Incorporating antiretroviral resistance testing into clinical practice

An explanation of why knowing when and how to use resistance testing in clinical practice will lead to better clinical management of HIV-1-infected patients.

Antiretroviral resistance due to viral gene mutations accounts for a large portion of treatment failures. The emergence of these genetic changes in the human immunodeficiency virus type 1 (HIV-1) is fostered by ongoing viral replication in the presence of subinhibitory concentrations of antiretrovirals. Poor penetration of drugs into certain bodily compartments (sanctuary sites), inadequate adherence, and variable pharmacokinetic factors may contribute to subtherapeutic drug levels in vivo. This, in turn, may allow for selection of either preexisting (archived) or newly generated drug-resistant mutants. The critical problem in the clinical setting is that a mutant selected for by a failing regimen may have some degree of cross-resistance to other drugs in the same class that have not yet been prescribed to that patient. The development of cross-resistance may lead to a reduced virologic or immunologic response to subsequent regimens. As scientists develop new agents active against resistant virus, clinical medicine is also implementing diagnostic strategies designed to detect antiretroviral resistance and individualise subsequent regimens.

Identification of the presence of drug resistance by means of genotypic or phenotypic resistance assays can help a healthcare provider select a combination of antiretrovirals that is likely to suppress HIV-1 replication (ie, “active drugs” to which that patient’s virus population is not cross-resistant). To maximise the therapeutic benefit and minimise toxicity, information collected from the viral genotype or phenotype must be used in conjunction with the patient’s antiretroviral treatment history, response to past regimens, immunologic status, pharmacologic data, and the clinician’s own knowledge of antiretroviral drugs. Knowing when and how to use resistance testing in a clinical practice will lead to better clinical management of HIV-1-infected patients.