Abstract
Microbicides have been evaluated mostly against cell-free HIV-1. Because semen contains both cell-free and cell-associated HIV-1, HIV-1 transmission could occur via either or both sources. Therefore, it is important to examine the antiviral activity of microbicides against cell-associated HIV-1. The cyclic antimicrobial peptide retrocyclin RC-101 has been shown previously to have antiviral activity against cell-free HIV-1, with no associated cellular toxicity. In this article we have examined the antiviral activity of RC-101 against cell-associated HIV-1. The results demonstrate potent antiviral activity of RC-101 against cell-cell HIV-1 transmission in both CD4-dependent and CD4-independent assays against CCR5- and CXCR4-tropic HIV-1, with no cellular toxicity. Furthermore, this antiviral activity was retained in the presence of human seminal plasma. The potent antiviral activity of RC-101 against cell-associated HIV-1 reported here, and the previously reported antiviral activity in cervical tissues, suggest that RC-101 is an excellent and promising microbicide candidate against HIV-1.