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Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and Safety of Tenofovir DF vs Stavudine in Combination Therapy in Antiretroviral-Naive Patients: A 3-Year Randomized Trial. JAMA. 2004;292(2):191–201. doi:10.1001/jama.292.2.191
Author Affiliations: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Md (Dr Gallant); Department of Internal Medicine, University Hospital, J.W. Goethe-Universität, Frankfurt, Germany (Dr Staszewski); Department of Genitourinary Medicine, Chelsea and Westminster Hospital, London, England (Dr Pozniak); Infectious Disease Consultants Research Initiative, Altamonte Springs, Fla (Dr DeJesus); Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil (Dr Suleiman); and Gilead Sciences, Foster City, Calif (Drs Miller, Coakley, Lu, Toole, and Cheng).
Context Tenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue
reverse transcriptase inhibitor.
Objective To evaluate the efficacy and safety of tenofovir DF compared with stavudine
in antiretroviral-naive patients.
Design, Setting, and Participants A prospective, randomized, double-blind study conducted at 81 centers
in the United States, South America, and Europe from June 9, 2000, to January
30, 2004. A total of 753 patients infected with HIV who were antiretroviral
naive were screened and 602 patients entered the study.
Intervention Patients were randomized to receive either tenofovir DF (n = 299) or
stavudine (n = 303), with placebo, in combination with lamivudine and efavirenz.
Main Outcome Measure Proportion of patients with HIV RNA levels of less than 400 copies/mL
at week 48.
Results In the primary intent-to-treat analysis in which patients with missing
data or who added or switched antiretroviral medications before week 48 were
considered as failures, the proportion of patients with HIV RNA of less than
400 copies/mL at week 48 was 239 (80%) of 299 in patients receiving tenofovir
DF and 253 (84%) of 301 in patients receiving stavudine (95% confidence interval,
−10.4% to 1.5%), exceeding the predefined −10% limit for equivalence.
However, equivalence was demonstrated in the secondary analyses (HIV RNA <50
copies/mL) at week 48 and through 144 weeks. Virologic failure was associated
most frequently with efavirenz and lamivudine resistance. Through 144 weeks,
the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine
groups, respectively (P = .06). A more favorable
mean change from baseline in fasting lipid profile was noted in the tenofovir
DF group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n
= 170] vs +134 mg/dL for stavudine [n = 162], P<.001),
total cholesterol (+30 mg/dL [n = 170] vs +58 mg/dL [n = 162], P<.001), direct low-density lipoprotein cholesterol (+14 mg/dL [n
= 169] vs +26 mg/dL [n = 161], P<.001), and high-density
lipoprotein cholesterol (+9 mg/dL [n = 168] vs +6 mg/dL [n = 154], P = .003). Investigator-reported lipodystrophy was less common in the
tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58
[19%] of 301, P<.001). The number of bone fractures
and the renal safety profile were similar between the 2 groups.
Conclusions Through 144 weeks, the combination of tenofovir DF, lamivudine, and
efavirenz was highly effective and comparable with stavudine, lamivudine,
and efavirenz in antiretroviral-naive patients. However, tenofovir DF appeared
to be associated with better lipid profiles and less lipodystrophy.
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