rifampin and Mental-Disorders

Efavirenz-based combination antiretroviral therapy (cART) is associated with neuropsychiatric adverse events. We investigated the time to onset, duration, clinical implications, impact of pharmacogenetic variations, and anti-tuberculosis co-treatment on efavirenz-associated neuropsychiatric manifestations.. Prospective cohort study of cART naïve HIV patients with or without tuberculosis (HIV-TB) co-infection treated with efavirenz-based cART. Rifampicin-based anti-tuberculosis therapy was initiated 4 weeks prior to efavirenz-based cART in HIV-TB patients. Data on demographic, clinical, laboratory, and a 29-item questionnaire on neuropsychiatric manifestations were collected for 16 weeks after cART initiation. Genotyping for CYP2B6, CYP3A5, SLCO1B1, and ABCB1 and quantification of efavirenz plasma concentration were done on the 4th and 16th week.. Data from 458 patients (243 HIV-only and 215 HIV-TB) were analyzed. Overall incidence of neuropsychiatric manifestations was 57.6% being higher in HIV-only (66.7%) compared to HIV-TB patients (47.4%) (p < 0.01). HIV-only patients were more symptomatic, with proportionately higher grades of manifestations compared to HIV-TB patients. Median time to manifestations was 1 week after cART initiation in HIV-only and 6 weeks after anti-TB (i.e., 2 weeks after cART initiation) in HIV-TB patients. HIV-only patients had significantly higher efavirenz plasma concentrations at 4 weeks after cART compared to HIV-TB patients. No association of sex or genotype was seen in relation to neuropsychiatric manifestations. Risk for neuropsychiatric manifestations was three times more in HIV-only patients compared to HIV-TB (p < 0.01).. Incidence of neuropsychiatric manifestations during early initiation of efavirenz-based cART is high in Tanzanian HIV patients. Risk of neuropsychiatric manifestations is lower in HIV patients co-treated with rifampicin containing anti-TB compared to those treated with efavirenz-based cART only.

Topics: Adult; Africa South of the Sahara; Alkynes; Anti-HIV Agents; Antibiotics, Antitubercular; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; Cohort Studies; Cyclopropanes; Female; Genotype; HIV Infections; HIV-1; Humans; Male; Mental Disorders; Pharmacogenetics; Prospective Studies; Rifampin; Tuberculosis

HIV infection, anti-tuberculosis and efavirenz therapy are associated with neuropsychological effects. We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection.. 197 treatment naïve Ugandan HIV patients, of whom 138 were TB co-infected, enrolled prospectively and received efavirenz based HAART. TB-HIV confected patients received concomitant rifampicin based anti-TB therapy. Genotypes for CYP2B6 (*6, *11), CYP3A5 (*3, *6, *7), ABCB1 (c.3435C>T and c.4036 A/G rs3842), CYP2A6 (*9, *17) and NR1I3 rs3003596 T/C were determined. Efavirenz plasma concentrations were serially quantified at 3rd day, 1st, 2nd, 4th, 6th, 8th and 12th weeks during therapy. Efavirenz neuropsychiatric symptoms were evaluated in terms of sleep disorders, hallucinations and cognitive effects at baseline, at two and twelve weeks of efavirenz treatment using a modified Mini Mental State Examination (MMSE) score.. During the first twelve weeks of ART, 73.6% of the patients experienced at least one efavirenz related neuropsychiatric symptom. Commonest symptoms experienced were sleep disorders 60.5% (n=124) and hallucination 30.7% (n=63). Neuropsychiatric symptoms during HAART were significantly predicted by efavirenz plasma concentrations consistently. Rifampicin cotreatment reduced plasma efavirenz concentrations significantly only during the first week but not afterwards. There was no significant difference in the incidence of neuropsychiatric symptoms between patients receiving efavirenz with or without rifampicin cotreatment. CYP2B6*6 and ABCB1 c.4036 A/G genotype significantly predicted efavirenz concentrations. The tendency of CYP2B6*6 genotype association with higher incidence of having vivid dream (p=0.05), insomnia (p=0.19) and tactile hallucination (p=0.09) was observed mainly at week-2.. Efavirenz related neuropsychiatric symptoms are common among Ugandan HIV patients receiving ART and is mainly predicted by higher efavirenz plasma concentrations and CYP2B6 genotype but not by rifampicin based anti-TB co-treatment.

Topics: Adult; Alkynes; Anti-HIV Agents; Antibiotics, Antitubercular; Antiretroviral Therapy, Highly Active; Aryl Hydrocarbon Hydroxylases; Benzoxazines; Cognitive Dysfunction; Constitutive Androstane Receptor; Cyclopropanes; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP3A; Female; Gene Frequency; Hallucinations; HIV Infections; Humans; Kaplan-Meier Estimate; Male; Memory Disorders; Mental Disorders; Prospective Studies; Rifampin; Sleep Arousal Disorders; Tuberculosis; Uganda

Topics: Antigens, Bacterial; Biomarkers; Ciprofloxacin; Diagnosis, Differential; Drug Therapy, Combination; Erythromycin; Humans; Legionella pneumophila; Legionnaires' Disease; Male; Mental Disorders; Middle Aged; Rifampin; Serologic Tests; Tomography, X-Ray Computed; Treatment Outcome

A 5 year old girl with tuberculous meningitis developed progressive visual failure during in-patient anti-tuberculous chemotherapy due to an ophthochiasmatic tuberculoma. This was successfully managed by prolonged high-dose corticosteroids and continued anti-tuberculous therapy resulting in complete visual and psychosocial recovery.

Topics: Child, Preschool; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoniazid; Mental Disorders; Optic Chiasm; Optic Nerve Diseases; Pyrazinamide; Pyridoxine; Rifampin; Streptomycin; Tuberculoma, Intracranial; Vision Disorders

Topics: Aminosalicylic Acids; Animals; Antitubercular Agents; Capreomycin; Chemical and Drug Induced Liver Injury; Cycloserine; Deafness; Drug Hypersensitivity; Ethambutol; Ethionamide; Gastrointestinal Diseases; Goiter; Humans; Isoniazid; Kanamycin; Liver; Mental Disorders; Mice; Nervous System Diseases; Pyrazinamide; Rifampin; Streptomycin; Thioacetazone; Tuberculosis; Viomycin

Topics: Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Chronic Disease; Drug Therapy, Combination; Eosinophilia; Ethambutol; Female; Gastrointestinal Diseases; Humans; Kidney; Liver; Male; Mental Disorders; Middle Aged; Radiography; Rifampin; Sputum; Tuberculosis, Pulmonary; Vertigo; Vision Disorders

Topics: Chronic Disease; Coma; Dactinomycin; Daunorubicin; Dexamethasone; Encephalomyelitis; Fever; Headache; Humans; Idoxuridine; Leukopenia; Meningitis, Viral; Mental Disorders; Pain; Paralysis; Respiratory Insufficiency; Rifampin; Vomiting