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.
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.
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.
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: firstname.lastname@example.org).