A randomized comparative trial of continued zidovudine/lamivudine or replacement with tenofovir disoproxil fumarate/emtricitabine in efavirenz-treated HIV-1-infected individuals

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 51; no. 5; p. 562
• Main Authors: Fisher, Martin, Moyle, Graeme J, Shahmanesh, Mohsen, Orkin, Chloe, Kingston, Margaret, Wilkins, Edmund, Ewan, Jacqueline, Liu, Hui, Ebrahimi, Ramin, Reilly, Geraldine
• Format: Journal Article
• Language: English
• Published: United States 01.08.2009
• Subjects: Adenine - administration & dosage; Adenine - analogs & derivatives; Adipose Tissue - drug effects; Adipose Tissue - pathology; Adult; Aged; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Benzoxazines - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Emtricitabine; Extremities; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - pathology; HIV Infections - virology; HIV-1; HIV-Associated Lipodystrophy Syndrome - etiology; HIV-Associated Lipodystrophy Syndrome - metabolism; HIV-Associated Lipodystrophy Syndrome - pathology; Humans; Lamivudine - administration & dosage; Lipids - blood; Male; Middle Aged; Organophosphonates - administration & dosage; Tenofovir; Young Adult; Zidovudine - administration & dosage
• ISSN: 1525-4135
• DOI: 10.1097/QAI.0b013e3181ae2eb9

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.