RESUMEN
Background: We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States. Methods: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Associations were evaluated with weighted Cox proportional hazards models stratified by race/ethnicity. Additional analyses adjusted for genetic ancestry and selected covariates. Results: Among 1833 participants, suicidality was documented in 41 in exposed analyses, and 34 in on-treatment analyses. In unadjusted analyses based on 12 genotype levels, suicidality increased per level in exposed (hazard ratio, 1.11; 95% confidence interval, .96-1.27) and on-treatment 1.16; 1.01-1.34) analyses. In the on-treatment analysis, the association was strongest among white but nearly null among black participants. Considering 3 metabolizer levels (extensive, intermediate and slow), slow metabolizers were at increased risk. Results were similar after baseline covariate-adjustment for genetic ancestry, sex, age, weight, injection drug use history, and psychiatric history or recent psychoactive medication. Conclusions: Genotypes that predict higher plasma efavirenz exposure were associated with increased risk of suicidality. Strength of association varied by race/ethnicity.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Farmacogenética , Suicidio/etnología , Adulto , Alquinos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/sangre , Benzoxazinas/administración & dosificación , Benzoxazinas/sangre , Ciclopropanos , Citocromo P-450 CYP2A6/genética , Citocromo P-450 CYP2B6/genética , Etnicidad , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Grupos Raciales , Factores de Riesgo , Ideación Suicida , Resultado del TratamientoRESUMEN
Adult male rats were administered intrapleural (ipl) or intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), 24 h after being submitted to forced swim test (FST). Four hours after LPS challenge, an increase in pleural and peritoneal leukocyte and neutrophil counts in animals not exposed to FST was noted. FST induced a marked increase in pleural, but not in peritoneal, neutrophil leukocytosis. The results suggest that lowered mood may increase inflammatory response to LPS.