By Gail Skowron, Richard Ogden
A magisterial survey of all features of the opposite transcriptase inhibitors (RTIs) used to regard HIV/AIDS, together with drug discovery, pharmacology, improvement of drug resistance, toxicity, and prevention of mother-to-child transmission of HIV/AIDS. The authors synthesize our present figuring out of the position of opposite transcriptase within the viral existence cycle, describe the invention and improvement of 8 nucleoside and nucleotide analogs that symbolize milestones in remedy background, and carefully speak about the query of toxicity and resistance to this classification of substances. in addition they handle 3 non-nucleoside RTIs and their pharmacokinetics and comparative scientific efficacy, new RTIs presently lower than improvement, and the influence of licensed brokers on therapy, generally, and on vertical transmission within the constructing international.
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Extra resources for Reverse Transcriptase Inhibitors in HIV AIDS Therapy (Infectious Disease)
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78. Silvestri R, Artico M, De Martino G, et al. Synthesis, biological evaluation, and binding mode of novel 1-[2-(diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles targeted at the HIV-1 reverse transcriptase. J Med Chem 2002;45(8):1567–1576. 79. Vig P, Mao C, Venkatachalam TK, Tuel-Ahlgren L, Sudbeck EA, Uckun FM. Rational design and synthesis of phenethyl-5-bromopyridyl thiourea derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase. Bioorg Med Chem 1998;6:1789–1797. 80. Hopkins AL, Ren J, Tanaka H, et al.
It is clear that structural studies of HIV RT do not provide an easy answer to the design of novel anti-AIDS drugs to target virus resistant to current therapies. Nevertheless, the combination of compound screening, virology, and medicinal chemistry together with structure-based design and protein crystallography to test predicted ligand-binding modes brings together a powerful set of tools for developing new HIV RT inhibitors. Such multifaceted approaches are likely to provide the greatest hope of discovering novel anti-RT drugs that will be useful in combating the ever-present threat of drug-resistant HIV.
The use of ZDV in asymptomatic or symptomatic patients with CD4 cell counts greater than 500 cells/mm3 was approved in March 1990. ZDV was initially approved as a monotherapy. Subsequently, ZDV was approved for use in combination regimens with zalcitabine and lamivudine (3TC, Epivir®). Although early studies demonstrated clinical and survival benefits of ZDV alone or in combination with other nucleoside analogs, these benefits were of limited durability because of incomplete virological suppression and the emergence of resistant HIV strains.