Chronic kidney disease (CKD) is currently considered a major comorbidity in patients affected by HIV infection. In addition, new generation antiretroviral drugs that interact with creatinine transporters were recently introduced. Rilpivirine, dolutegravir, and cobicistat, with different mechanisms, inhibit the amount of tubular secretion of creatinine causing a slight increase in serum creatinine levels and consensual eGFRcreat reduction. This will require an unprecedented attention to renal issues, because the new drugs can also be associated to old antiretroviral drugs that may exert renal toxic effects. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimating GFR would be desirable. At the moment, methods of direct GFR measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate GFR is still recommended, considering the apparent reduction of eGFRcreat due to these drugs. Tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid. More specific and sensitive markers of tubular damage are still not readily available in all clinical labs. HIV patients treated by the novel drugs need to be monitored on a monthly basis for the first 3 months. Subsequent monitoring should be performed on a quarterly basis or guided by comorbidities.