Two male patients with HIV, aged 61 and 58 years, presented with slowly progressive renal failure. Both had been treated with highly active antiretroviral therapy (HAART) for several years. Additional laboratory investigations showed hypophosphatemia, hypouricemia, metabolic acidosis and normoglycemic glucosuria. These results are an indication of proximal tubular dysfunction (PTD). Complete PTD is also known as Fanconi syndrome. Other laboratory abnormalities in Fanconi syndrome include aminoaciduria, phosphaturia and β2-microglobulinuria. Fanconi syndrome is a side effect of tenofovir. Recent work demonstrates that up to 22% of tenofovir users display subtle abnormalities of the proximal tubule. Intracellular accumulation of tenofovir is toxic for the proximal tubular cell. This may be related to the concomitant use of ritonavir which inhibits the active transport of tenofovir from the proximal tubular cell to pre-urine. Possible consequences of prolonged PTD are osteomalacia and progressive renal failure. Medication-induced PTD should be considered in patients using antiretrovirals who develop electrolyte disorders, urinary sediment abnormalities or glucosuria.