Anti-HIV
microbicides are being investigated in clinical trials and understanding how promising strategies work, coincident with demonstrating efficacy in vivo, is central to advancing new generation
microbicides. We evaluated Carraguard and a new generation Carraguard-based formulation containing the non-
nucleoside reverse transcriptase inhibitor (NNRTI)
MIV-150 (PC-817). Since dendritic cells (DCs) are believed to be important in HIV transmission, the formulations were tested for the ability to limit DC-driven
infection in vitro versus vaginal
infection of macaques with RT-SHIV (SIVmac239 bearing
HIV reverse transcriptase). Carraguard showed limited activity against cell-free and mature DC-driven RT-SHIV
infections and, surprisingly, low doses of Carraguard enhanced
infection. However, nanomolar amounts of
MIV-150 overcame enhancement and blocked DC-transmitted
infection. In contrast, Carraguard impeded
infection of immature DCs coincident with DC maturation. Despite this variable activity in vitro, Carraguard and
PC-817 prevented vaginal transmission of RT-SHIV when applied 30 min prior to challenge.
PC-817 appeared no more effective than Carraguard in vivo, due to the limited activity of a single dose of
MIV-150 and the dominant barrier effect of Carraguard. However, 3 doses of
MIV-150 in placebo gel at and around challenge limited vaginal
infection, demonstrating the potential activity of a topically applied NNRTI. These data demonstrate discordant observations when comparing in vitro and in vivo efficacy of Carraguard-based
microbicides, highlighting the difficulties in testing putative anti-viral strategies in vitro to predict in vivo activity. This work also underscores the potential of Carraguard-based formulations for the delivery of anti-viral drugs to prevent vaginal
HIV infection.