Abstract:
Purpose 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 cotreatment
on efavirenz-associated neuropsychiatric manifestations.
Methods 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 HIVTB
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.
Results 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 cARTcompared 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).
Conclusions 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.
