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Expert Opinion on Investigational Drugs Volume 13, 2004 - Issue 8
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Review

Understanding HIV resistance, fitness, replication capacity and compensation: targeting viral fitness as a therapeutic strategy

Robert W Buckheit Jr ImQuest BioSciences, Inc., 7340 Executive Way, Suite R, Frederick, Maryland 21704, USA. [email protected]
Pages 933-958 | Published online: 24 Feb 2005

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  • •An excellent review chapter on therapy for HIV infection.
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  • •An excellent overview of mutations that engender resistance to the NNRTIs.
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  • •An excellent overview of mutations that engender resistance to the protease inhibitors.
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  • •An excellent overview of mutations that engender resistance to the NRTIs.
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  • •An excellent overview of mutations that engender resistance to the NNRTIs.
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  • •An excellent review of toxicities observed to the various anti-HIV agents.
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  • ••An essential review for issues involvingHIV resistance and fitness.
  • SUFKA SA, FERRARI G, VE et al.: Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control../. Infect. Dis. (2003) 187:1027–1037.
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  • •A discussion of the effects of the Met184Val mutation in the RT.
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  • •Mechanistic evaluation of the effect of Met184Val on enhancing sensitivity of AZT-resistant strains to AZT.
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  • •A report on the effects of two NRTI resistance-engendering mutations on viral fitness.
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  • ••An informative study of the potential forlocking deleterious resistance and fitness changes into the genome.
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  • ••A review of NNRTI resistance and fitness,describing a competitive fitness assay.
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  • •Methodology and issues of resistance selection assays.
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  • •Methodology and issues of resistance selection assays.
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  • •Example of resistance selection requiring multiple amino acid changes to achieve high level resistance to an NNRTI.
  • BUCKHEIT RW Jr, WHITE EL, FLIAKAS-BOLTZ V et al: Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide. Antimicrob. Agents Chemother. (1999) 43:1827–1834.
  • •Example of multiple NNRTI resistance selection strategy yielding multi-drug resistance.
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  • •Presentation of methods that are important with regard to selecting drug-resistant viruses.
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  • •An excellent summary updated annually on resistance mutations in all HIV genes and for all classes of antiviral agents.
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  • •Effects of therapy discontinuation on resistant variants in patients.
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  • •Effects of therapy discontinuation on resistant variants in patients.
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  • •Effects of therapy discontinuation on resistant variants in patients.
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  • •Effects of therapy discontinuation on resistant variants in patients.
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  • ••An excellent paper on the evolution ofNNRTI resistance and fitness during therapy.
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  • •Fitness of clinical virus strains prior to selection found to be lower than wild-type NL4–3.
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  • DAUBER DS, ZIERMANN R, PARKIN N et al.: Altered substrate specificity of drug-resistant human immunodeficiency virus type 1 protease.
  • •Virol (2002) 76:1359–1368.
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  • •Virol (1996) 70:3763–3769.
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  • •First report of the fitness effects of T20-resistant virus mutations.
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  • FIKKERTV, VAN MAELE B, J et al.: Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. J. Virol (2003) 77:11459–11470.
  • •Report on resistance to DKA integrase inhibitors.
  • YOSHINAGA AS, T F et al.: IX Conference on Remowiuses and Opportunistic Infections Brasilia, Brazil (2002).
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  • ••Excellent discussion of dade effects onsensitivity to drugs and resistance.
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  • •Excellent discussion of subgroup 0 viruses.
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  • LOEMBA H, BRENNER B, MA et al.: Polymorphisms of cytotoxic T-lymphocyte (CTL) and T-helper epitopes within reverse transcriptase (RT) of HIV-1 subtype C from Ethiopia and Botswana following selection of antiretroviral drug resistance. Anti viral Res. (2002) 56:129–142.
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  • ••Excellent recent review on viral fitness.
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  • ••Review on viral fitness.
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  • ••Review on viral fitness.
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  • ••Excellent recent review on viral fitness.
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  • ••Excellent recent review on viral fitness.
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Websites

  • http://www.aidsinfo.nih.gov/drugs/ current information on approved and experimental anti-HIV agents.

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