Bone Mineral Density and Fractures in Antiretroviral-Naive Persons Randomized to Receive Abacavir-Lamivudine or Tenofovir Disoproxil Fumarate-Emtricitabine Along With Efavirenz or Atazanavir-Ritonavir: AIDS Clinical Trials Group A5224s, a Substudy of ACTG A5202

• Published in: The Journal of infectious diseases Vol. 203; no. 12; pp. 1791 - 1801
• Main Authors: McComsey, Grace A., Kitch, Douglas, Daar, Eric S., Tierney, Camlin, Jahed, Nasreen C., Tebas, Pablo, Myers, Laurie, Melbourne, Kathleen, Ha, Belinda, Sax, Paul E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.06.2011
• Series: Editor's Choice
• Subjects: Absorptiometry, Photon; Adenine - adverse effects; Adenine - analogs & derivatives; Adult; Anti-HIV Agents - adverse effects; Antiretroviral Therapy, Highly Active - adverse effects; Arm; Arts; Atazanavir Sulfate; Benzoxazines - adverse effects; Biological and medical sciences; Bone density; Bone Density - drug effects; Bone fractures; Bones; CD4 Lymphocyte Count; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Dideoxynucleosides - adverse effects; Drug Combinations; Drug Therapy, Combination; Emtricitabine; Female; Fractures, Bone - chemically induced; Fractures, Bone - epidemiology; Fundamental and applied biological sciences. Psychology; Hip; HIV 1; HIV Infections - complications; HIV Infections - drug therapy; HIV/AIDS; Human viral diseases; Humans; Infectious diseases; Intention to Treat Analysis; Lamivudine - adverse effects; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Oligopeptides - adverse effects; Organophosphonates - adverse effects; Osteoporosis - chemically induced; Percentage change; Pyridines - adverse effects; Risk Factors; Ritonavir - adverse effects; RNA; Spine; Tenofovir; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Purine nucleoside; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Ritonavir; Non nucleoside compound; Diseases of the osteoarticular system; Fracture; Nucleotide analog; Efavirenz; Osteoarticular system; Tenofovir; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Clinical trial; Pyrimidine nucleoside; Emtricitabine; Human; Immunopathology; Purine nucleotide; Acyclic nucleotide; Atazanavir; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; AIDS; Organic phosphonate; Immune deficiency; Trauma; Infection; Allosteric inhibitor; Peptidases; Nucleotidyltransferases; Dideoxynucleoside; Viral disease; Abacavir; Hydrolases; Bone; Protease inhibitor
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir188

Background. Long-term effects of abacavir (ABC)-lamivudine (3TC), compared with tenofovir (TDF)-emtricitabine (FTC) with efavirenz (EFV) or atazanavir plus ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed. Methods. A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intent-to-treat. Statistical tests used the factorial design and included linear regression, 2-sample t, log-rank, and Fisher's exact tests. Results. Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non- Hispanic; the median HIV-1 RNA load was 4.6 log₁₀ copies/ML, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/μL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P = .004) and -2.6% and -4.0% (P = .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P = .035) and -3.1% and -3.4% (P = .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components. Conclusions. Compared with ABC-3TC, TDF-FTC-treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.