The Body Covers: The 39th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy
Session 93.I: Late-Breaker Slide Session II
September 27, 1999
Abstract: A Double-Blind, Placebo-Controlled Study of Tenofovir Disoproxil Fumarate (TDF) for the Treatment of HIV Infection (Paper LB-19)
Tenofovir disoproxil fumarate (TDF), formerly known as PMPA, is a nucleotide analogue with potent activity in vitro against HIV and SIV. Patients in the phase I study 901 had a dose-related drop in viral load. Study 902 was done in patients on stable HAART regimens for >8 weeks with <4 drugs. Patients had CD4 counts ~500, with mean HIV RNA ~5000 copies. The mean time on ARV therapy was ~4.5 years.
187 patients were studied, 94% of whom were resistant to AZT, 3TC or both. 50% had PI resistance and 20% showed NNRTI resistance. No change was noted in the placebo group. Patient receiving TDF had a dose related decrease in viral load. The peak drop on the 300 mg arm was 0.8 logs sustained for 24 weeks. Patients were allowed to change background therapy at 12 weeks.
There were few toxicities noted. There was no major difference in grade 3 or 4 toxicities between the placebo group and the treatment group. The most frequent laboratory AE was an increase in triglycerides, noted in patients on PIs. Because of the known renal toxicity of adefovir, the only other well-studied nucleotide analogue, renal function was assessed. One patient had an increase from baseline. There was no evidence of progressive nephrotoxicity. There was also no evidence of phosphate wasting, another characteristic of adefovir-related proximal renal tubular dysfunction.
This is definitely a drug-in-development to watch, as it may be useful against multiply-resistant viruses. There is currently a compassionate expanded access protocol in development, which will provide 300 slots for patients with low CD4 counts who have no other options (it is being run in tandem with a similar program for ABT-378).
Authored by: R. Schooley, et al.
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