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Famciclovir for the Suppression of Symptomatic and Asymptomatic Herpes Simplex Virus Reactivation in HIV-Infected Persons: A Double-Blind, Placebo-Controlled Trial
- Timothy Schacker, MD;
- Hui-lin Hu, PhD;
- David M. Koelle, MD;
- Judith Zeh, PhD;
- Robin Saltzman, MD;
- Ron Boon, BSc;
- Mary Shaughnessy, RN;
- Gail Barnum, ARNP; and
- Lawrence Corey, MD
- From University of Washington, Seattle, Washington; and Smith-Kline Beecham Pharmaceuticals, Philadelphia, Pennsylvania. Acknowledgments: The authors thank Gill Atkinson, Regina Jurewicz, and Christine Fletcher for support during the conduct and analysis of the trial; Klaus Esser of Smith-Kline Beecham Pharmaceuticals for supplying penciclovir; Aimee Ekstrom for assistance with antiviral susceptibility assays; Romesh Goutom, PhD, for assistance with assay validation; Stacy Selke for managing the data and providing files for statistical analysis; and the study participants for their time and commitment. Grant Support: In part by National Institutes of Health grant AI-01228 and a grant from SmithKline Beecham Pharmaceuticals. Requests for Reprints: Lawrence Corey, MD, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, M115, Seattle, WA 98104. Current Author Addresses: Dr. Schacker: University of Minnesota, 516 Delaware Street, Box 250, Minneapolis, MN 55455.
Abstract
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.
- Copyright ©2004 by the American College of Physicians
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