Clinical perspectives on human genetic screening to prevent nevirapine toxicity.

TitleClinical perspectives on human genetic screening to prevent nevirapine toxicity.
Publication TypeJournal Article
Year of Publication2012
AuthorsHaas DW, Mootsikapun P, Ruxrungtham K, Podzamczer D
Corporate AuthorsNevirapine Toxicogenomics Study Team
JournalPer Med
Volume9
Issue7
Pagination773-782
Date Published2012 Sep 1
ISSN1741-0541
Abstract

Nevirapine is one of the most extensively prescribed antiretroviral drugs worldwide. However, a concern is increased risk for severe toxicity when antiretroviral-naive individuals with higher CD4 T-cell counts initiate nevirapine-containing regimens. Several genetic variants are associated with nevirapine toxicities. The authors used data from a previous study to anticipate potential consequences of genetic screening to prevent nevirapine adverse events. That study enrolled cohorts of African, Asian and European descent in 11 countries, including 276 patients who had experienced severe cutaneous and/or hepatic adverse events with nevirapine-containing regimens and 587 matched nevirapine-tolerant controls. Associations were identified with HLA-Cw*04, HLA-B*35, HLA-DRB*01 and CYP2B6 516G>T (rs3745274); however, positive predictive values for these genetic markers were low, and most nevirapine-associated adverse events occurred in patients without these markers. Unless better genetic predictors are identified, nevirapine toxicity is best avoided by continuing to follow current prescribing guidelines that are based largely on CD4 T-cell criteria.

DOI10.2217/pme.12.82
Alternate JournalPer Med
PubMed ID23439719
PubMed Central IDPMC3579661
Grant ListR01 AI077505 / AI / NIAID NIH HHS / United States