS in SHIV-infected rhesus macaques resulted in sustained and gradual release, maintaining antiviral effects at least 28 days. Notably, a single administration of LP-98-MS provided more than 28 days of sustained release, resulting in high-level pre-exposure prophylaxis (PrEP) for rhesus macaques, even providing complete protection when exposed to repeated intravaginal and intrarectal SHIV challenges. Overall, LP-98-MS holds significant potential in reducing medication frequency and shows promising prospects for further development.