Tenofovir is no more likely than d4T to cause kidney toxicities in treatment-naive patients when combined with 3TC and efavirenz, according to the results of an international study presented as a poster to the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago on September 15th.
There have been several case reports of tenofovir-associated kidney toxicities since the drug was licensed. The results of this study, a double blind international trial which involved 592 treatment-naive patients, who were divided equally between a tenofovir and d4T arm, will help clarify just how frequent tenfovir-related kidney toxicities are in treatment-naive patients.
At baseline, patients were required to have an HIV viral load of at least 5,000 copies/mL. There was no minimum CD4 cell count requirement. At pre-trial screening patients had checks on their kidney function performed and were required to have serum creatinine =2.2mg/dL and calculated creatinine clearance >=60ml/min. On entry to the study, patients were randomised to receive either tenofovir or d4T with 3TC and efavirenz. As the daily dose of tenofovir is one pill daily, and at the time of the study d4T was always dosed with one pill twice daily, patients in the tenofovir arm took a placebo for one of their doses to ensure that they were taking the same number of pills as patients in the d4T arm.
Through the 96 weeks of the study, no cases of the severe kidney disorder Fanconi’s Syndrome were recorded. Levels of serum creatinine and serum phosphorus were comparable between patients in the two arms, with similar proportions of patients developing proteinuria (tenofovir 18% versus d4T 21%) and glucosuria (tenofovir and d4T 2%). Mean change from baseline in calculated creatinine clearance was also comparable between tenofovir and d4T (tenofovir baseline 122mL/min, 96 week data 123mL/min versus d4T baseline 125mL/min, 96 week data 129mL/min).
The investigators concluded that the renal safety profiles of tenofovir and d4T were similar when combined with 3TC and efavirenz.
Gallant J et al. Similar 96-week renal safety profile of tenofovir DF versus stavudine (d4T) when used in combination with lamivudine (3TC) and efavirenz in antiretroviral naive patients. 43rd ICAAC, abstract H-840, Chicago 14 - 17th September, 2003.