Toxicity Potentials of Dolutegravir-Base Antiretroviral Therapy on the Ovary and Uterus of Adult Wistar Rats

Background: Human immunodeficiency virus (HIV) remains a critical global health issue, with 88.4 million infections and 42.3 million AIDS-related deaths to date. In 2024 alone, 39.9 million individuals are living with HIV, 630,000 deaths occurred, and 1.3 million new infections were recorded. Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir (TLD) is a widely used antiretroviral therapy, but its reproductive and oxidative effects remain underexplored in female models, particularly in the South-South region of Nigeria.Objective: This study aimed to evaluate the reproductive toxicity and oxidative stress effects of TLD on the ovaries and uterus of adult female Wistar rats.Methods: Ten adult female Wistar rats (156–187g) were divided into control and treatment groups (n=5). The control group received standard diet and distilled water, while the treated group received daily doses of TLD (Tenofovir 5 mg, Lamivudine 5 mg, and Dolutegravir 0.8 mg/kg body weight) for 90 days. At the end of the treatment, animals in estrus phase were sacrificed for biochemical, histological, and hormonal analysis.Results: The treated group showed a significant reduction in body weight but no significant changes in ovarian or uterine weight. Oxidative stress analysis revealed decreased MDA and increased SOD, GPx, and CAT in the uterus. Hormonal levels were not significantly different. Histologically, the treated group displayed impaired follicular development, atretic follicles, cysts, enlarged endometrial cavities, and thicker endometria.Conclusion: TLD administration induced notable reproductive alterations in female Wistar rats, highlighting potential implications for its use in women of reproductive age.