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Anti-HPV and anti-HSV activity in rectal enema effluents collected from subjects receiving PC-1005: a dual compartment multipurpose prevention technology formulation

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BACKGROUND: MTN-037 is a Phase 1 dose-ranging trial evaluating the rectal safety and pharmacokinetics of PC-1005 (MIV-150, zinc acetate, carrageenan), a peri-coital gel designed for vaginal and rectal use. Pharmacodynamic studies are focused on anti-HIV activity; however, the active pharmaceutical ingredients in PC-1005 also have activity against other sexually transmitted viral infections, making it a promising multipurpose prevention technology (MPT). In an ancillary study, we tested the activity of PC-1005 against human papillomavirus type 16 pseudovirus (HPV16 PsV) and herpes simplex 2 (HSV-2) using the rectal enema effluents collected in MTN-037.
METHODS: Healthy HIV-negative research participants in MTN-037 sequentially received escalating single doses (4mL, 16mL and 32mL) of PC-1005 rectally and rectal enema effluents were collected at baseline, early (0.5-5 hours) and late (24 hours) time points. There was a washout period (14-42 days) between single doses. The anti-HPV and anti-HSV activity of enema effluents from 6 participants were evaluated using (1) the HPV16 PsV luciferase assay to estimate half-maximal effective concentrations (EC50) based on rectal enema effluent dilution and (2) the HSV-2 plaque reduction assay after incubation of rectal enema effluents with HSV-2 for 30 minutes at 37oC.
RESULTS: Rectal enema effluents in the HPV 16 PsV assay had EC50 values between 0.16 and 2.4x10-5 (dilution factor). EC50 values from enema effluents collected at early (0.5-5 hours) time points post PC-1005 gel application were significantly lower from enema effluents collected at baseline (p<0.04). The HSV-2 assay resulted in 66-87% decrease in HSV-2 plaque forming units. The anti-HSV-2 activity was significantly different between enema effluents collected at early time points (0.5-5 hours) post gel application and those collected at baseline (p<0.02). There was correlation between anti-HPV and anti-HSV activity (Spearman r=0.7409; p<0.0001).
CONCLUSIONS: Our results support the further evaluation of PC-1005 as an on-demand formulation to prevent HPV and HSV infections.