Background: Tenofovir DF (TDF) is a single tablet, once-daily nucleotide reverse transcriptase inhibitor with potent activity against wild-type and nucleoside resistant HIV.

Methods: Multi-center, international, double blind, randomized study of 550 treatment-experienced patients with HIV RNA between 400 and 10,000 copies/mL, who received TDF 300 mg or placebo for 24 weeks in addition to stable (at 8 weeks) background antiretroviral therapy (ART).  After week 24, all patients received open label TDF 300 mg through 48 weeks.

Results: Mean baseline HIV and demographic characteristics: HIV RNA 4457 copies/mL; CD4 cell count 427 cells/mm³ ; prior ART use 5.4 years; male (85%); Caucasian (69%) and approximately 41 years old.  253 patients were randomly assigned to a virology substudy; baseline resistance mutations were 94% NRTI, 58% PI, and 48% NNRTI.  Through 48 weeks, 3% of patients developed the tenofovir-associated K65R resistance mutation.  No evidence of drug related renal toxicity was observed through 48 weeks.

	Placebo   24 weeks     n= 182	TDF  24 weeks    n= 368	TDF  48 weeks    n=368
DAVG HIV RNA (log10 copies/mL)	-0.03	-0.61	-0.57
HIV RNA <400 (%)	13	45	41
HIV RNA <50 (%)	1	22	18
DAVG CD4 Count (cells/mm3)	-11	+13	+13
Study Drug Discontinuation (%)	6	6	12
Grade 3/4 Adverse Events (%)	14	14	20
Grade 3/4 Lab Abnormalities (%)	38	25	35

               

Conclusions: Through 48 weeks, once-daily tenofovir DF 300 mg provides

durable antiviral suppression in treatment experienced patients.  In addition,

tenofovir DF has a safety profile which remains similar to placebo.