Virologic correlates of adherence to antiretroviral medications and therapeutic failure

Carlo Federico Perno, Francesca Ceccherini-Silberstein, Andrea De Luca, Alessandro Cozzi-Lepri, Caterina Gori, Antonella Cingolani, Maria Concetta Bellocchi, Maria Paola Trotta, Paola Piano, Federica Forbici, Antonio Scasso, Vincenzo Vullo, Antonella D'Arminio Monforte, Andrea Antinori

Research output: Contribution to journalArticle

Abstract

Adherence to antiretroviral therapy affects the pharmacokinetics of antiviral drugs and activates a cascade of events ultimately leading to therapeutic success or failure. An optimal adherence usually affords minimal rounds of virus replication and rare spontaneous mutations, which are unable to be fixed in the genome because of the competition of wild-type (more fit) strains. Therefore, adherence-based therapeutic success is mostly accompanied by the prevalence of wild-type strains. In case of poor adherence, virus replication is substantial, and mutations randomly occurring tend to be fixed within the genome. Under these conditions, mutated-resistant strains will outgrow wild-type virus (sensitive to antivirals and thereby unable to compete enough with resistant strains for cellular targets): thus, therapeutic failure occurs, and mutated resistant strains are predominant. In the case of very low or absent adherence, virologic failure occurs, although wild-type virus (whose replication is not significantly affected by antivirals) is not outgrown by mutated strains randomly produced but unable to be fixed within the genome. Taken together, these events and their consequences strongly support the relevance of a tight and continuous monitoring of adherence to antiretroviral drugs to prevent the risk of development of mutated strains often cross-resistant to the majority of antiretroviral drugs currently available.

Original languageEnglish
JournalJournal of Acquired Immune Deficiency Syndromes
Volume31
Issue numberSUPPL. 3
Publication statusPublished - Dec 15 2002

Keywords

  • Adherence
  • Antivirals
  • Fitness
  • HIV
  • Mutations
  • Reservoirs

ASJC Scopus subject areas

  • Immunology
  • Virology

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  • Cite this

    Perno, C. F., Ceccherini-Silberstein, F., De Luca, A., Cozzi-Lepri, A., Gori, C., Cingolani, A., Bellocchi, M. C., Trotta, M. P., Piano, P., Forbici, F., Scasso, A., Vullo, V., D'Arminio Monforte, A., & Antinori, A. (2002). Virologic correlates of adherence to antiretroviral medications and therapeutic failure. Journal of Acquired Immune Deficiency Syndromes, 31(SUPPL. 3).