Abstract
Few studies have reported analyses of neuropsychiatric impairment (NPI) data from HIV patients, in a real world clinical setting with the aim of establishing association between anti-retroviral drug concentrations and NPI development and resolution. No study has modeled the effect of efavirenz exposure beyond the pre-steady state period on the frequency and duration of NPI. The data used consists of 196 HIV patients whose efavirenz pharmacokinetic parameters were previously determined. Neuropsychiatric evaluation was done at baseline, week 2 and week 12. Patients were classified into NORMAL and NPI states. The duration of NPI was further classified as transient (NPI at week 2 but not at week 12), persistent (NPI at week 2 and 12) and delayed (NPI at week 12 but not at week 2). The proportion of patients in each duration category out of the total NPI patients was calculated. A continuous time Markov model was developed in NONMEM 7.3 and used to describe the relationship between efavirenz exposure and the duration of NPI. Monte Carlo simulations with the model were used to describe the effect of efavirenz dose reduction from 600mg to 400mg on the duration of NPI. The model adequately described the data. The influence of efavirenz exposure on the rate of development of NPI decayed with a half-life of 8.4 days. Efavirenz dose reduction to 400mg significantly reduces the duration of NPI, but has no impact on delayed NPI symptoms or efficacy.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
