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

Ann Intern Med. 1998 Jan 1;128(1):21-8. doi: 10.7326/0003-4819-128-1-199801010-00004.


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 dairy 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Aminopurine / analogs & derivatives*
  • 2-Aminopurine / therapeutic use
  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / virology
  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antiviral Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Cross-Over Studies
  • Double-Blind Method
  • Famciclovir
  • Female
  • Herpes Simplex / drug therapy*
  • Herpes Simplex / virology
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Regression Analysis
  • Simplexvirus / growth & development
  • Virus Activation
  • Virus Shedding


  • Antibodies, Viral
  • Antiviral Agents
  • 2-Aminopurine
  • Famciclovir