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 co mmon opportunistic infections in HIV-infected persons. However, most d ocumentation of the effectiveness of antiviral therapy in reducing HSV reactivation is anecdotal. Objective: To evaluate the quantitative ef fect 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 seropositi ve. Intervention: Patients were randomly assigned to receive famciclov ir, 500 mg orally twice dairy, or placebo for 8 weeks. They then cross ed over to receive the other regimen after a 1-week washout period. Me asurements: Patients obtained daily cultures of their perirectal, uret hral, oral, and genital areas and kept diary records of signs and symp toms of genital and oral-labial herpes. Results: The median CD4 cell c ount at study entry was 384 cells/mm(3). In the intention-to-treat ana lysis 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 famciclovi r 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 wi th HSV-2 shedding was reduced from 9.7% to 1.3%. Breakthrough reactiva tions that occurred while patients were receiving famciclovir were inf requent, short, and often asymptomatic; HSV-2 isolates from these reac tivations were susceptible to penciclovir in vitro. Conclusions: Antiv iral chemotherapy with famciclovir results in clinically and statistic ally significant reductions in the symptoms associated with HSV infect ion and the symptomatic and asymptomatic shedding of HSV among HIV-pos itive persons.