A randomized comparative trial of continued zidovudine/lamivudine or replacement with tenofovir disoproxil fumarate/emtricitabine in efavirenz-treated HIV-1-infected individuals.
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.
Fisher
Martin
M
Elton John Centre, Brighton and Sussex University Hospitals, Brighton, United Kingdom.
Moyle
Graeme J
GJ
Shahmanesh
Mohsen
M
Orkin
Chloe
C
Kingston
Margaret
M
Wilkins
Edmund
E
Ewan
Jacqueline
J
Liu
Hui
H
Ebrahimi
Ramin
R
Reilly
Geraldine
G
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D048588:Benzoxazines / Q000008:administration & dosage; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068679:Emtricitabine; D005121:Extremities; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage; D000068698:Tenofovir; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D008055:Lipids; D063065:Organophosphonates; D003841:Deoxycytidine; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz