TY - JOUR
T1 - Virologic correlates of adherence to antiretroviral medications and therapeutic failure
AU - Perno, Carlo Federico
AU - Ceccherini-Silberstein, Francesca
AU - De Luca, Andrea
AU - Cozzi-Lepri, Alessandro
AU - Gori, Caterina
AU - Cingolani, Antonella
AU - Bellocchi, Maria Concetta
AU - Trotta, Maria Paola
AU - Piano, Paola
AU - Forbici, Federica
AU - Scasso, Antonio
AU - Vullo, Vincenzo
AU - D'Arminio Monforte, Antonella
AU - Antinori, Andrea
PY - 2002/12/15
Y1 - 2002/12/15
N2 - 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.
AB - 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.
KW - Adherence
KW - Antivirals
KW - Fitness
KW - HIV
KW - Mutations
KW - Reservoirs
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M3 - Article
C2 - 12562033
AN - SCOPUS:0037114847
SN - 1525-4135
VL - 31
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - SUPPL. 3
ER -