[Resistance to integrase inhibitors].

Abstract

Integrase inhibitors are the most recently approved family of antiretroviral agents for the treatment of HIV infection. As with other antiretroviral agents, under pharmacological pressure, the virus selects resistance mutations if viral suppression is incomplete. Mutations are selected in the integrase gene, specifically in positions proximal to the catalytic center. Because clinical experience with these drugs is scarce, information on resistance is limited. Virologic failure with raltegravir is associated with selection of primary mutations such as N155H (40%) and distinct changes in position Q148 (28%). Less frequently, Y143R (6.6%) and E92Q are selected. The most frequently observed mutations in failure with elvitegravir are E92Q, E138K, Q148R/K/H and N155H, and less frequently S147G and T66A/I/K. The most common resistance pattern seems to be E138K + E147G + Q148R. There is a high grade of cross resistance between raltegravir and elvitegravir, making sequencing between these two drugs impossible.

• Authors: Carolina Garrido, Carmen de Mendoza, Vicente Soriano
• Journal: Enfermedades infecciosas y microbiologia clinica (Enferm Infecc Microbiol Clin) Vol. 26 Suppl 12 Pg. 40-6 (Nov 2008) ISSN: 0213-005X [Print] Spain
• Vernacular Title: Resistencia a los inhibidores de la integrasa.
• PMID: 19572425 (Publication Type: Journal Article, Review)

Chemical References

• HIV Integrase Inhibitors
• Pyrrolidinones
• Quinolones
• Raltegravir Potassium
• elvitegravir
• HIV Integrase

Topics

• Amino Acid Substitution
• Clinical Trials as Topic
• Drug Resistance, Multiple, Viral (genetics)
• Drug Resistance, Viral (genetics)
• Genetic Variation
• HIV (drug effects, enzymology, genetics)
• HIV Infections (drug therapy)
• HIV Integrase (chemistry, drug effects, genetics)
• HIV Integrase Inhibitors (pharmacology, therapeutic use)
• Humans
• Models, Molecular
• Mutation, Missense
• Point Mutation
• Protein Conformation
• Pyrrolidinones (pharmacology, therapeutic use)
• Quinolones (pharmacology, therapeutic use)
• Raltegravir Potassium