Sorivudine versus Acyclovir for Treatment of Dermatomal Herpes Zoster in Human Immunodeficiency Virus-Infected Patients: Results from a Randomized, Controlled Clinical Trial

Abstract

The present randomized, double-blind, placebo-controlled, multicenter clinical trial was designed to compare the efficacy and tolerability of sorivudine [1-β-d-arabinofuranosyl-E-(2-bromovinyl)uracil] and acyclovir for the treatment of dermatomal herpes zoster in human immunodeficiency virus (HIV)-seropositive patients. A total of 170 HIV-seropositive adults presenting with herpes zoster (confirmed by direct fluorescent-antigen testing and/or viral culture) were enrolled and randomized to receive a 10-day course of orally administered sorivudine (40 mg once daily plus acyclovir placebos) or acyclovir (800 mg five times daily plus sorivudine placebo). Patients were monitored daily to document the events of cutaneous healing, pain, zoster-related complications, and drug-related adverse events. Patients were reassessed on days 21 and 28 and then once monthly for 1 year. The primary efficacy endpoint was time to the cessation of new vesicle formation. Secondary efficacy endpoints included times to other events of cutaneous healing, resolution of pain, and frequency of dissemination and zoster recurrence. In a multivariate analysis, sorivudine was superior to acyclovir for reducing the times to the cessation of new vesicle formation (relative risk [RR] = 1.54, 95% confidence interval [CI] = 1.00 to 2.36; P = 0.049) and total lesion crusting (RR = 1.48, 95% CI = 1.07 to 2.04;P = 0.017). In a univariate analysis, there was a trend favoring sorivudine for the cessation of new vesicle formation (median of 3 versus 4 days; P = 0.07) and a significant advantage for time to total lesion crusting (median of 7 versus 8 days; P = 0.02). The time to the resolution of zoster-associated pain, the frequency of dissemination, and the frequency of zoster recurrence were not different between the two treatment groups. Both drugs were well tolerated. Sorivudine is an effective drug for the treatment of herpes zoster in HIV-infected patients and results in accelerated cutaneous healing when compared with acyclovir therapy.

Recommendations for the Management of Herpes Zoster

“…Prospectively acquired data to guide clinicians when selecting antiviral therapy for HZ in HIV-seropositive patients are currently limited. Nearly 300 HIV-infected patients with HZ were enrolled in controlled studies comparing orally administered acyclovir (800 mg 5 times daily) with sorivudine (40 mg once daily) [202,203]. Times to cessation of new vesicle formation, total crusting, and resolution of HZ-associated pain were 3-4 days, 7-8 days, and ∼60 days, respectively [203].…”

“…Nearly 300 HIV-infected patients with HZ were enrolled in controlled studies comparing orally administered acyclovir (800 mg 5 times daily) with sorivudine (40 mg once daily) [202,203]. Times to cessation of new vesicle formation, total crusting, and resolution of HZ-associated pain were 3-4 days, 7-8 days, and ∼60 days, respectively [203]. Although sorivudine was never marketed, these studies clearly confirmed the efficacy and safety of oral antiviral therapy for HZ in patients with HIV infection.…”

The cancer patient with chronic pain due to herpes zoster

“…Sorivudine at 40 mg per day for 7 days is 1000-fold more active than acyclovir against VZV in vitro, and was also compared directly with acyclovir in a randomized, blinded, placebo-controlled trial in patients with HIV with zoster [30]. Although this nucleoside analog was superior to acyclovir in terms of time to cessation of new vesicle formation and lesion crusting, the time to resolution of zoster-associated pain was not different between the two arms.…”

“…Although this nucleoside analog was superior to acyclovir in terms of time to cessation of new vesicle formation and lesion crusting, the time to resolution of zoster-associated pain was not different between the two arms. Due to severe myelotoxicity with concurrent administration of sorivudine and 5-fluorouracil chemotherapy, these two treatments should not be given together [30]. In summary, early therapy (initiated within 72 hours of rash onset) with antiviral agents prevents or attenuates the occurrence of PHN for some patients; however, a substantial number of patients still develop chronic pain and may benefit from adjunctive medications with different mechanisms of action.…”

Lanreotide Autogel®in acromegaly and neuroendocrine tumors

“…A randomized, controlled trial demonstrated oral acyclovir to be effective for dermatomal zoster in HIV-infected patients, facilitating healing and shortening the time of zoster-associated pain [74]. Its use in cases of varicella zoster IRIS appears to be of clinical benefit [18].…”