Over 144 Weeks Tenofovir and Stavudine Exhibit Similar Renal Safety Profiles in Treatment-naïve HIV Patients

In combination with other antiretrovirals, tenofovir disoproxil fumarate/TDF (Viread) is FDA-approved for the treatment of HIV infection. However, controlled data are sparse on the long-term renal (kidney) tolerability of TDF at the approved daily dose of 300 mg in treatment-naive HIV patients.

The current 144-week, 600-patient, multicenter, randomized, double-blind, placebo controlled trial compared stavudine [Zerit] (301 patients) and TDF (299 patients), both administered in combination with lamivudine (Epivir) and efavirenz (Sustiva), in antiretroviral-naive patients. All medications were taken orally.

At baseline, all patients had serum creatinines <1.5 mg/dl, calculated creatinine clearances >/=60 ml/min and a serum phosphorus >/=2.2 mg/dl.

Results

The incidences of grades 1 (>/=0.5 mg/dl increase from baseline), 2 (2.1-3.0 mg/dl) and 3 (3.1-6.0 mg/dl) serum creatinine elevations at week 144 were 4, <1 and 0%, respectively, in the TDF group and 2, 0 and <1% in the stavudine control group (P = NS).

There were no grade 4 (>6 mg/dl) serum creatinine elevations.

At week 144, there was no change from baseline in the mean (0.83 mg/dl) serum creatinine in the TDF group compared with a 0.1 mg/dl decrease from baseline (0.83 mg/dl) in the stavudine control group.

The incidences of grades 1 (2.0-2.2 mg/dl), 2 (1.5-1.9 mg/dl) and 3 (1.0-1.4 mg/dl) hypophosphataemia at week 144 were 4, 3 and <1%, respectively, in the TDF group and 4, 2 and <1% in the control group (P = NS).

No patient experienced grade 4 (<1.0 mg/dl) hypophosphataemia.

At week 144, the decrease of mean serum phosphorus levels from baseline in both groups was similar.

No patient developed Fanconi's syndrome or proximal renal tubular dysfunction during the study.

Conclusion

The authors conclude, “Through 144 weeks, TDF and stavudine, each administered in combination with efavirenz and lamivudine, had similar renal safety profiles in treatment-naive HIV-infected patients with normal renal function at baseline.”

Department of Nephrology, Pitie-Salpetriere Hospital, Paris, France.

See also Tenofovir Nephrotoxicity Seems Rare, Is Reversible and Risk Factors May Include Combination with Ritonavir and Pre-existing Renal Insufficiency

03/16/05

Reference
H Izzedine and others. Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naïve HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study. Nephrology, Dialysis, and Transplantation. March 1, 2005. [Epub ahead of print]

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