Antiretroviral Therapy for HIV: Pharmacogenetic Considerations

Pharmacists can expect to see considerably more information about the implications of pharmacogenetics for drug treatment in every disease state. One disease state that has traditionally been challenging is that of antiretroviral therapy (ART) for patients with HIV. We now know that human genome sequence variations can have a profound effect on patients' antiviral therapy.

The journal Expert Opinion in Drug Metabolism and Toxicology has published a new article that discusses specific pharmacogenetic considerations in the HIV patient. This review article was assembled by a group of researchers from the University of Liverpool in Liverpool, UK.

The researchers focused on ethnicity, environment, and culture as influences on single nucleotide polymorphisms (SNP). SNPs may result from deletion, insertion, or substitution of a single nucleotide in a gene. SNPs that cause different amino acids or premature stop codons are called non-synonymous, and may be of pharmacologic relevance.

Research has now been able to identify SNPs that affect ART pharmacokinetics, efficacy, and toxicity.

Individuals from different ethnicities are prone to having genetic polymorphisms pursuant to migration, colonization events, and population expansion or decline over thousands of years. Some populations have very little genetic diversity while others have a considerable amount of genetic diversity. A person's ancestry, environment, or cultural upbringing can affect drug efficacy.

Most pharmacists are aware that patients who carry the HLA-B*57—01 allele are at significantly increased risk of abacavir hypersensitivity. Patients who carry this gene are likely to develop fever, rash, gastrointestinal discomfort, fatigue, cough, and shortness of breath. For this reason, screening for this gene before initiating abacavir is recommended.

The authors also covered other polymorphisms that affect ART. Specifically, they examined CYP2B6, CYP3A, and CYP2D, as well as phase 2 metabolism and transporters that are key to absorption, distribution, metabolism, and excretion of drugs.

The researchers emphasized more collaboration between professionals in different disciplines and urged more study to examine how environmental and cultural differences affect individual response to ART. They urged clinicians to prepare for the reality of providing good care for patients with HIV using pharmacogenetics/pharmacogenomics information.

Reference

Neary M, Owen A. Pharmacogenetic considerations for HIV treatment in different ethnicities: an update. Expert Opin Drug Metab Toxicol. 2017 Oct 16:1-13. doi: 10.1080/17425255.2017.1391214. [Epub ahead of print]