Antiviral agents, vaccines, and immunotherapies

Chapter 1. Introduction .................................................. 1 References .... 22 Chapter 2. Antiretroviral Drugs to Treat Human Immunodeficiency Virus Infections ...... 25 Introduction .... 25 Human Immunodeficiency Virus .... 27 Nucleoside Reverse Transcriptase Inhibitors .... 39 Zidovudine [AZT] (Retrovir ) .... 39 Didanosine[ddI] (Videx ) .... 42 Stavudine [d4T] (Zerit ) .... 44 Zalcitabine [ddc] (Hivid ) .... 46 Lamivudine [3TC] (Epivir ) .... 48 Abacavir [ABC] (Ziagen ) .... 50 Emtricitabine (Emtriva, Coviracil, FTC) .... 52 Non-Nucleoside Reverse Transcriptase Inhibitors .... 53 Nevirapine [NVP] (Viramune ) .... 54 Delavirdine [DLV] (Rescriptor ) .... 56 Efavirenz [EFV] (Sustiva ) .... 59 Nucleotide Reverse Transcriptase Inhibitors .... 62 Tenofovir Disproxil Fumerate (Viread ) .... 62 x Contents HIV Protease Inhibitors .... 65 Saquinavir [SQV] (Invirase : Hard Gel; Fortovase : Soft Gel) .... 67 Ritonavir [RTV] (Norvir ) .... 68 Indinavir [IDV] (Crixivan ) .... 71 Nelfinavir [NFV] (Viracept ) .... 75 Amprenavir [APV] (Agenerase ) .... 77 Fosamprenavir (Lexiva, GW 433908) .... 80 Atazanavir (Reyataz, BMS-232632) .... 83 Lopinavir + Ritonavir [ABT-378/r] (Kaletra ) .... 84 Fusion Inhibitors .... 85 Enfuvirtide (ENF, T-20, Pentasufide, Fuzeon) .... 86 Investigational Drugs .... 88 Conclusion .... 89 References .... 90 Chapter 3. General (Non-Antiretroviral) Antiviral Drugs .......................................... 123 Introduction .... 123 Viral Infections Other than HIV .... 126 Herpes Simplex Virus (HSV-1 and -2) .... 126 Varicella Zoster Virus (VZV) .... 131 Epstein-Barr Virus (EBV) .... 132 Cytomegalovirus (CMV) .... 133 Human Herpesvirus 8 (HHV-8) .... 135 Human Papillomavirus (HPV) .... 135 Molluscum Contagiosum Virus (MCV) and other Poxviruses .... 137 Hepatitus B Virus (HBV)/Hepatitus C Virus (HCV) .... 139 Influenza Virus .... 140 Respiratory Syncytial Virus (RSV) .... 142 Rhinovirus .... 142 Nucleoside Analogs .... 143 Acyclovir .... 143 Valacyclovir .... 154 Famciclovir .... 160 Penciclovir .... 166 Ganciclovir .... 169 Valganciclovir .... 174 Ribavirin .... 178 Contents xi Nucleotide Analogs .... 184 Cidofovir .... 184 Adefovir .... 190 Antisense Drugs .... 195 Fomivirsen .... 196 Topical Immune Modulators .... 199 Imiquimod .... 199 Interferon-Alpha and Combinations .... 204 Introduction .... 204 Interferon-Alpha .... 205 PEG-Interferon .... 210 Ribavirin and Interferon-Alpha .... 213 Ion Channel Function Inhibitors of M2 Proteins and Neuraminidase Inhibitors .... 216 Amantadine .... 217 Rimantadine .... 224 Zanamivir .... 226 Oseltamivir .... 230 Pyrimidines .... 235 Trifluridine (1% Ophthalmic Solution) .... 235 Other Antivirals and Medications .... 238 Foscarnet .... 238 Docosonal .... 245 Implications for New Antiviral Agents .... 246 References .... 246 Chapter 4. Vaccines and Immunotherapies ........... 291 Introduction .... 291 Smallpox and Other Poxviruses .... 296 Smallpox .... 296 New Vaccines for Poxviruses Currently Under Investigation .... 300 Measles, Mumps, and Rubella Vaccines .... 300 Measles .... 312 Mumps .... 313 Rubella .... 314 Varicella-Zoster Virus Vaccine .... 315 Influenza Virus Vaccine .... 318 New Developments in Influenza Vaccines .... 321 Hepatitis A Virus Vaccine .... 321 xii Contents Hepatitis B Virus Vaccine .... 323 Rabies Virus Vaccine .... 326 Recent and Continuing Developments in Rabies Vaccines .... 330 Poliovirus Vaccines .... 331 Yellow Fever Virus Vaccine .... 336 Japanese Encephalitis Virus Vaccine .... 339 Adenovirus Vaccines .... 341 Investigational Vaccines .... 342 Rotavirus .... 342 Varicella-Zoster Virus Vaccine .... 345 Human Immunodeficiency Virus Vaccine .... 349 Herpes Simplex Virus Vaccine .... 352 Human Papillomavirus Vaccine .... 354 Cytomegalovirus Vaccine .... 355 Respiratory Syncytial Virus Vaccine .... 357 Parainfluenza Virus Vaccine .... 359 Other Vaccines .... 361 Immunoglobulins .... 362 Monoclonal Antibodies .... 367 Conclusion .... 368 References .... 370 Index .... 409