RESUMEN
Objectives: There are limited data regarding efavirenz pharmacogenetics in admixed populations. The Brazilian population is highly admixed. In a Brazilian cohort, we sought to characterize associations between efavirenz adverse effects (all-cause and CNS) and polymorphisms in seven genes known or suspected to affect efavirenz metabolism and transport. Methods: We studied 225 HIV-positive individuals who had been prescribed efavirenz-containing regimens at a hospital in Rio de Janeiro, Brazil. Eighty-nine cases had efavirenz adverse effects, including 43 with CNS adverse effects, while 136 controls had no adverse effect of any antiretroviral after treatment for at least 6 months. A total of 67 candidate polymorphisms in ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3 genes were selected for association analysis. Admixture was assessed using 28 ancestry-informative polymorphisms previously validated for the Brazilian population. Associations were evaluated with logistic regression models adjusted for sex and genetic ancestry. Results: There was extensive African, European and Native American admixture in the cohort. Increased all-cause adverse effects were associated with the CYP2B6 genotype combination 15582CC-516TT-983TT (OR = 7.26, P = 0.003) and with the CYP2B6 slow metabolizer group 516TT or 516GT-983CT (OR = 3.10, P = 0.04). CNS adverse effects were nominally associated with CYP3A4 rs4646437 (OR = 4.63, P = 0.014), but not after adjusting for multiple comparisons. Conclusions: In a highly admixed Brazilian cohort, the CYP2B6 slow metabolizer genotype was associated with an increased risk of efavirenz adverse effects.
Asunto(s)
Benzoxazinas/efectos adversos , Benzoxazinas/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Infecciones por VIH/tratamiento farmacológico , Inactivación Metabólica/genética , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/metabolismo , Adulto , Anciano , Alquinos , Benzoxazinas/administración & dosificación , Brasil , Receptor de Androstano Constitutivo , Ciclopropanos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Inhibidores de la Transcriptasa Inversa/administración & dosificaciónRESUMEN
Neurofibromatosis type 1 (NF1) and AIDS are risk factors for the development of malignant neoplasms, including hematological malignancies, such as non-Hodgkin lymphoma. NF1 is an autosomal dominant disease that primarily manifests as café-au-lait spots, dermal neurofibromas, axillary and/or inguinal ephelides or freckles, plexiform neurofibromas, Lisch nodules, and bone deformities. In this report, we present a 38-year-old female patient with NF1 from childhood and AIDS who developed peripheral T-cell lymphoma with good response to chemotherapeutic treatment.