Tenofovir use in a patient with a severe renal impairment

Abstract

Tenofovir fumarate (TDF) is the first nucleoside reverse transcriptase inhibitor (NRTI) licensed for treatment of HIV infections in patients who have failed previous antiretroviral treatment as well as in treatment-naive patients [1]. Some authors have reported a possible role of TDF in inducing renal failure or tubular dysfunction [2–5]. Furthermore, it has been reported that triple NRTI therapy containing TDF is associated with unacceptable failure rates [6,7]. Recently, TDF pharmacokinetics following single-dose administration was evaluated in a clinical study involving 41 volunteers with renal impairment [8]. We report a case of a patient with a severe renal impairment treated with TDF. The patient was a 33-year-old Caucasian woman who had been followed by our institution since 1989 for HIV infection, acquired through sexual intercourse. Her past history included juvenile diabetes since 1990; subsequently, she had diabetes-correlated polyneuropathy (1992), retinopathy (1998) and severe renal impairment (2001), which required weekly haemodialysis. She has been treated with several antiretroviral combinations, including protease inhibitors (PIs). Previous regimens were stopped because of the insurgence of severe side effects, such as hyperamylasaemia (didanosine), leucopaenia and anaemia (zidovudine), and hyperglycaemia and renal impairment (ritonavir, nelfinavir and lopinavir/ritonavir), and also because of genotypic resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). In March 2003, blood examination revealed a CD4 cell count of 117 cells/μL (11%), a viral load of 19 900 HIV-1 RNA copies/mL, a white blood cell count of 6.2 × 103 cells/μL, a serum creatinine concentration of 11 mg/dL and an amylase concentration of 201 U/L. On the basis of HIV viral genotype, uncontrolled diabetes and poor adherence to complicated highly active antiretroviral therapy (HAART), the patient was started on abacavir [300 mg twice a day (bid)], lamivudine (37.5 mg once a day (qd)] and TDF (300 mg once weekly). Doses of lamivudine and TDF were adjusted on the basis of her renal insufficiency following the prescribing information [9,10]. Dosing interval adjustment is recommended for all patients with a creatine clearance of <50 mL/min, as follows: 300 mg once every 2 days for a creatine clearance of 30–49 mL/min and twice weekly for a creatine clearance of 10–29 mL/min. For patients on haemodialysis, a dose of 300 mg once a week after completion of a total of 12 h of high-flux haemodialysis (determined on the basis of data from 4 h of dialysis 3 times per week) is recommended [10]. After 4 weeks of treatment, the CD4 cell count was 191 cells/μL (12%), the viral load was 1060 copies/mL and the creatinine concentration was 8.4 mg/dL. Four months later, the CD4 cell count was 218 cells/μL (12%), the viral load was undetectable and the creatinine concentration was 8.9 mg/dL. After 32 weeks, the CD4 cell count was 228 cells/μL (14%), the viral load was undetectable and the creatinine concentration was 9 mg/dL. The patient is on a waiting list for a kidney transplant. In this case, we found that TDF once weekly associated with abacavir and lamivudine was well tolerated. In particular, no worsening of renal impairment was observed, with constant blood creatinine values after 16 and 32 weeks. During tenofovir therapy, no signs of toxicity (hepatic or haematological) or other adverse events were observed. According to standard practice, this patient would have required a more active antiretroviral treatment than a triple NRTI regimen (which is not recommended, particularly when the initial viral load is above 100 000 copies/mL) [6,7], we decided to initiate this regimen on the basis of available pharmacokinetic data [8]. In this particular case, we found this regimen to have durable efficacy and favourable tolerability. Further pharmacokinetic evaluation will allow better tailoring of the dosage of TDF in patients with severe renal insufficiency.