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

TitleBone 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
Publication TypeJournal Article
Year of Publication2011
AuthorsMcComsey GA, Kitch D, Daar ES, Tierney C, Jahed NC, Tebas P, Myers L, Melbourne K, Ha B, Sax PE
JournalJ Infect Dis
Volume203
Issue12
Pagination1791-801
Date Published2011 Jun 15
ISSN1537-6613
KeywordsAbsorptiometry, Photon, Adenine, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Atazanavir Sulfate, Benzoxazines, Bone Density, CD4 Lymphocyte Count, Deoxycytidine, Dideoxynucleosides, Drug Combinations, Drug Therapy, Combination, Emtricitabine, Female, Fractures, Bone, HIV Infections, Humans, Intention to Treat Analysis, Lamivudine, Male, Middle Aged, Oligopeptides, Organophosphonates, Osteoporosis, Pyridines, Risk Factors, Ritonavir, Tenofovir, Viral Load
Abstract

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 log(10) 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.

DOI10.1093/infdis/jir188
Alternate JournalJ. Infect. Dis.
PubMed ID21606537
PubMed Central IDPMC3100514
Grant ListAI069501 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 RR024992 / RR / NCRR NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States