AIDS research and human retroviruses 2017 02 08() doi 10.1089/AID.2016.0199
In the absence of an effective vaccine, strategies to prevent HIV transmission are urgently needed. Condomless receptive anal intercourse represents a major route of transmission, and efforts are being made to develop strategies in which potent anti-HIV drugs are formulated for topical application to the rectum prior to sex. 5P12-RANTES is a promising candidate for such a purpose. It is an analogue of the human chemokine RANTES/CCL5, which potently blocks CCR5, the principal coreceptor used by HIV to enter and infect target cells. As a protein, 5P12-RANTES is potentially vulnerable to attack by proteases in the rectal environment. Here we tested the stability of 5P12-RANTES on exposure to rectal lavage samples obtained from healthy volunteers, using a sensitive HIV entry inhibition assay as an indicator of stability. Varying levels of inactivating activity towards 5P12-RANTES were detected across the different lavage samples. Analysis of even the most aggressive samples indicated that protease activity in the rectal environment is unlikely to impact on the anti-HIV activity of 5P12-RANTES when applied pericoitally at the envisaged clinical dose (1 mM). This study indicates that 5P12-RANTES has adequate stability for further development as an HIV prevention drug for rectal use.