Tenofovir discontinuation could predispose to urolithiasis in atazanavir-treated patients.
Urolithiasis has been recognized as a potential complication of antiretroviral therapy. Protease inhibitors are the drugs most commonly involved: indinavir can cause renal colic in about 8% of patients and lopinavir/ritonavir has been associated with seven cases of nephrolithiasis. The occurrence of renal colic during treatment with atazanavir is a rare, but reported event. Here we describe the case of a 43 years-old male patient enrolled in a pilot study evaluating the efficacy, safety and tolerability of treatment simplification to a dual therapy with atazanavir/ritonavir plus lamivudine in HIV-positive patients with optimal virological response (AtLaS study). The study was conducted in accordance with the Declaration of Helsinki and national and institutional standards and was approved by local ethic committee; signed informed consent was collected from all participants. At baseline, the patient, treated with atazanavir/ ritonavir þ tenofovir þ lamivudine for 4 years, with a CD4 count of 718 cells/mL and an HIV-RNA < 50 copies/mL, without hepatitis B or C co-infection, discontinued tenofovir according to the study design. Eight weeks thereafter he was hospitalized for severe right flank pain and fever. Serum blood exams revealed increased creatinine (1.6 mg/dL) with normal calcium, phosphate and uric acid levels. Urinanalysis showed a pH of 6.5, with no calcium, phosphate and uric acid abnormalities. The same day a spontaneous urinary stone emission occurred. A renal TC scan performed 3 days later revealed a right pyelic dilatation without any other stone. Two stones, weighting 5.9 and 13.6 mg respectively, were analyzed. They were dissolved in 250 mL of 20% H2SO4 and the supernatants were injected in an HPLC-UV apparatus for atazanavir measurement, as previously described. Drug concentrations in the two stones were 3.72 and 3.33 mg/mL. The estimated total amount of atazanavir was 0.93 and 1.08 mg respectively, which corresponded to a percent compositionof atazanavir ranging from7.9% to15.8% (Fig. 1). Four and 12 weeks after tenofovir discontinuation, atazanavir plasma levels increased from 3.84 to 3.89 and 6.27 mg/mL, respectively (all samples collected 9 h after drug intake).