Comparison of Changes in Bone Density and Turnover with Abacavir-Lamivudine versus Tenofovir-Emtricitabine in HIV-Infected Adults: 48-Week Results from the ASSERT Study

• Published in: Clinical infectious diseases Vol. 51; no. 8; pp. 963 - 972
• Main Authors: Stellbrink, Hans-Jürgen, Orkin, Chloe, Arribas, Jose Ramon, Compston, Juliet, Gerstoft, Jan, Van Wijngaerden, Eric, Lazzarin, Adriano, Rizzardini, Giuliano, Sprenger, Herman G., Lambert, John, Sture, Gunta, Leather, David, Hughes, Sara, Zucchi, Patrizia, Pearce, Helen
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.10.2010; University of Chicago Press; Oxford University Press
• Subjects: Absorptiometry, Photon; Acquired immune deficiency syndrome; Adenine - administration & dosage; Adenine - adverse effects; Adenine - analogs & derivatives; Adolescent; Adult; Aged; AIDS; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretrovirals; Antiviral agents; Biological and medical sciences; Biological markers; Body mass index; Bone and Bones - pathology; Bone and Bones - physiopathology; Bone density; Bone Density - drug effects; Bone Density - physiology; Bones; Comparative analysis; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Dideoxynucleosides - administration & dosage; Dideoxynucleosides - adverse effects; Drug Combinations; Drug therapy; Emtricitabine; Europe; Female; Hip; Hip fractures; HIV; HIV Infections - drug therapy; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Investigative techniques, diagnostic techniques (general aspects); Lamivudine - administration & dosage; Lamivudine - adverse effects; Lumbar spine; Male; Medical sciences; Middle Aged; Organophosphonates - administration & dosage; Organophosphonates - adverse effects; Osteoarticular system. Muscles; Pharmacology. Drug treatments; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Tenofovir; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Europe; Purine nucleoside; Antiretroviral agent; RNA-directed DNA polymerase; Nucleotide analog; Tenofovir; Reverse transcriptase inhibitor; Nucleoside analog; Adult; Antiviral; Pyrimidine nucleoside; Human; Emtricitabine; Immunopathology; Purine nucleotide; Acyclic nucleotide; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; AIDS; Organic phosphonate; Immune deficiency; Infection; Nucleotidyltransferases; Dideoxynucleoside; Viral disease; Abacavir; Bone mineral density; Comparative study
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1086/656417

Background. Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles. Methods. In this European, multicenter, open-label, 96-week study, antiretroviral-naive adult subjects with human immunodeficiency virus (HIV) infection were randomized to receive either abacavir-lamivudine or tenofovir-emtricitabine with efavirenz. Primary analyses were conducted after 48 weeks of treatment. Bone mineral density (BMD), a powered secondary end point, was assessed by dual energy x-ray absorptiometry. Bone turnover markers (osteocalcin, procollagen 1 N-terminal propeptide, bone specific alkaline phosphatase, and type 1 collagen cross-linked C telopeptide [CTx]) were assessed in an exploratory analysis. Results. A total of 385 subjects were enrolled in the study. BMD loss was observed in both treatment groups, with a significant difference in the change from baseline in both total hip (abacavir-lamivudine group, −1.9%; tenofovir-emtricitabine group, −3.6%; P <; .001) and lumbar spine (abacavir-lamivudine group, −1.6%; tenofoviremtricitabine group, −2.4%; P = .036). BMD loss of ⩾6% was more common in the tenofovir-emtricitabine group (13% of the tenofovir-emtricitabine group vs 3% of the abacavir-lamivudine group had a loss of ⩾6% in the hip; 15% vs 5% had a loss of ⩾6% in the spine). Bone turnover markers increased in both treatment groups over the first 24 weeks, stabilizing or decreasing thereafter. Increases in all markers were significantly greater in the tenofovir-emtricitabine treatment group than in the abacavir-lamivudine group at week 24. All but CTx remained significantly different at week 48 (eg, osteocalcin: abacavir-lamivudine group, +8.07 mg/L; tenofoviremtricitabine group, +11.92 mg/L; P < .001). Conclusions. This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine.