November 21, 2002
HIV disease may be associated with renal impairment. This may be secondary to HIV itself, i.e., associated with HIV immunosuppression or due to the drugs used to treat HIV disease. Tenofovir (TDF, Viread) is a newly licensed nucleotide analogue that is eliminated unchanged by the kidney via glomerular infiltration and active tubular secretion. It would be therefore expected that dose modification of tenofovir would be necessary for individuals with significant renal dysfunction.
Individuals who were either healthy or renally impaired and non-HIV infected were recruited to this study. Participants were found to have either normal, mild, moderate or severe renal impairment based on their creatine clearance, which is a measure of renal function. In individuals with mild impairment, there appears to be no difference in the pharmacokinetics of tenofovir elimination. However, in patients with moderate and severe dysfunction there was an increase in the Cmax (that is maximum level of drug reached) and the area under the curve (i.e., total exposure to tenofovir). Of the 41 subjects who were exposed to the drug, 13 experienced adverse events, although only one of these was serious and not related to the study drug.
Tenofovir was well tolerated in individuals with renal dysfunction. For individuals experiencing moderate or severe impairment in kidney function, dose reduction of tenofovir is necessary due to the higher systemic exposure to the drug.
Adefovir, the sister drug of tenofovir, has recently been licensed for the treatment of hepatitis B. Adefovir was originally studied for the treatment of HIV, but much higher doses of the drug were needed to suppress HIV viral replication than is needed to treat hepatitis B and these doses were associated with renal dysfunction. Within studies investigating tenofovir there has been no excess of renal dysfunction compared with individuals receiving placebo. This study shows that tenofovir may be safely given to individuals with renal dysfunction and HIV, although dose modification is necessary. The poster did not state recommendations regarding exact dose modifications.
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