Clinical perspectives on human genetic screening to prevent nevirapine toxicity

Nevirapineis 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 nevirapinetoxicities. The authors used data from a previous study to anticipate potential consequences of genetic screeningto prevent nevirapineadverse 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 CYP2B6516G>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, nevirapinetoxicity is best avoided by continuing to follow current prescribing guidelines that are based largely on CD4 T-cell criteria.