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Antiretroviral Resistance in Clinical Practice
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Antiretroviral Resistance in Clinical Practice
Gerretti
Anna Maria
2006
© 2006
Mediscript Ltd.
Table of Contents
Contributors
Introduction
Chapter 1 Resistance to nucleoside reverse transcriptase inhibitors
Anne-Geneviève Marcelin
Introduction
Mechanisms of NRTI resistance
NRTI-associated resistance mutations
Conclusion
Recommendations for clinical practice
References
Chapter 2 Resistance to non-nucleoside reverse transcriptase inhibitors
Nicola Mackie
Introduction
Patterns of resistance mutations
Mutations and pathways conferring resistance to NNRTIs
Transmission of resistance and persistence of mutations
Stopping NNRTI therapy
Continuing NNRTI therapy in the presence of resistance
NNRTI hypersusceptibility
Investigational NNRTIs
Recommendations for clinical practice
References
Chapter 3 Resistance to protease inhibitors
Noortje van Maarseveen and Charles Boucher
HIV-1 protease
HIV-1 protease inhibitors
Resistance mutations
Changes in replicative capacity
High genetic barrier to protease inhibitors and boosted protease inhibitors
Conclusion
Recommendations for clinical practice
References
Chapter 4 Resistance to entry inhibitors
Eva Poveda and Vincent Soriano
Introduction
Resistance to CD4–gp120 binding inhibitors
Resistance to CCR5 and CXCR4 antagonists
Resistance to fusion inhibitors
Conclusions
References
Chapter 5 Resistance assays
Martin Schutten
Introduction
Phenotyping assays
Genotyping assays
Virtual phenotyping assays
Conclusions
Recommendations for clinical practice
References
Chapter 6 Interpretation algorithms
Tobias Sing and Martin Däumer
Introduction: selection of antiretroviral therapy
The factors of interest: drug activity, viral phenotype and virological response
Predicting in vivo antiviral activity of individual drugs
Predicting
in vitro
resistance and replication capacity from the viral genotype
Predicting in vivo virological response to combination therapy
Summary
The future
Recommendations for clinical practice
Acknowledgments
References
Chapter 7 Clinical cut-offs in the interpretation of phenotypic resistance
Carlo-Federico Perno and Ada Bertoli
Introduction
Definition of cut-off for the interpretation of resistance assays
Genotypic assays
Recommendations for clinical practice
References
Chapter 8 Pharmacokinetic implications of resistance
Marta Boffito
Introduction
Pharmacokinetics of antiretroviral agents
Therapeutic drug monitoring
The inhibitory quotient
Conclusion
Recommendations for clinical practice
Acknowledgement
References
Chapter 9 Benefits of resistance testing
Diane Descamps and Françoise Brun-Vézinet
Introduction
Prospective resistance trials: evidence for resistance testing
Therapeutic trials: evidence for resistance testing
Benefit of resistance testing in drug-naive patients
Conclusion
Recommendations for clinical practice
References
Chapter 10 Transmitted resistance
Clare Booth
Definition of primary resistance
Transmission of drug-resistant mutants
Persistence of transmitted drug-resistant mutants
Detection of minority transmitted drug-resistant mutants
Compartmentalisation of drug-resistant virus and potential for transmission
Current guidelines on resistance testing in drug-naive patients
The potential impact of superinfection on resistance patterns of drug-naive patients
Epidemiology of primary resistance
Impact of primary resistance on treatment responses
Conclusions
Recommendations for clinical practice
References
Chapter 11 The significance of minority drug-resistant quasispecies
Karin Metzner
Introduction
The heterogeneity of HIV-1
Persistent infection: latency and residual replication
Detection and quantification of minority quasispecies of drug-resistant HIV-1
Persistence of drug-resistant viral variants
Impact of minority quasispecies of drug-resistant HIV-1 on the outcome of antiretroviral therapy
Conclusion and future perspectives
Recommendations for clinical practice
Acknowledgements
References
Chapter 12 The impact of resistance on viral fitness and its clinical implications
Andrea De Luca
Introduction
Definition of HIV-1 fitness
Methods to determine HIV-1 fitness
Genotypic drug resistance and viral fitness
Nucleoside reverse transcriptase inhibitor-resistant mutations
Non-nucleoside reverse transcriptase inhibitor-resistant mutations
Protease inhibitor-resistant mutations
Glycoprotein gp41 resistance mutations
Viral fitness and therapeutic response: potential clinical applications
Conclusions
Recommendations for clinical practice
References
Chapter 13 The significance of subtype-related genetic variability: controversies and unanswered questions
Ricardo Camacho
Introduction
Current knowledge
Subtype-specific mutations
Influence of subtypes on the pathways of antiretroviral drug resistance
Reliability of phenotypic and genotypic assay results for evaluating resistance in non-B subtypes
Entry inhibitors
Conclusions
Recommendations for clinical practice
References
Chapter 14 Database analyses of predictors of resistance
Caroline Sabin
Introduction
Study designs for identifying predictors of resistance
Analytical issues
Eliminating other causes of bias: interpreting trends over time
Recommendations for clinical practice
References
Chapter 15 Understanding the statistical analysis of resistance data
Alessandro Cozzi-Lepri
Introduction: nature of the data
Data managing: the choice of reference HIV-1 strain
Common assumptions: the importance of basic knowledge of HIV-1 virology
Programming interpretation rules and choice of a suitable virological endpoint
Possibility of spurious associations
Recommendations for clinical practice
References
Chapter 16 Case studies
Case study 1: Development of resistance on first-line therapy
Case study 2: Evolution of resistance during therapy with ritonavir-boosted protease inhibitors
Case study 3: Reluctance to take antiretroviral therapy
Case study 4: A child with uncertain treatment history and extensive drug resistance
Case study 5: Unrecognised transmitted resistance
Case study 6: A case of persistent low-level viraemia
Case study 7: A young black African woman presenting for HIV testing
List of Figures
Copyright © 2006
Mediscript Ltd.
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