Background: The number of human immunodeficiency virus (HIV)-infected patients has increased significantly, although the number of deaths due to HIV and acquired immunodeficiency syndrome (AIDS) has dramatically reduced. Highly active antiretroviral therapy (HAART) has increased not only survival but also the risk of deaths caused by other diseases or by long-term side effects of these drugs. AIM: The aim of this study is to evaluate the nephrotoxicity of one of the most common anti-retroviral drugs, tenofovir disoproxil fumarate (TDF). Materials and Methods: We examined 27 patients with HIV infection (10 women). Patients assumed TDF for a mean period of 8.03 months. Indexes of renal function and serum electrolytes were measured, and glomerular filtration rate was estimated (eGFR). Proteinuria, glycosuria, bicarbonaturia, and phosphaturia were assessed, and renal ultrasound examination was carried out. Results: Acute kidney injury with glycosuria, bicarbonaturia, and phosphaturia was seen in 22 patients. Substantial recovery of renal function occurred in 19 patients. Conclusion: This study highlights that TDF nephrotoxicity is a widely frequent but reversible form of renal damage with preferentially proximal tubular dysfunction. We suggest that all patients at the time of HIV diagnosis should carry out a screening for kidney disease with eGFR assessment, proteinuria, and urine analysis.