Resistance to antiretroviral therapy

• Published in: Farmacia hospitalaria Vol. 28; no. 6 Suppl 1; pp. 55 - 71
• Main Authors: Alberdi Leniz, A, Tuset Creus, M, Martín Conde, M, del Cacho del Cacho, E, Nigorra Caro, M, Codina Jané, C, Ribas I Sala, J
• Format: Journal Article
• Language: Spanish
• Published: Spain 2004
• Subjects: Anti-Retroviral Agents - therapeutic use; Drug Resistance, Viral; HIV Infections - drug therapy; Humans
• ISSN: 1130-6343

After some time under treatment, HIV+ patients have a virologic failure rate of 50%, being development of resistance to therapy responsible for up to 80% of the virologic failure. In addition, resistance rates in naive patients is around 10% in developed countries. Inherent characteristics of HIV (replication cycle, viral subtype), of patients (therapy compliance, intra-/interindividual variability, genetic polymorphisms), and of therapy (genetic barrier to drug resistance, inhibitory ratio, drug interactions) are the factors involved in the development of resistance, and their interpretation requires to be studied. Resistance identification will be carried out using genotypical and/or phenotypical methods, and their adequacy has been validated by various expert panels on resistance. The role of the pharmacokinetic and pharmacodynamic monitoring of antiretroviral therapy is also crucial within the field of resistance, and concerns us directly as pharmacists. Finally, understanding the resistance patterns of currently available or experimental antiretroviral drug families will provide the necessary tools to prevent and/or manage their development. To know and understand the mechanisms and patterns of resistance for each antiretroviral family. To identify factors involved in the development of resistance to ART, and to interpret various resistance tests. Studies were identified using Medline, the Cochrane database of systemic reviews, abstracts from international meetings on AIDS, Conference on Retroviruses and Opportunistic Infections, international meetings on resistance to antiretrovirals, and product monographs from January 1999 to February 2004. To be eligible, studies had to describe viral genome mutations responsible for resistance or hypersusceptibility to ART in relation to precipitating factors. Papers describing resistance identification techniques were also selected. In all, 1,083 full articles and 64 abstracts and communications at international meetings were retrieved, of which 74 articles and 20 abstracts met the inclusion criteria for our review. Of the 94 reports selected, 86 discussed factors involved in the development of resistance and resistance test interpretation. The remaining 8 reports focused on resistance patterns to the various antiretroviral drug families. Every article described the enzymatic mechanisms induced by mutations responsible for resistance or hypersusceptibility to each antiretroviral family, the classification and nomenclature for each mutation, and the influence of each mutation on the success or failure of patient treatment. REVIEWER S CONCLUSIONS: Knowledge of the mechanisms and patterns of resistance to each antiretroviral family will allow us to overall understand the evolution and outcome of treatment for any given patient. Only thus shall we be able to play an integral role in the therapy of patients.