ABSTRACT
ABSTRACT Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/adverse effects , Time Factors , Brazil , Zidovudine/adverse effects , Logistic Models , Risk Factors , Acquired Immunodeficiency Syndrome/mortality , Ritonavir/adverse effects , Lamivudine/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Benzoxazines/adverse effects , Drug Combinations , Kaplan-Meier Estimate , Lopinavir/adverse effects , Tenofovir/adverse effectsABSTRACT
ABSTRACT This study aimed to identify the 516 G>T polymorphism of the CYP2B6 gene and evaluate its influence on central nervous system (CNS) side effect development in HIV-positive individuals undergoing Efavirenz (EFV) treatment in a population from southern Brazil. Additionally, we performed a survey on the clinical and epidemiological characteristics of our sample. In addition to medical records evaluation, whole blood of 89 individuals was analyzed for viral load, T lymphocyte count (CD4+ and CD8+), and the polymorphism. Considering the side effects of the CNS reported by individuals but without considering the genetic variables, no statistically significant association was noted between the adverse effects and the antiretroviral treatment (including or not EFV). In addition, no statistically significant difference was noted for the influence of genotype on the viral load or the number of T lymphocytes (CD4+ and CD8+) among individuals undergoing EFV treatment. This is the first study that investigated the impact of the 516 G>T polymorphism of the CYP2B6 gene among HIV-positive individuals from southern Brazil. Its clinical significance indicates the need for prospective studies in this population.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Polymorphism, Genetic/genetics , HIV Infections/genetics , HIV Infections/drug therapy , Central Nervous System/drug effects , Reverse Transcriptase Inhibitors/adverse effects , Benzoxazines/adverse effects , Cytochrome P-450 CYP2B6/genetics , Prospective Studies , CD4-CD8 Ratio , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load , Benzoxazines/therapeutic use , GenotypeABSTRACT
The effects of chronic administration of efavirenz commonly used as part of highly active antiretroviral therapy (HAART) for the treatment of Human Immunodeficiency Virus (HIV) type-1 therapy on the chromatophilic substance of the intracranial auditory relay centre namely the inferior colliculus and medial geniculate body of adult wistar rats were carefully studied. The rats of both sexes (n=20), with an average weight of 200g were randomly assigned into treatment (n=10) and control (n=10) groups. The rats in the treatment group received 600 mg/70kg body weight of efavirenz dissolved in distilled water daily for 30 days through the orogastric tube. The control group received equal volume of distilled water daily for 30 days through the same route. The rats were fed with grower's mash obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and given water liberally. The rats were sacrificed by cervical dislocation method on the thirty-first day of the experiment. The inferior colliculus and medial geniculate body were carefully dissected out and quickly fixed in 10 percent formal saline for histological study. The histological findings indicated that the treated sections of the inferior colliculus and medial geniculate body showed that the chromatophilics substances were less intensely stained as compared to the control. The parenchyme was vacuolated and with evidence of hypertrophy and more spaces between the axonal mesh around the sparsely distributed neurons as compared to the control group. The treated section of the inferior colliculus showed neurons with faintly stained chromatophilics substances in large, medium and small sized neurons while that of the medial geniculate body showed less intense and enlarge chromatophilics substances with some vacuolations. Chronic administration of efavirenz may therefore have an adverse effect on the chromatophilics substances of the inferior colliculus and medial geniculate body of adult wistar rats...
Fueron estudiados los efectos de la administración crónica del efavirenz, comúnmente utilizado como parte del tratamiento antirretroviral de gran actividad para el VIH tipo 1, sobre la sustancia cromatofílica del centro de relevo auditivo intracraneal, el colículo inferior y cuerpo geniculado medial, en ratas Wistar adultas. Ratas de ambos sexos (n = 20), con un peso promedio de 200g fueron asignadas aleatoriamente a tratamiento (n = 10) y control (n = 10). Las ratas del grupo tratado recibieron 600mg/70kg peso corporal de efavirenz disuelto en agua destilada durante 30 días a través de sonda orogástrica. El grupo de control recibió un volumen igual de agua destilada durante 30 días por la misma vía. Las ratas fueron alimentadas con puré agricultor obtenido de Edo Feeds and Flour Mill Limited, Ewu, estado de Edo, Nigeria y agua ad-libitum. Las ratas se sacrificaron por dislocación cervical el día 31. El colículo inferior y el cuerpo geniculado medial fueron disecados cuidadosamente y se fijaron en solución de formalina salina al 10 por ciento. Los hallazgos histológicos indicaron que en las secciones tratadas del colículo inferior y el cuerpo geniculado medial la sustancia cromatofílica fue menos intensamente teñidas en comparación con el control. El parénquima se vacuoló, con evidencia de hipertrofia y más espacios entre la red axonal alrededor de neuronas escasamente distribuidas en comparación con el grupo control. La sección tratada del colículo inferior mostró neuronas con sustancia cromatofílica débilmente teñida en las neuronas de tamaño grande, mediano y pequeño, mientras que las del cuerpo geniculado medial mostraron sustancia cromatofílica menos intensa, con algunas vacuolaciones amplias. La administración crónica de efavirenz puede tener un efecto adverso sobre las sustancias cromatofílica del colículo inferior y del cuerpo geniculado medial de ratas Wistar adultas. Se recomienda realizar estudios adicionales...