A Randomized Comparative Trial of Continued Abacavir/Lamivudine plus Efavirenz or Replacement with Efavirenz/Emtricitabine/Tenofovir DF in Hypercholesterolemic HIV-1 Infected Individuals

• Published in: PloS one Vol. 10; no. 2; p. e0116297
• Main Authors: Moyle, Graeme J., Orkin, Chloe, Fisher, Martin, Dhar, Jyoti, Anderson, Jane, Wilkins, Edmund, Ewan, Jacqueline, Ebrahimi, Ramin, Wang, Hui
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.02.2015; Public Library of Science (PLoS)
• Subjects: Abacavir; Acquired immune deficiency syndrome; Adult; AIDS; Alkynes; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Benzoxazines - administration & dosage; Benzoxazines - adverse effects; Blood cholesterol; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Cholesterol - blood; Comparative analysis; Comparative studies; Cyclopropanes; Dideoxynucleosides - administration & dosage; Dideoxynucleosides - adverse effects; Drug Combinations; Efavirenz; Emtricitabine; Emtricitabine - administration & dosage; Emtricitabine - adverse effects; Female; Follow-Up Studies; Health risks; High density lipoprotein; Highly active antiretroviral therapy; HIV; HIV Infections - blood; HIV Infections - complications; HIV Infections - drug therapy; HIV-1; Human immunodeficiency virus; Humans; Hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - complications; Hypercholesterolemia - drug therapy; Lamivudine; Lamivudine - administration & dosage; Lamivudine - adverse effects; Lipids; Lipoproteins (high density); Lipoproteins (low density); Low density lipoprotein; Low density lipoproteins; Male; Middle Aged; Randomization; Tenofovir; Tenofovir - administration & dosage; Tenofovir - adverse effects; Therapy; Trans fatty acids; Triglycerides; United Kingdom > UK; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0116297

Drug choice and metabolic changes with antiretroviral therapy contribute to cardiovascular risk in persons with HIV-1 infection. 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. 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). Switching from ABC/3TC+EFV to EFV/FTC/TDF in persons with hypercholesterolemia maintains virological control and significantly improves key lipid parameters. ClinicalTrials.gov NCT00615810.