The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

Scientists and clinicians attending the last "New Directions in Antiviral Therapy" conference in late 1994 could hardly have predicted the revolution in the management of patients with HIV infection that has occurred since. Two new classes of antiretrovirals have been licensed, the second-site RT inhibitors and the protease inhibitors; the long in cubation period of active HIV infection, when the infection is clinically latent, is now un derstood to be a period of intense viral replication and turnover of CD4 lymphocytes; measurements of HI V RNA concentration in plasma have been shown to be essential tools for monitoring the course of HIV infection, deciding when to treat, and assessing the re sults of treatment; and finally, combinations of antiretrovirals, particularly combinations including protease inhibitors, have been shown to have dramatically beneficial effects on patients with HIV infection. These advances, coupled with new drugs for the management of herpesvirus infections, have made dramatic differences in the quality and length of life of HIV-infected patients. Additional advances have been made since 1994 in the prevention or management of influenza virus (zanamavir), respiratory syncytial virus (palvizumab), hepatitis B virus (lamivudine and famciclovir), and enterovirus infections (pleconaril). It is difficult to re member that only slightly more than a decade ago there were only a handful of antiviral agents available (none of which were antiretrovirals), and a number of those were either highly toxic, of dubious efficacy, or both."

Scientists and clinicians attending the last "New Directions in Antiviral Therapy" conference in late 1994 could hardly have predicted the revolution in the management of patients with HIV infection that has occurred since. Two new classes of antiretrovirals have been licensed, the second-site RT inhibitors and the protease inhibitors; the long in cubation period of active HIV infection, when the infection is clinically latent, is now un derstood to be a period of intense viral replication and turnover of CD4 lymphocytes; measurements of HI V RNA concentration in plasma have been shown to be essential tools for monitoring the course of HIV infection, deciding when to treat, and assessing the re sults of treatment; and finally, combinations of antiretrovirals, particularly combinations including protease inhibitors, have been shown to have dramatically beneficial effects on patients with HIV infection. These advances, coupled with new drugs for the management of herpesvirus infections, have made dramatic differences in the quality and length of life of HIV-infected patients. Additional advances have been made since 1994 in the prevention or management of influenza virus (zanamavir), respiratory syncytial virus (palvizumab), hepatitis B virus (lamivudine and famciclovir), and enterovirus infections (pleconaril). It is difficult to re member that only slightly more than a decade ago there were only a handful of antiviral agents available (none of which were antiretrovirals), and a number of those were either highly toxic, of dubious efficacy, or both."

The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.