Histological and Oxidative Stress Toxicity of Dolutegravir-Based Antiretroviral Therapy on the Placenta of Adult Wistar Rats

Tenofovir Disoproxil Fumurate/Lamivudine/Dolutegravir (TLD) is a fixed dose combination antiretroviral therapy recommended by World Health Organization (WHO) as preferred first and second-line antiretroviral therapy for people living with HIV. However, a relationship between placenta histology and oxidative toxicity of TLD is unknown. This study was designed to investigate the histological and oxidative stress toxicity of TLD on the placenta of adult Wistar rats. Ten rats weighing between 154-194g were randomly assigned into two groups; a control and TLD-treated. After pregnancy was achieved, the treated group was still administered combination drugs of Tenofovir Disoproxil Fumurate in 5mg/kg, Lamivudine in 5mg/kg and Dolutegravir in 0.8mg/kg body weight daily for 90 days. Dams were weighed on gestational day (GD) 0, 7, 14 and 21. At GD21, the dams were sacrificed, and placenta were harvested, counted, weighed, measured, and submitted for biochemical oxidative stress assessments and a section taken for histological evaluation. The findings revealed significant decrease in the body weight, placenta weight, diameter, and thickness of the treated group. Also, there was a significant decreased in placenta tissue reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase was decreased with insignificant difference, the concentration of malondialdehyde increased with insignificant difference in the treated compared to the control group. There was no significant difference in the number of number of placenta between the control and treated groups. The placenta histology of the TLD treated revealed vacuolation, congestion, and dilatation of the fetal-maternal vascular bed. These findings suggest TLD administration during pregnancy have negative effects on the placenta and could lead to abortion or cause serious negative consequences for the developing foetus. Concerns over long-term usage; especially during pregnancy, cannot be overemphasized.