TY - JOUR
T1 - Topical effects of cidofovir on cutaneous rabbit warts
T2 - Treatment regimen and inoculum dependence
AU - Duan, Jianmin
AU - Paris, William
AU - De Marte, Josie
AU - Roopchand, Diana
AU - Fleet, Tamara Louise
AU - Cordingley, Michael G.
PY - 2000/5
Y1 - 2000/5
N2 - The present study examined topical effects of cidofovir on cutaneous rabbit warts. Based on an inoculum-dependency study, each New Zealand White rabbit was inoculated with a high and low titer of cottontail rabbit papillomavirus (CRPV) at four sites on each dorsolateral area. Inoculation with 50 ID50 induced papillomas at 100% of the inoculation sites within 16 ± 1 days, and the wart growth curve plateaued within ˜ 7 weeks. With an inoculum of 5 ID50, 80% of the inoculated sites developed papillomas within 21 ± 1 days and their size plateaued at a later time. Cidofovir was applied topically twice daily on the inoculated sites at a concentration of 1% for 18 days, starting at three different time points. In the first experiment, treatment was initiated 7 days post-inoculation. One of the inoculated sides received cidofovir or the vehicle, PBS, while the other side was left untreated. With this treatment regimen, cidofovir significantly delayed the time of onset and the growth rate of papillomas induced with the high titer of inoculum. It completely prevented papilloma-induction on the sites inoculated with the low titer of CRPV. Reversible side-effects of cidofovir were observed on the directly treated area including erythema, necrosis, and flaking. Both therapeutic and side-effects were limited to the sites of direct exposure. In the second experiment, one of the two sides in each group of rabbits received cidofovir or vehicle starting on day 29 post-inoculation. With this treatment regimen, cidofovir significantly reduced wart growth against the low titer only. Topical treatment initiated on day 49 post- inoculation was not effective on warts initiated with either viral titer. These results demonstrated that topical cidofovir could be very effective against papillomavirus-induced wart growth if it is initiated early during the infection, especially against low titers of inoculum.
AB - The present study examined topical effects of cidofovir on cutaneous rabbit warts. Based on an inoculum-dependency study, each New Zealand White rabbit was inoculated with a high and low titer of cottontail rabbit papillomavirus (CRPV) at four sites on each dorsolateral area. Inoculation with 50 ID50 induced papillomas at 100% of the inoculation sites within 16 ± 1 days, and the wart growth curve plateaued within ˜ 7 weeks. With an inoculum of 5 ID50, 80% of the inoculated sites developed papillomas within 21 ± 1 days and their size plateaued at a later time. Cidofovir was applied topically twice daily on the inoculated sites at a concentration of 1% for 18 days, starting at three different time points. In the first experiment, treatment was initiated 7 days post-inoculation. One of the inoculated sides received cidofovir or the vehicle, PBS, while the other side was left untreated. With this treatment regimen, cidofovir significantly delayed the time of onset and the growth rate of papillomas induced with the high titer of inoculum. It completely prevented papilloma-induction on the sites inoculated with the low titer of CRPV. Reversible side-effects of cidofovir were observed on the directly treated area including erythema, necrosis, and flaking. Both therapeutic and side-effects were limited to the sites of direct exposure. In the second experiment, one of the two sides in each group of rabbits received cidofovir or vehicle starting on day 29 post-inoculation. With this treatment regimen, cidofovir significantly reduced wart growth against the low titer only. Topical treatment initiated on day 49 post- inoculation was not effective on warts initiated with either viral titer. These results demonstrated that topical cidofovir could be very effective against papillomavirus-induced wart growth if it is initiated early during the infection, especially against low titers of inoculum.
KW - Cidofovir
KW - Cottontail rabbit papillomavirus (CRPV)
KW - Papilloma
KW - Rabbits
KW - Warts
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U2 - 10.1016/S0166-3542(00)00080-2
DO - 10.1016/S0166-3542(00)00080-2
M3 - Article
C2 - 10854665
AN - SCOPUS:0034040643
VL - 46
SP - 135
EP - 144
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 2
ER -