Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons: A double-blind, placebo- controlled trial

Background: Herpes simplex virus (HSV) infection is one of the most common opportunistic infections in HIV-infected persons. However, most documentation of the effectiveness of antiviral therapy in reducing HSV reactivation is anecdotal. Objective: To evaluate the quantitative effect of antiviral therapy on the frequency of HSV reactivation in HIV-infected persons. Design: Double-blind, placebo-controlled, crossover trial. Setting: Research clinic at a university hospital. Patients: 48 persons (45 men and 3 women) who were HIV positive and HSV seropositive. Intervention: Patients were randomly assigned to receive famciclovir, 500 mg orally twice daily, or placebo for 8 weeks. They then crossed over to receive the other regimen after a 1-week washout period. Measurements: Patients obtained daily cultures of their perirectal, urethral, oral, and genital areas and kept diary records of signs and symptoms of genital and oral-labial herpes. Results: The median CD4 cell count at study entry was 384 cells/mm³. In the intention-to-treat analysis of the first study period, HSV was isolated on 122 of 1114 (11%) placebo days compared with 9 of 1071 (1%) famciclovir days (relative risk, 0.15; P < 0.001). For patients who completed the crossover, the median difference in days with symptoms between placebo and famciclovir was 13.8% of days and the median difference in days on which HSV was isolated was 5.4% of days (P < 0.001 for both). Percentage of days with HSV-2 shedding was reduced from 9.7% to 1.3%. Breakthrough reactivations that occurred while patients were receiving famciclovir were infrequent, short, and often asymptomatic; HSV-2 isolates from these reactivations were susceptible to penciclovir in vitro. Conclusions: Antiviral chemotherapy with famciclovir results in clinically and statistically significant reductions in the symptoms associated with HSV infection and the symptomatic and asymptomatic shedding of HSV among HIV-positive persons.