Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.
BACKGROUND
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.


METHODS
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.


METHODS
Patients were randomized to receive either tenofovir DF (n = 299) or stavudine (n = 303), with placebo, in combination with lamivudine and efavirenz.


METHODS
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.
Gallant
Joel E
JE
Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Md 21287, USA. jgallant@jhmi.edu
Staszewski
Schlomo
S
Pozniak
Anton L
AL
DeJesus
Edwin
E
Suleiman
Jamal M A H
JM
Miller
Michael D
MD
Coakley
Dion F
DF
Lu
Biao
B
Toole
John J
JJ
Cheng
Andrew K
AK
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D003521:Cyclopropanes; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D010078:Oxazines / Q000627:therapeutic use; D011446:Prospective Studies; D018119:Stavudine / Q000627:therapeutic use*; D000068698:Tenofovir; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010078:Oxazines; D019259:Lamivudine; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine; C098320:efavirenz