December 16, 2005
First-line treatment with tenofovir (TDF, Viread) has not been associated with higher rates of kidney failure when compared with more commonly prescribed antiretroviral agents. However, Fanconi syndrome, a condition in which impaired kidney function causes certain compounds to be excreted in the urine instead of reabsorbed back into the bloodstream, and renal failure have occasionally been observed in patients receiving tenofovir-based antiretroviral therapy. At the same time, the long-term consequences of tenofovir use in regard to kidney function are not well understood.
To address the concern among clinicians that tenofovir may cause kidney toxicity with extended treatment, the current study evaluated the changes in the levels of uric acid and phosphorus in patients undergoing long-term tenofovir therapy.
Investigators based at the major university teaching hospital in Elche, Spain, which has been a leading study site investigating long-term tenofovir use, conducted the study. All individuals at the study site who had received tenofovir as part of their first-line therapy were included in the retrospective analysis (n = 122), and this group of patients was compared with individuals who had initiated therapy with regimens that did not include tenofovir (n = 194).
The results show that patients who initiated highly active antiretroviral therapy (HAART) with a tenofovir-based regimen were older (41.5 vs. 39.1 years; P = .03) and received drugs over a longer period of time (4.9 vs. 2.16 yrs; P < .01) than those who commenced therapy with other regimens.
Of the 122 individuals who began therapy with tenofovir, two discontinued tenofovir treatment during the 48 weeks of the study due to renal toxicity. Patients in the tenofovir group seemed to display somewhat lower serum phosphorus levels over the 48 weeks of evaluation (3.22, 2.99 and 2.02 mg/dL at baseline, 24 weeks and 48 weeks, respectively; P = .078), while serum uric acid levels decreased significantly from 5.30 at baseline to 4.42 and 4.43 mg/dL at 24 and 48 weeks of therapy, respectively (P < .001).
In accord with these changes, a higher proportion of individuals in the tenofovir group were reported to have developed at least grade 1 or grade 2 hypophosphatemia, or low phosphate levels, than in the non-tenofovir group, thereby suggesting that tenofovir may be associated with these changes.
Although this study does seem to demonstrate that tenofovir may be associated with modest decreases in uric acid and phosphorus levels in the serum of treatment-naive patients, it should be emphasized that these data appear to be inconsistent with those reported in abstract H-350 for the Gilead 903 study, which appears to be far better controlled than the current study. For example, the study assessing the Gilead 903 data directly compared two drugs -- that is, tenofovir versus stavudine (d4T, Zerit) -- and found no evidence of drug-related nephrotoxicity in either treatment arm over 144 weeks. In contrast, the present study included a wide array of antiviral agents that were not studied in any organized fashion. Although the current study does establish some concern that long-term tenofovir treatment may impair kidney function, these findings should not be over-interpreted at this time in light of the data presented for the Gilead 903 study.