Investigation of the neurological effects of dolutegravir in male Sprague-Dawley rats

Abstract

Dolutegravir (DTG), a primary integrase strand transfer inhibitor used in antiretroviral therapy, has been associated with neuropsychiatric side effects. This study examined the neurotoxicity of DTG in a rat model by evaluating behavioral alterations using the T-maze test for spatial memory and the beam-balance test for motor coordination. Fifty male Sprague-Dawley rats (mean body weight: 216.8 g) were randomly allocated into five groups (n = 10 per group). Treatments were administered by oral gavage (1 mL per rat) once daily for six weeks. The treatments were as follows: Group 1 received 0.9% saline (negative control); Group 2 received 100 mg/kg aluminium trichloride (positive control); and Groups 3–5 received DTG at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg, respectively. Behavioral testing was performed biweekly, and plasma neurofilament light chain (NfL) concentrations were quantified by ELISA at week 6. T-maze performance showed dose- and time-dependent cognitive impairment. By week 6, correct alternations were 71.3 ± 4.2% at 5 mg/kg, 58.7 ± 4.8% at 10 mg/kg, and 39.5% at 20 mg/kg. Beam-balance performance remained intact at the lowest dose, whereas the higher doses produced mild deficits. NfL concentrations were elevated in all DTG groups, with greater elevations observed at higher doses, indicating dose-related neuroaxonal injury that was detectable even when behavioural deficits were minimal. These findings indicate that DTG may cause subclinical neurotoxicity.