Burden of Neuropsychiatric Adverse Effects and Changes in Weight Among Hiv Infected Patients Switched From an Efavirenz Based to a Dolutegravir Based First Line Regimen at the Kenyatta National Hospital.

Abstract

Background: Current WHO guidelines recommend the use of integrase strand transfer inhibitors (INSTIs) as the first line alternative to efavirenz (EFV). Compared to EFV, INSTIs are associated with fewer adverse effects, less drug interactions and a higher genetic barrier to resistance (2). Several concerns are emerging regarding the adverse effects INSTIs especially their effects on weight and the neuropsychiatric adverse effects (NP-AEs). There is limited data in Kenya on the adverse effects of INSTIs among patients initiated on or switched to dolutegravir (DTG) as a first line alternative to EFV. Objectives: The main objective of this study was to compare the changes in body weight over a 6 month period and burden of neuropsychiatric adverse effects (NP-AEs) among HIV infected patients switched to a DTG-based regimen versus those on an EFV-based regimen. Some of the factors associated with excess weight gain and NP-AEs were also explored. Methodology: This was a retrospective cohort study with a cross sectional arm, carried out at the KNH Comprehensive Care Clinic over a period of 3 months. Participants who met the inclusion criteria and gave written informed consent were enrolled into the study. A study proforma was used to obtain socio-demographic and clinical data including the changes in body weight over a period of 6 months. CNS toxicity and insomnia severity index questionnaire were used to establish the presence and severity of the NP-AEs. Data analysis was done using SPSS version 21.0 (Chicago- Illinois). A p value of ≤ 0.05 was interpreted as significant. Results: 526 participants were included in the study; 272 had been switched to a DTG-based regimen and 254 were on an EFV-based regimen. Participants on DTG gained significantly more weight at 6 months (mean +2.4kg, SD 3.9, 95% CI 1.9-2.9) compared to those on EFV (mean +0.2kg, SD 2.7, 95% CI 0.14-0.5). 18% of the participants on DTG had excess weight gain (≥ 10% increase in body weight or progression to a higher BMI category for those with initially normal BMI) compared to 7.1% among those on EFV (95% CI [1.6- 5.1], p<0.001). Being on a DTG-based regimen was the main factor associated with excess weight gain even after adjusting for variables such as age and gender. The burden of NP-AEs was higher among participants on EFV compared to those on DTG (29.5% versus 22.8% respectively, [p=0.079]). There was no significant difference in the burden of insomnia among participants in the two study groups (p=0.381). On multivariate analysis, mean antiretroviral therapy (ART) duration was significantly associated with NP-AEs (OR 1.15, [95% CI 1.07-1.23], p<0.01). Conclusion: Our study showed that patients on DTG-based ART regimen gain significantly more weight compared to those on EFV-based regimens. The prevalence of neuropsychiatric adverse effects and neuropsychiatric toxicity was higher among patients on EFV-based regimen