Introduction: Exposure to Tenofovir often leads to the development of some irreversible high risk for kidney disease events. In Human Immunodeficiency Virus (HIV) patients, the prolonged treatment with tenofovir use frequently causes mildto-moderate nephrotoxicity. Hence, there is a need to further investigate the efficacy and the adverse effects associated with tenofovir use to combat the decreased morbidity and mortality associated with the declined kidney function. Aim: To investigate the risk of kidney disease associated with tenofovir use. Materials and Methods: A retrospective study was conducted at the tertiary care centre in northern India, from August 2009 to January 2017 and analysed during January to May 2021. The patients with HIV infection who were administered Tenofovir, Lamivudine and Efavirenz (TLE) and Zidovudine, Lamivudine and Nevirapine (ZLN) were included.The patients were divided into two group based on the TLE and ZLN regimen they received. These patients were on a regular follow-up for six months. The data was assessed on the basis of serum creatinine and estimated Glomerular Filtration Rate (eGFR) (using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation), body weight and Cluster of Differentiation (CD4) count. Results: Out of 703 patients, 364 patients were administered with TLE, while 339 patients received ZLN. In both the groups, the number of patients were between the age 21-40 years was significantly higher, followed by patients between the age 41- 60 years. The mean weight and CD4 count of the patients in both the groups significantly increased with the progression of time (p<0.001). The creatinine levels at baseline and at 24 months were comparable in both the groups, p>0.05. The mean eGFR level was significantly lowered in TLE group (112.2 mL/ min/1.73 m2 ) compared to ZLN group (123.5 mL/min/1.73m2 ) at 24-months follow-up (p<0.001). Conclusion: Overall results demonstrate that increasing exposure to tenofovir was associated with a higher incidence of CKD. The serum creatinine levels were comparable between the TLE and ZLN group.