ID

45692

Descrizione

Principal Investigator: David W. Haas, MD, Vanderbilt University School of Medicine, Nashville, Tennessee, USA MeSH: Central Nervous System Diseases,Dizziness,Insomnia,Hallucinations,Headache https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001253 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.

collegamento

dbGaP study = phs001253

Keywords

  1. 08/05/23 08/05/23 - Simon Heim
Titolare del copyright

David W. Haas, MD, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

Caricato su

8 maggio 2023

DOI

Per favore, per richiedere un accesso.

Licenza

Creative Commons BY 4.0

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dbGaP phs001253 Pharmacogenetics of Efavirenz Discontinuation for Reported CNS Symptoms

Eligibility Criteria

Inclusion and exclusion criteria
Descrizione

Inclusion and exclusion criteria

Alias
UMLS CUI [1,1]
C1512693
UMLS CUI [1,2]
C0680251
*Inclusion Criteria*
Descrizione

*Inclusion Criteria*

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C1512693
HIV-infected patients
Descrizione

HIV-infected patients

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C0019693
ART naÏve patients who Initiated EFV-containing ART regimens during clinical care at Vanderbilt Comprehensive Care Center in Nashville, TN from 1998 to 2012.
Descrizione

ART naÏve patients who Initiated EFV-containing ART regimens during clinical care at Vanderbilt Comprehensive Care Center in Nashville, TN from 1998 to 2012.

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C1963724
UMLS CUI [1,2]
C0332256
UMLS CUI [1,3]
C0674428
UMLS CUI [1,4]
C1963724
UMLS CUI [1,5]
C1947933
UMLS CUI [1,6]
C1552443
Patients who had at least one follow-up visit after ART initiation visit.
Descrizione

Patients who had at least one follow-up visit after ART initiation visit.

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C0589121
UMLS CUI [1,2]
C1963724
Patients who provided written informed consent for genetic testing through the CFAR Data and Specimen Repository.
Descrizione

Patients who provided written informed consent for genetic testing through the CFAR Data and Specimen Repository.

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C0021430
UMLS CUI [1,2]
C1320549
UMLS CUI [1,3]
C1541218
UMLS CUI [1,4]
C3847505
Patients who had genotype data in *CYP2B6*, *CYP2A6* and whole genome exome data.
Descrizione

Patients who had genotype data in *CYP2B6*, *CYP2A6* and whole genome exome data.

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C0017431
UMLS CUI [1,2]
C1382176
UMLS CUI [1,3]
C1413868
UMLS CUI [1,4]
C5446360
*Exclusion Criteria*
Descrizione

*Exclusion Criteria*

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C0680251
Initiated the EFV-containing regimen during participation in an ACTG clinical trial.
Descrizione

Initiated the EFV-containing regimen during participation in an ACTG clinical trial.

Tipo di dati

boolean

Alias
UMLS CUI [1,1]
C0674428
UMLS CUI [1,2]
C1276413
UMLS CUI [1,3]
C0008976

Similar models

Eligibility Criteria

Name
genere
Description | Question | Decode (Coded Value)
Tipo di dati
Alias
Item Group
Inclusion and exclusion criteria
C1512693 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
*Inclusion Criteria*
Item
*Inclusion Criteria*
boolean
C1512693 (UMLS CUI [1,1])
HIV-infected patients
Item
HIV-infected patients
boolean
C0019693 (UMLS CUI [1,1])
ART naÏve patients who Initiated EFV-containing ART regimens during clinical care at Vanderbilt Comprehensive Care Center in Nashville, TN from 1998 to 2012.
Item
ART naÏve patients who Initiated EFV-containing ART regimens during clinical care at Vanderbilt Comprehensive Care Center in Nashville, TN from 1998 to 2012.
boolean
C1963724 (UMLS CUI [1,1])
C0332256 (UMLS CUI [1,2])
C0674428 (UMLS CUI [1,3])
C1963724 (UMLS CUI [1,4])
C1947933 (UMLS CUI [1,5])
C1552443 (UMLS CUI [1,6])
Patients who had at least one follow-up visit after ART initiation visit.
Item
Patients who had at least one follow-up visit after ART initiation visit.
boolean
C0589121 (UMLS CUI [1,1])
C1963724 (UMLS CUI [1,2])
Patients who provided written informed consent for genetic testing through the CFAR Data and Specimen Repository.
Item
Patients who provided written informed consent for genetic testing through the CFAR Data and Specimen Repository.
boolean
C0021430 (UMLS CUI [1,1])
C1320549 (UMLS CUI [1,2])
C1541218 (UMLS CUI [1,3])
C3847505 (UMLS CUI [1,4])
Patients who had genotype data in *CYP2B6*, *CYP2A6* and whole genome exome data.
Item
Patients who had genotype data in *CYP2B6*, *CYP2A6* and whole genome exome data.
boolean
C0017431 (UMLS CUI [1,1])
C1382176 (UMLS CUI [1,2])
C1413868 (UMLS CUI [1,3])
C5446360 (UMLS CUI [1,4])
*Exclusion Criteria*
Item
*Exclusion Criteria*
boolean
C0680251 (UMLS CUI [1,1])
Initiated the EFV-containing regimen during participation in an ACTG clinical trial.
Item
Initiated the EFV-containing regimen during participation in an ACTG clinical trial.
boolean
C0674428 (UMLS CUI [1,1])
C1276413 (UMLS CUI [1,2])
C0008976 (UMLS CUI [1,3])

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