The Journal of antimicrobial chemotherapy · 2014
Functional CYP2B6 variants and virologic response to an efavirenz-containing regimen in Port-au-Prince, Haiti.
Клиническое исследованиеСтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Haas David W, Severe Patrice, Jean Juste Marc Antoine, Pape Jean William, Fitzgerald Daniel W
Аннотация
OBJECTIVES: Efavirenz is widely prescribed for HIV-1 infection. Three polymorphisms in CYP2B6 define plasma efavirenz trough concentration strata that vary across an ∼10-fold range. We characterized associations between human genetic polymorphisms and virologic response among participants who received efavirenz-containing regimens in a prospective clinical trial.
METHODS: We genotyped 76 polymorphisms in CYP2B6 (including those that define efavirenz concentration strata), CYP2A6, CYP3A4, CYP3A5 and ABCB1 and week 48 virologic responses in 360 Haitians who initiated efavirenz-containing regimens in protocol HT 001. Associations were characterized by logistic regression analysis and Fisher's exact test.
RESULTS: Proportions with HIV-1 RNA <50 or <200 copies/mL did not differ across 10 CYP2B6 metabolizer strata. In analyses that combined strata into three metabolizer levels (extensive, intermediate and slow), the respective proportions were 0.79, 0.79 and 0.81 (<50 copies/mL cut-off) and 0.84, 0.86 and 0.87 (<200 copies/mL cut-off). Genetic associations were not identified after controlling for baseline variables or with other polymorphisms after adjusting for multiple comparisons.
CONCLUSIONS: Virologic failures in HT 001 were not explained by genetic polymorphisms known to define the lowest plasma efavirenz concentration stratum.
METHODS: We genotyped 76 polymorphisms in CYP2B6 (including those that define efavirenz concentration strata), CYP2A6, CYP3A4, CYP3A5 and ABCB1 and week 48 virologic responses in 360 Haitians who initiated efavirenz-containing regimens in protocol HT 001. Associations were characterized by logistic regression analysis and Fisher's exact test.
RESULTS: Proportions with HIV-1 RNA <50 or <200 copies/mL did not differ across 10 CYP2B6 metabolizer strata. In analyses that combined strata into three metabolizer levels (extensive, intermediate and slow), the respective proportions were 0.79, 0.79 and 0.81 (<50 copies/mL cut-off) and 0.84, 0.86 and 0.87 (<200 copies/mL cut-off). Genetic associations were not identified after controlling for baseline variables or with other polymorphisms after adjusting for multiple comparisons.
CONCLUSIONS: Virologic failures in HT 001 were not explained by genetic polymorphisms known to define the lowest plasma efavirenz concentration stratum.
Предметные рубрики MeSH
ATP Binding Cassette Transporter, Subfamily BAdultAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6Cytochrome P-450 CYP2B6 InducersCytochrome P-450 CYP3AFemaleGenetic Association StudiesHIV InfectionsHIV-1HaitiHumansMaleMiddle AgedPolymorphism, Single NucleotideProspective StudiesRNA, ViralReverse Transcriptase InhibitorsSecondary MetabolismTreatment Outcome