Simplification of Antiretroviral Therapy with Tenofovir‐Emtricitabine or Abacavir‐Lamivudine: A Randomized, 96‐Week Trial
1National Centre in HIV Epidemiology and Clinical Research UNSW, 2Holdsworth House Medical Practice, 3East Sydney Doctors, 4St Vincent’s Hospital, and 5St Vincent's Centre for Applied Medical Research, Sydney, Australia
Background.
There are 2 once‐daily, fixed‐dose‐combination, dual–nucleoside analogue tablets: tenofovir 300 mg–emtricitabine 200 mg (TDF‐FTC) and abacavir 600 mg–lamivudine 300 mg (ABC‐3TC). Which fixed‐dose‐combination tablet is more effective and safe is uncertain.
Methods.We compared TDF‐FTC and ABC‐3TC in a randomized, open‐label, 96‐week trial in which either fixed‐dose‐combination was substituted for current nucleoside treatments in human leukocyte antigen–B*5701–negative adults with human immunodeficiency virus loads <50 copies/mL. The primary end point was virological failure (consecutive viral load measurements >400 copies/mL, by intention‐to‐treat). Secondary end points included death, AIDS, adverse events, serious non‐AIDS events, metabolic parameters, and body composition. We used exact statistics for differences in proportions, T tests to compare means, and Cox regression for hazard ratios.
Results.Of 441 patients who were screened, 357 were treated; 98% were men, the mean age was 45 years, 30% were receiving TDF, 20% were receiving ABC, and 24% were receiving a protease inhibitor. Virological failure was uncommon (5.6% for ABC‐3TC and 3.9% for TDF‐FTC; difference, 1.7%; 95% confidence interval [CI], −2.8% to 6.1%; 
). No participant developed AIDS, whereas 18 (5%) participants developed a serious non‐AIDS event (rate, 2.79 events per 100 person‐years; 95% CI, 1.76–4.43), of which 4 were fatal. TDF‐FTC was associated with significantly fewer serious non‐AIDS events than ABC‐3TC (1.2 vs 4.8 events per 100 patient‐years; hazard ratio [HR], 0.24; 95% CI, 0.08–0.73; 
), influenced mostly by a lower rate of cardiovascular events (0.3 vs 2.2 events per 100 patient‐years; HR, 0.12; 95% CI, 0.02–0.98; 
). TDF‐FTC resulted in significantly lower bone mineral density (mean difference in hip t score, 0.16; 95% CI, 0.08–0.23; 
) but not in more fractures.
Conclusions.In this population, TDF‐FTC and ABC‐3TC had similar virological efficacy, but ABC‐3TC was associated with more serious non‐AIDS events, particularly cardiovascular events.
Clinical trials registration.NCT00192634.
Received 26 March 2009; accepted 24 June 2009; electronically published 20 October 2009.
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(See the editorial commentary by Reiss, on pages 1602–4.)
Cited by
Online publication date: 15-Nov-2009.
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Presented in part: 16th Conference on Retroviruses and Opportunistic Infections, Montreal, Canada, February 2009 (poster 576).
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aMembers of the study group are listed at the end of the text.