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Interpretation of HIV drug resistance testing

Author
Michael J Kozal, MD
Section Editors
Martin S Hirsch, MD
Paul E Sax, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

With improvements in the efficacy, safety, tolerability, and convenience of antiretroviral therapy (ART), preventing and managing antiretroviral drug resistance has become less challenging than it was in the past. Nevertheless, clinicians caring for HIV-infected patients need to understand the resistance patterns associated with specific antiretroviral medications so that they may appropriately select treatment regimens that will maximize the likelihood of viral suppression [1]. While these patterns can be complex, there are basic principles that underlie effective utilization of resistance data, particularly when making decisions about switching drug regimens after virologic failure.

This topic will address the major resistance patterns found in association with different antiretroviral agents and how that knowledge impacts the selection of an appropriate treatment regimen. The details in this topic refer mainly to resistance patterns seen with HIV subtype B, which is the most prevalent clade in the United States, Europe, Japan, Thailand, and Australia. (See "Global epidemiology of HIV infection".)

Topic reviews that discuss the different types of resistance tests, as well as the selection of antiretroviral therapy regimens, are found elsewhere. (See "Overview of HIV drug resistance testing assays" and "Evaluation of the treatment-experienced patient failing HIV therapy" and "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "Selecting an antiretroviral regimen for treatment-experienced HIV-infected patients who are failing therapy" and "Treatment of HIV-2 infection".)

FACTORS CONTRIBUTING TO RESISTANCE

Multiple factors influence the development of HIV drug resistance, including the biology of HIV, genetic barriers to resistance, regimen potency, pharmacokinetics of antiretroviral drugs, and medication adherence. Drug-resistant mutations can predate the initiation of a specific drug regimen or can develop when viral replication continues in the face of ongoing drug pressure.

HIV biology – HIV infection is characterized by high rates of replication, with more than 109 virions produced daily [2]. In addition, HIV reverse transcriptase, which is responsible for replicating the viral genome, is error-prone. The combination of the high rate of replication and the frequent introduction of mutations during each round of replication leads to the occurrence of randomly generated mutations, some of which confer drug resistance [3]. The resulting population of genetically related, but distinct, HIV variants in a patient is referred to as a "quasispecies."

                                    
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Literature review current through: Sep 2017. | This topic last updated: Sep 29, 2017.
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