Objective To report a case of persistent infection by varicella-zoster virus (VZV) in an HIV-infected patient who presented with atypical, hyperkeratotic viral lesions and a partial response to acyclovir.Methods Viral changes found on histopathological examination; definitive diagnosis of VZV infection was established by viral culture.Results Lesions of chronic hyperkeratotic herpes zoster responded partially to acyclovir therapy, and complete resolution was achieved with intravenous foscarnet. Absence of visceral involvement.Conclusion Prolonged acyclovir therapy for herpes virus infections in HIV-seropositive patients may represent an important pathogenic factor for the appearance of atypical clinical forms associated with drug-resistant viral strains.