Background: Human Immuno-deficiency Virus (HIV) remains a major global public health issue. However, it is now considered a chronic infection which can be managed with new, well-tolerated and efficacious ARVs. The aim of the study was to evaluate the effect of Tenofovir/Lamivudine/Dolutrgravir (TLD) on the HRQoL and viral suppression over a short period.Method: The study was prospective, with a time frame of three (3) months. HRQoL was measured using a disease specific HIV/AID Targeted Quality of Life (HAT-QoL) tool and the clinical outcomes focused on viral load using structured data collection tool.Results: Most of the participants were female (62.1%), currently married 63.2% and no co-morbidity, mean age 43±SD (range 21-77years). There was a statistically significant improvement in HRQoL scores across all domain after 3months of transitioning to TLD. While 8 of the 9 domains namely; overall functions, life satisfaction, health worries, financial worries, medication worries, HIV mastery, Disclosure worries, Provider trust, (p <0.001) sexual function (p =0.015). Improvement was also seen in viral suppression (p <0.001).Using multiple linear regression analysis, predictors for overall HRQol scores include female gender (ᵝ= 3.59, 95%CI 1.30-5.78, p=0.002), older age, >65years (ᵝ= 4.12, 95%CI -1.42,9.67 p=0.08), living with family (ᵝ= -5.80, 95%CI -9.60,-2.00, p=0.003), higher family income, >N100,000 (ᵝ= 6.09, 95%CI 1.75,10.44, p=0.006) and duration on ART (ᵝ=0.52, 95%CI 0.12, 0.91, p=0.01). While determinants of viral suppression using multi-variant logistic regression analysis revealed living with family (AOR=18.03, 95%CI 3.32-97.85, p<0.001), Primary education (AOR= 0.16, 965%CI 0.029,0.93, P=0.041), being employed (AOR=0.16, 95%CI 0.028,0.91, P=0.008), income and baseline viral load (AOR= 0.53, 95%CI 0.44,0.69, p<0.001). However, living with family is major determinant of viral suppression.Conclusion: TLD help improved health related quality of life among HIV infected individual and essential in rapid viral suppression.