The patient began treatment for HSV, and despite successive 1-month courses of high-dose oral acyclovir, valacyclovir, and famciclovir, his lesions progressed. A repeated tissue culture for viral resistance testing was not successful in growing virus. A repeated biopsy confirmed the original diagnosis of verrucous HSV. Given concern for acyclovir-resistant HSV, oral therapy was discontinued, and intravenous (IV) cidofovir treatment was initiated, with improvement noted after 3 doses. This treatment was complicated by elevations in serum creatinine levels and discontinued. Intralesional cidofovir was then initiated every other week, as previously reported,1 with resolution of his scrotal lesion and dramatic improvement in his perianal lesion after 6 treatments (Figure 1C and D).