Nanoformulations of Rilpivirine for Topical Pericoital and Systemic Coitus-Independent Administration Efficiently Prevent HIV Transmission

• DOI: 10.1371/journal.ppat.1005075
• Publication Date: 2015-08-13T18:10:24Z
• Authors: Martina Kovarova; Olivia D. Council; Abhijit A. Date; Julie M. Long; Tomonori Nochii; Michael Belshan; Annemarie Shibata; Heather Vincent; Caroline E. Baker; William O. Thayer; Guenter Kraus; Sophie Lachaud-Du...; Peter Williams; Christopher J. De...; J. Victor Garcia
• Keywords: Rilpivirine; Antiretroviral drug; Dolutegravir; Sexual transmission

Vaginal HIV transmission accounts for the majority of new infections worldwide. Currently, multiple efforts to prevent are based on pre-exposure prophylaxis with various antiretroviral drugs. Here, we describe two novel nanoformulations reverse transcriptase inhibitor rilpivirine pericoital and coitus-independent prevention. Topically applied rilpivirine, encapsulated in PLGA nanoparticles, was delivered a thermosensitive gel, which becomes solid at body temperature. nanoparticles coated reproductive tract offered significant protection BLT humanized mice from vaginal high-dose HIV-1 challenge. A different nanosuspension crystalline (RPV LA), administered intramuscularly, protected single challenge one week after drug administration. Using transmitted/founder viruses, were previously shown establish de novo infection humans, demonstrated that RPV LA offers consecutive challenges four weeks In this experiment, also showed that, certain cases, even presence drug, could occur without overt or detectable systemic replication until levels reduced. We can result acquisition viruses subsequent exposures. These observations have important implications implementation long-acting formulations They provide first evidence occult occur, despite sustained Together, our results demonstrate topically- systemically coitus-dependent infection.