96-Week results of abacavir/lamivudine versus tenofovir/emtricitabine, plus efavirenz, in antiretroviral-naive, HIV-1-infected adults: ASSERT study

• Published in: Antiviral therapy Vol. 18; no. 7; pp. 905 - 913
• Main Authors: MOYLE, Graeme J, STELLBRINK, Hans-Jürgen, COMPSTON, Juliet, ORKIN, Chloe, ARRIBAS, José R, DOMINGO, Pere, GRANIER, Catherine, PEARCE, Helen, SEDANI, Sangeeta, GARTLAND, Martin
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2013
• Subjects: Adenine - analogs & derivatives; Adenine - therapeutic use; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active - adverse effects; Antiviral agents; Benzoxazines - therapeutic use; Biological and medical sciences; Bone and Bones - drug effects; Bone and Bones - pathology; Bone Density; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Dideoxynucleosides - therapeutic use; Drug Combinations; Emtricitabine; Female; Glomerular Filtration Rate - drug effects; HIV Infections - drug therapy; HIV Infections - virology; HIV-1; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Kidney - drug effects; Kidney - physiopathology; Lamivudine - therapeutic use; Male; Medical sciences; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Tenofovir; Time Factors; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Purine nucleoside; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Non nucleoside compound; Nucleotide analog; Efavirenz; Result; Tenofovir; Reverse transcriptase inhibitor; Nucleoside analog; Adult; Antiviral; Pyrimidine nucleoside; Human; Emtricitabine; Immunopathology; Purine nucleotide; Drug combination; Acyclic nucleotide; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; AIDS; Organic phosphonate; Immune deficiency; Infection; Allosteric inhibitor; Nucleotidyltransferases; Dideoxynucleoside; Viral disease; Abacavir; Comparative study
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/imp2667

Abacavir/lamivudine (ABC/3TC) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) are widely used as first-line antiretroviral therapies. However, there are limited data comparing the safety of these therapies with long-term use. The objective of this study was to assess the long-term safety of these commonly used first-line nucleoside/nucleotide combinations each administered with efavirenz (EFV). This open-label, 96-week, randomized study compared the safety (renal, bone and metabolic) and efficacy of ABC/3TC and TDF/FTC plus EFV in HLA-B*5701-negative antiretroviral-naive adults. A total of 385 subjects were enrolled, and 249 (65%) subjects completed the study. The difference in changes from baseline in estimated glomerular filtration rate (calculated by the Modified Diet in Renal Disease equation) between treatment arms was not significant. There was a significant difference between the arms (P < 0.0001) for markers of tubular dysfunction (retinol-binding protein and ß-2 microglobulin) favouring ABC/3TC. Hip bone mineral density decreased from baseline in both arms, with a significantly greater decline with TDF/FTC (ABC/3TC -2.2% and TDF/FTC -3.5%; P < 0.001 at week 96). Subjects in the ABC/3TC arm had greater increases from baseline in median total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides. Adverse events were similar between arms. The virological failure rate was low in both arms. ABC/3TC and TDF/FTC in combination with EFV minimally affected estimated glomerular filtration rate over 96 weeks. TDF/FTC was associated with greater increases in tubular dysfunction and bone turnover marker levels, greater decreases in hip bone mineral density, and smaller increases in serum lipid levels.