HIV I: Molecular Biology and Pathogenesis: Clinical Applications: Molecular Biology and Pathogenesis: Clinical Applications
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Table of contents
- Copyright Pageiv
- Contentsv
- Contributorsxv
- Prefacexix
- Chapter 1. HIV Therapeutics: Past, Present, and Future1
- I. Individual Drugs and Their Pharmacology2
- II. Clinical Studies18
- III. Current Recommendations for Treating HIV-1 Infection25
- Chapter 2. HIV Drug Resistance and Viral Fitness41
- I. Introduction41
- II. Methods of Assessment of Viral Fitness45
- III. Resistance to Nucleoside Analogs47
- IV. Resistance to Other Reverse Transcriptase Inhibitors52
- V. Resistance to Protease Inhibitors53
- VI. In Vivo Consequences of Resistance-Associated Loss of HIV Fitness57
- References60
- Chapter 3. Inhibitors of HIV-1 Reverse Transcriptase67
- I. Introduction67
- II. The Target68
- III. Nucleoside Reverse Transcriptase Inhibitors (NRTI)70
- IV. Nonnucleoside HIV-1 RT Inhibitors (NNRTI)84
- V. Conclusions and Future Directions98
- References100
- Chapter 4. HIV-1 Protease: Maturation, Enzyme Specificity, and Drug Resistance111
- I. Introduction111
- II. Organization of the Gag-Pol Precursor and Molecular Structure of the Mature PR112
- III. Mechanism and Regulation of PR Maturation114
- IV. Substrate/Inhibitor Interactions126
- V. Enzyme Specificity128
- VI. Drug Resistance133
- References140
- Chapter 5. HIV-1 Integrase Inhibitors: Past, Present, and Future147
- I. Introduction147
- II. Chemistry of Retroviral Integration149
- III. Role of Divalent Metals: Stoichiometry and Catalysis151
- IV. Inhibitor Development154
- V. Perspectives160
- References161
- Chapter 6. Selection of HIV Replication Inhibitors: Chemistry and Biology167
- I. Introduction167
- II. RNA-Protein Interactions as a Target for Therapeutic Interventions171
- III. TAR RNA Ligands as Tat Antagonists172
- IV. Encoded One-Bead/One-Compound Combinatorial Library Approach in Discovery of HIV Replication Inh182
- V. Ligands for RRE RNA as Inhibitors of Rev-RRE Interactions188
- VI. Summary and Perspectives190
- References191
- Chapter 7. Therapies Directed against the Rev Axis of HIV Autoregulation199
- I. Introduction199
- II. Transdominant Rev Mutants and Modified Rev Proteins201
- III. Antisense Oligonucleotides206
- IV. Antisense RNA209
- V. Ribozymes210
- VI. RRE Decoys213
- VII. Intracellular Antibodies against Rev217
- VIII. Small Molecules Directed against the Rev Axis218
- IX. Therapies against Rev Cofactors218
- X. Rev-Activated Suicide and Antiviral Therapies218
- XI. Miscellaneous Anti-Rev Effects220
- XII. Clinical Trials220
- XIII. Conclusion221
- References221
- Chapter 8. HIV-1 Gene Therapy: Promise for the Future229
- I. Introduction229
- II. HIV-1 Infection and Conventional Pharmaceutical Agents230
- III. Genetic Antivirals to Block HIV-1 Replication233
- IV. Genetic GunsŽ to Deliver Genetic Antivirals242
- V. Animal Model Systems249
- VI. Clinical Trials251
- References252
- Chapter 9. Assessment of HIV Vaccine Development: Past, Present, and Future263
- I. Introduction263
- II. Virus–Host Interaction264
- III. Envelope Glycoprotein267
- IV. Viral Vaccine Strategies274
- V. Progress in AIDS Vaccine Development276
- VI. Factors to Consider in Designing an Envelope-Based Vaccine290
- VII. Concluding Remarks295
- References296
- Chapter 10. HIV-1-Associated Central Nervous System Dysfunction315
- I. Introduction315
- II. HIV-1-Associated CNS Disease316
- III. Cellular Aspects of HIV-1 CNS Infection326
- IV. Chemotherapeutic Treatment of HIVD359
- V. Summary362
- References364
- Chapter 11. Molecular Mechanisms of Human Immunodeficiency Virus Type 1 Mother–Infant Transmission387
- I. Introduction387
- II. Timing of HIV-1 Mother–Infant Transmission389
- III. Factors In.uencing HIV-1 Mother–Infant Transmission391
- IV. Effect of Smoking on HIV-1 Mother–Infant Transmission392
- V. Diagnosis of HIV-1 Infection in Perinatally Infected Infants394
- VI. Immunologic Abnormalities in HIV-1-Infected Infants394
- VII. Clinical Manifestations in HIV-1-Infected Infants395
- VIII. Prevention of HIV-1 Mother–Infant Transmission by Antiretroviral Therapy395
- IX. Pathogenesis of HIV-1 Infection and Disease Progression396
- X. Molecular and Biological Characterization of HIV-1 Involved in Mother-to-Infant Transmission398
- XI. Chemokine Receptors and HIV-1 Mother–Infant Transmission402
- XII. Genetic Analysis of HIV-1 Regions Following Mother-to-Infant Transmission403
- References408
- Chapter 12. Molecular Epidemiology of HIV-1: An Example of Asia417
- I. Introduction417
- II. Countries in the Advanced Stage of the HIV-1 Epidemic419
- III. Countries with a High Potential for Rapid Heterosexual Transmission423
- IV. Countries with Low HIV Prevalence Rates426
- References432
- Chapter 13. Simian Immunodeficiency Virus Infection of Monkeys as a Model System for the Study of AI437
- I. Introduction437
- II. SIV as a Model for Human AIDS441
- III. Viral Load Measurements as a Prognostic Indicator448
- IV. Modulation of Viral Replication by Partially Protective Vaccines458
- V. Antiviral Therapy463
- VI. Summary466
- References467
- Chapter 14. Animal Models for AIDS Pathogenesis479
- I. Introduction479
- II. Primate Lentiviruses Cause AIDS481
- III. SIV Infection of Rhesus Monkeys483
- IV. HIV Infection of Macaques484
- V. SHIV Infection of Macaques487
- VI. HSIV488
- VII. HIV Infection of Chimpanzees489
- VIII. HIV Infection of SCID Mice493
- IX. HIV Infection of Rabbits499
- X. Mice Transgenic for Primate Lentivirus Genes499
- References505
- Index515
- Contents of Previous Volumes527
The cumulative death toll from AIDS has reached 16.3 million individuals, and more than 33 million persons are currently living with HIV-1. Although it is one of the most-widely studied viruses, many mysteries remain about this pathogen. In this comprehensive two-volume set, HIV-1: Molecular Biology and Pathogenesis, leading investigators in HIV research present a timely picture of the molecular mechanisms which guide HIV-1 expression and replication and provide the most current clinical strategies for combating this virus. Twenty-six teams of experts unravel structure-function interactions of HIV-1 with host cells and the resulting pathological consequences, review strategies fo treatment, and describe ongoing progress in developing animal models and prophylactic vaccines.
The two volumes, covering viral mechanisms and clinical applications, respectively, are written by an international collection of AIDS expers from North America, Europe, Australia, and Asia.
Key Features
* Detailed insights into viral packaging, expression, and assembly
* Mechanistic understanding of how HIV interacts with receptors and infects cells
* Delineation of virally encoded regulatory processes unique to HIV
* Clinical Applications:
* An updated review of current chemotherapeutics for HIV
* New concepts in the discovery and design of novel anti-HIV drugs
* The latest developments in HIV-vaccine research
The two volumes, covering viral mechanisms and clinical applications, respectively, are written by an international collection of AIDS expers from North America, Europe, Australia, and Asia.
Key Features
* Detailed insights into viral packaging, expression, and assembly
* Mechanistic understanding of how HIV interacts with receptors and infects cells
* Delineation of virally encoded regulatory processes unique to HIV
* Clinical Applications:
* An updated review of current chemotherapeutics for HIV
* New concepts in the discovery and design of novel anti-HIV drugs
* The latest developments in HIV-vaccine research