The In Vitro Evaluation of the Virucidal Efficacy of Povidone-Iodine against Multiple Ocular Adenoviral Types

Abstract

Purpose: Povidone-iodine (P-I) has been proposed as a topical antiviral for adenoviral (Ad) ocular infections. Several concentrations have been tested for potential clinical use: 5% (Betadine for EKC Study, www.betadineforekc.com); 2% (clinical trial NCT01179412); 0.4% (as part of the 0.4% P-I/0.1% dexamethasone combination, clinical trial NCT01470664). The in vitro efficacy of P-I against Ad has been shown for various concentrations using a limited number of Ad types. The goal of the current study was to determine the in vitro efficacy of the clinically proposed concentrations of P-I against a panel of common ocular Ad types.

Methods: The virucidal efficacy of 5%, 2%, 0.4%, and 0.001% P-I and a negative control was determined for extracellular adenovirus of types Ad3, Ad4, Ad5, Ad7a, Ad8, Ad19, and Ad37. Ad/P-I mixtures were incubated at 33^oC. At 1, 5, 15, and 60 minutes of incubation, aliquots were removed and added to equal volumes of 0.2 N sodium thiosulfate solution to neutralize the P-I. These solutions were incubated at room temperature for 5 minutes after which equal volumes of tissue culture media were added. Standard viral titrations were carried out on these samples to determine the amount of virus present. The viral titers were calculated and Log₁₀ converted. Virucidal (99.9%) decreases in titers compared with the negative controls were determined for each P-I concentration, time and Ad type.

Results: Virucidal decreases in Ad titers were demonstrated for 5%, 2%, and 0.4% P-I at 1 minute for Ad3, Ad4, Ad5, Ad7a, and Ad8. For Ad19, virucidal decreases were demonstrated at 60 minutes for 5% P-I, 1 minute for 2% P-I, and 15 minutes for 0.4% P-I whereas for Ad37, virucidal decreases were demonstrated at 60 minutes for 5% P-I, 60 minutes for 2% P-I, but 1 minute for 0.4% P-I. No virucidal decreases in Ad titers were demonstrated for 0.001% P-I at any time point for any serotype.

Conclusions: Tested P-I concentrations were virucidal at 1 minute for most of the ocular serotypes tested. However, the time to achieve a virucidal decrease for the EKC types Ad19 and Ad37 increased for several P-I concentrations. The efficacy of P-I in the treatment of ocular adenoviral infections may be type dependent.

Keywords: 411 adenovirus • 425 antiviral drugs • 475 conjunctivitis