[WeOrB1266] Tenofovir DF: A 48-week final analysis from a phase III randomized, double blind, placebo controlled study in antiretroviral treatment experienced patients (study 907)

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Tenofovir DF: A 48-week final analysis from a phase III randomized, double blind, placebo controlled study in antiretroviral treatment experienced patients (study 907)

[AUTHOR(S):] A L Pozniak¹, A Plettenberg², W Rozenbaum³, A Sonnerborg⁴, J M Molina⁵, J Gatell⁶, S S Chen⁷, B P Kearney⁸, M D Miller, Coakley,D.F., Cheng,A.

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. WeOrB1266

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 (≥ 8 wks) background antiretroviral therapy (ART). Single dose (day 1) and long term pharmacokinetics (PK) were assessed in a subset of patients. 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. Tenofovir PK were unchanged over 12, 24, 36 or 48 weeks of dosing compared to Day 1 (mean AUC = 2.8 µg hr/mL) (p > 0.37) and no evidence of drug related renal toxicity was observed. Through 48 weeks, 3% (n=8) of patients developed the tenofovir-associated K65R resistance mutation.

	Placebo	Tenofovir DF	Tenofovir DF
	24 Weeks	24 Weeks	48 Weeks
	n = 182	n = 368	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 Adverse Events (%)	14	14	20
≥ Grade 3 Laboratory Abnormalities (%)	38	25	35

CONCLUSIONS: Through 48 weeks, once daily tenofovir DF 300 mg provides durable antiviral suppression in treatment experienced patients with an unchanged PK and a safety profile which remains similar to placebo.

Presenting author: A L Pozniak

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1Chelsea and Westminster Hospital, United Kingdom

2IFI Institut, Hamburg, Germany

3Rothschild Hospital, Paris, France

4Huddinge University Hospital, Huddinge, Sweden

5Saint-Louis Hospital, Paris, France

6Hospital Clinic, Barcelona, Spain

7Gilead Sciences, Foster City, CA, United States

8Gilead Sciences, Foster City, CA, United States

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