Virologic correlates of adherence to antiretroviral medications and therapeutic failure.
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.
Perno
Carlo Federico
CF
INMI L Spallanzani, Rome, Italy. cf.perno@uniroma2.it
Ceccherini-Silberstein
Francesca
F
De Luca
Andrea
A
Cozzi-Lepri
Alessandro
A
Gori
Caterina
C
Cingolani
Antonella
A
Bellocchi
Maria Concetta
MC
Trotta
Maria Paola
MP
Piano
Paola
P
Forbici
Federica
F
Scasso
Antonio
A
Vullo
Vincenzo
V
d'Arminio Monforte
Antonella
A
Antinori
Andrea
A
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D006801:Humans; D010349:Patient Compliance; D017211:Treatment Failure; D014779:Virus Replication
D019380:Anti-HIV Agents