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.

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.

• Authors: Grace A McComsey, Douglas Kitch, Eric S Daar, Camlin Tierney, Nasreen C Jahed, Pablo Tebas, Laurie Myers, Kathleen Melbourne, Belinda Ha, Paul E Sax
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 203 Issue 12 Pg. 1791-801 (Jun 15 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 21606537 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Anti-HIV Agents
• Benzoxazines
• Cyclopropanes
• Dideoxynucleosides
• Drug Combinations
• Oligopeptides
• Organophosphonates
• Pyridines
• abacavir, lamivudine drug combination
• Deoxycytidine
• Lamivudine
• Atazanavir Sulfate
• Tenofovir
• Emtricitabine
• Adenine
• efavirenz
• Ritonavir

Topics

• Absorptiometry, Photon
• Adenine (adverse effects, analogs & derivatives)
• Adult
• Alkynes
• Anti-HIV Agents (adverse effects)
• Antiretroviral Therapy, Highly Active (adverse effects)
• Atazanavir Sulfate
• Benzoxazines (adverse effects)
• Bone Density (drug effects)
• CD4 Lymphocyte Count
• Cyclopropanes
• Deoxycytidine (adverse effects, analogs & derivatives)
• Dideoxynucleosides (adverse effects)
• Drug Combinations
• Drug Therapy, Combination
• Emtricitabine
• Female
• Fractures, Bone (chemically induced, epidemiology)
• HIV Infections (complications, drug therapy)
• Humans
• Intention to Treat Analysis
• Lamivudine (adverse effects)
• Male
• Middle Aged
• Oligopeptides (adverse effects)
• Organophosphonates (adverse effects)
• Osteoporosis (chemically induced)
• Pyridines (adverse effects)
• Risk Factors
• Ritonavir (adverse effects)
• Tenofovir
• Viral Load