A magisterial survey of all aspects of the reverse transcriptase inhibitors (RTIs) used to treat HIV/AIDS, including drug discovery, pharmacology, development of drug resistance, toxicity, and prevention of mother-to-child transmission of HIV/AIDS. The authors synthesize our current understanding of the role of reverse transcriptase in the viral life cycle, describe the discovery and development of eight nucleoside and nucleotide analogs that represent milestones in treatment history, and thoroughly discuss the question of toxicity and resistance to this class of drugs. They also address three non-nucleoside RTIs and their pharmacokinetics and comparative clinical efficacy, new RTIs currently under development, and the impact of approved agents on treatment, in general, and on vertical transmission in the developing world.
Inhoudsopgave
Structural Studies on HIV Reverse Transcriptase Related to Drug Discovery.- Zidovudine, Lamivudine, and Abacavir.- Stavudine, Didanosine, and Zalcitabine.- Emtricitabine.- Nucleotide Analogs.- Resistance to Nucleoside and Nucleotide Reverse Transcriptase Inhibitors.- Pharmacokinetics of Reverse Transcriptase Inhibitors.- Peripheral Neuropathy Associated With Nucleoside Reverse Transcriptase Inhibitor Therapy.- Mitochondrial Dysfunction and Nucleoside Reverse Transcriptase Inhibitor Therapy.- Mitochondrial Toxicity and Lipodystrophy.- Nevirapine.- Efavirenz.- Delavirdine.- Resistance to Non-Nucleoside Reverse Transcriptase Inhibitors.- Vertical Transmission of HIV and Therapeutic Interventions.- New Reverse Transcriptase Inhibitors in Development.- Antiretroviral Drugs for Millions.
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