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A Randomized Comparative Trial of Continued Zidovudine/Lamivudine or Replacement With Tenofovir Disoproxil Fumarate/Emtricitabine in Efavirenz-Treated HIV-1-Infected Individuals

Fisher, Martin FRCP*; Moyle, Graeme J MD, MBBS; Shahmanesh, Mohsen FRCP; Orkin, Chloe MRCP§; Kingston, Margaret FRCP; Wilkins, Edmund FRCP; Ewan, Jacqueline BSc (Hons)#; Liu, Hui PhD#; Ebrahimi, Ramin MS#; Reilly, Geraldine RN#for the SWEET (Simplification With Easier Emtricitabine Tenofovir) group UK

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 2009 - Volume 51 - Issue 5 - p 562-568
doi: 10.1097/QAI.0b013e3181ae2eb9
Clinical Science

Background: Long-term antiretroviral therapy dramatically reduces HIV-related morbidity and mortality but is also associated with metabolic and morphological changes and requires high levels of adherence.

Methods: A randomized, 48-week, open-label, comparative study of continuation of twice-daily zidovudine/lamivudine or replacement with once-daily tenofovir disoproxil fumarate/emtricitabine in individuals on successful efavirenz-based antiretroviral therapy. Limb fat mass was assessed by dual x-ray absorptiometry in a subset of participants through week 48.

Results: Two hundred thirty-four individuals were randomized and treated (117 each to continue or switch) with 206 subjects completing 48 weeks of study. Five percent subjects in the continue group and 3% subjects in the switch group discontinued due to adverse events. By intent-to-treat, missing = failure analysis, no differences in virological efficacy were observed at any time point (week 48 <50 copies/mL continue 85%, switch 88%). At week 24, switching was associated with significant increases in hemoglobin (mean difference 0.37 g/dL, 95% confidence interval: 0.15 to 0.58 g/dL, P < 0.001) and significant declines in total cholesterol and triglycerides. In the dual x-ray absorptiometry substudy (n = 100), fat was preserved or increased in the switch group but declined in the continue group (mean difference 448 g, 95% confidence interval: 57 to 839 g, P = 0.025). Individuals with longer exposure to zidovudine and lower baseline limb fat experienced less limb fat increase after switching. No differences in renal adverse events were observed between groups.

Conclusions: Switching from zidovudine/lamivudine to tenofovir disoproxil fumarate/emtricitabine in persons on efavirenz therapy maintains virological control, establishes a once-daily regimen, results in improvements in hemoglobin and key lipid parameters, and preserves and restores limb fat relative to continuation of zidovudine/lamivudine.

From the *Elton John Centre, Brighton and Sussex University Hospitals, Brighton, United Kingdom; †St. Stephen's Centre, Chelsea and Westminster Hospital, London, United Kingdom; ‡Department of Genitourinary Medicine, Selly Oak Hospital, Birmingham, United Kingdom; §Department of Genitourinary Medicine, St. Bartholemew's and Royal London Hospitals, London, United Kingdom; Department of Genitourinary Medicine, Manchester Royal Infirmary, Manchester, United Kingdom; ¶Department of Infectious Diseases, North Manchester General Hospital, Manchester, United Kingdom; and #Gilead Sciences, Foster City, CA.

Received for publication September 7, 2008; accepted January 13, 2009.

ClinicalTrials.gov Identifier NCT00323544.

Members of SWEET group have been listed in Appendix 1.

Correspondence to: Dr. Graeme J. Moyle, MD, MBBS, Chelsea and Westminster Hospital, 369 Fulham Rd, London SW10 9NH, United Kingdom (e-mail: gm@moyleg.demon.co.uk).

© 2009 Lippincott Williams & Wilkins, Inc.