A randomized comparative trial of continued abacavir/lamivudine plus efavirenz or replacement with efavirenz/emtricitabine/tenofovir DF in hypercholesterolemic HIV-1 infected individuals

PLoS One. 2015 Feb 6;10(2):e0116297. doi: 10.1371/journal.pone.0116297. eCollection 2015.

Abstract

Background: Drug choice and metabolic changes with antiretroviral therapy contribute to cardiovascular risk in persons with HIV-1 infection.

Methods: A randomized, 12 week, open-label, comparative study of the impact on lipids of continuation of abacavir/lamivudine (ABC/3TC) plus efavirenz (EFV) or replacement with the single tablet regimen of EFV/emtricitabine/tenofovir DF (EFV/FTC/TDF) in hypercholesterolaemic subjects on successful antiretroviral therapy, with a 12-week extension with all subjects on EFV/FTC/TDF.

Results: 157 subjects received study drug, 79 switched to EFV/FTC/TDF and 78 subjects continued ABC/3TC+EFV. At Week 12, 73 subjects on ABC/3TC+EFV switched to EFV/FTC/TDF. The switch was well tolerated and no subject experienced viral rebound. Median baseline fasting total cholesterol was 6.32 mmol/L. 12 weeks following switch, the difference in the means (LSM) between treatment groups (EFV/FTC/TDF minus ABC/3TC+EFV) in total cholesterol change from baseline was -0.74 mmol/l (95% CI -1.00, -0.47, p < 0.001). The median change from baseline in total cholesterol following switch in the EFV/FTC/TDF arm was -0.86 mmol/l (p < 0.001) compared with +0.01 mmol/l (p = 0.45) in the continuation arm at Week 12. Significant (p < 0.001) differences between treatment groups following switch were seen for all lipid fractions from baseline to Week 12: LDL cholesterol (-0.47 mmol/L [-0.70, -0.25]), HDL cholesterol (-0.15 mmol/L [-0.21, -0.08]), triglycerides (-0.43 mmol/L [-0.75, -0.11]), and non HDL cholesterol (-0.56 mmol/L [-0.80, -0.31]). In the extension phase, similar declines in total cholesterol were observed with a median change from Week 12 to Week 24 of -0.73 mmol/L (p < 0.001).

Conclusions: Switching from ABC/3TC+EFV to EFV/FTC/TDF in persons with hypercholesterolemia maintains virological control and significantly improves key lipid parameters.

Trial registration: ClinicalTrials.gov NCT00615810.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkynes
  • Benzoxazines / administration & dosage*
  • Benzoxazines / adverse effects
  • Cholesterol / blood
  • Cyclopropanes
  • Dideoxynucleosides / administration & dosage*
  • Dideoxynucleosides / adverse effects
  • Drug Combinations
  • Emtricitabine / administration & dosage*
  • Emtricitabine / adverse effects
  • Female
  • Follow-Up Studies
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy*
  • Lamivudine / administration & dosage*
  • Lamivudine / adverse effects
  • Male
  • Middle Aged
  • Tenofovir / administration & dosage*
  • Tenofovir / adverse effects

Substances

  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Dideoxynucleosides
  • Drug Combinations
  • abacavir, lamivudine drug combination
  • Lamivudine
  • Cholesterol
  • Tenofovir
  • Emtricitabine
  • efavirenz

Associated data

  • ClinicalTrials.gov/NCT00615810

Grants and funding

Gilead Sciences are the Sponsor and funders of this study. Gilead designed the study with input from the lead investigators. Gilead collected and analysed the data, made the decision to publish and reviewed and commented on the manuscript. The authors on this manuscript were Principal Investigators on this clinical trial and as such their institutions were paid a per patient fee for the work they performed and they were each paid travel expenses to attend study meetings. Dr Moyle, Dr Fisher and Dr Orkin presented the study on Gilead’s behalf at International conferences and as such were supported to attend the conferences.