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Pharmacogenetics of Efavirenz Discontinuation for Reported CNS Symptoms

ABSTRACT:

This is an evaluation of genetic associations with efavirenz (EFV) discontinuation for central nervous system (CNS) symptoms within 12 months of treatment. Patients were treated at an HIV primary care clinic in Nashville TN from 1998 to 2012. Previously known SNPs in CYP2B6 and CYP2A6 were used to define metabolizer genotypes (extensive, intermediate, slow metabolizer). Over 500,000 SNPs from genome-wide genotyping were used to define MDS (Multidimensional Scaling) coordinates to account for population stratification. Patients were defined as cases if they discontinued EFV for CNS symptoms within 12 months, otherwise they were defined as controls if they did not stop treatment.

Among 563 evaluable participants, the hazard ratio for EFV discontinuation for CNS symptoms was 4.9 (95% C.I. 1.9 TO 12.4, p=0.001) in slow metabolizers compared to extensive metabolizers. This association was very significant in Whites 6.5 (95% CI: 2.3 to 18.8; p = 0.001), but not in Blacks 2.6 (95% C.I. 0.5 to 14.1; p = 0.27). The reason for this difference by race is not clear and warrants further investigation.

PROVIDER: phs001253 | dbGaP |

SECONDARY ACCESSION(S): PRJNA354669PRJNA354670

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs001253.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001253.EfavirenzCNS_SideEffects.v1.p1.MULTI.pdf	Pdf
	manifest_phs001253.EfavirenzCNS_SideEffects.v1.p1.c1.DS-HIV-IRB.pdf	Pdf
	datadict_v2.xsl	Other

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