Background: TDF is a single tablet, once daily nucleotide analog reverse transcriptase inhibitor with potent activity against wild-type and nucleoside resistant HIV. Study 903 was designed to evaluate the efficacy and safety of TDF as part of a fixed ART regimen in antiretroviral naïve patients over 144 weeks. 

 

Methods:  Phase III, multicenter, randomized, double-blind, active-controlled trial in patients with HIV-1 RNA > 5,000 copies/mL with no requirement for entry CD4+ lymphocyte cell count.  Patients were randomized to receive either TDF (300mg qd) or d4T (40mg bid) plus 3TC (150mg bid) and EFV (600mg qd). Patients randomized to TDF received d4T placebo bid while those randomized to d4T received TDF placebo once daily.

 

Results: The intent-to-treat (ITT) population included 600 patients with the following baseline characteristics: mean age 36 years, 26% female, 36% non-Caucasian, mean HIV-1 RNA 4.9 log₁₀ c/mL; mean CD4 count 279 cells/mm³. Data from a week 96 preliminary interim analysis are shown below.

 

Week 96 Results	TDF/ 3TC/EFV		d4T/ 3TC/EFV		95% CI*
HIV RNA <400 c/mL
Missing equals failure	82%		78%		-3, +10
Missing values excluded	96%		93%		+1, +8
HIV RNA <50 c/mL
Missing equals failure	78%		74%		-3, +11
Missing values excluded	92%		88%		0, +10
Mean Change CD4 cell count (cells/mm3)	+261		+266
Study Discontinuation	14%		15%
³ Grade 3 Adverse Events	23%		23%
³ Grade 3 Laboratory Abnormalities	34%		39%
Mean Increase Fasting Triglycerides (mg/dL)**	4		104
Mean Increase Fasting Total Cholesterol (mg/dL)**	30		52
Mean Increase Fasting LDL Cholesterol (mg/dL)**	11		20
Mean Increase Fasting HDL Cholesterol (mg/dL)***	9		7

*For difference in TDF arm – d4T arm ** p-value < 0.001 *** p-value = 0.028

 

Conclusions: Through 96 weeks, combination therapy with TDF was comparable to d4T for efficacy and safety in ART-naïve patients. Patients in the TDF arm had differences in cholesterol (total, LDL and HDL) and triglycerides which were statistically significant compared to the d4T arm.