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.
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%; tenofovir-emtricitabine group, -2.4%; P = .036). BMD loss of >or=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 >or=6% in the hip; 15% vs 5% had a loss of >or=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; tenofovir-emtricitabine 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.
Stellbrink
Hans-Jürgen
HJ
Infektions Medizinisches Centrum Hamburg Study Center, Hamburg, Germany.
Orkin
Chloe
C
Arribas
Jose Ramon
JR
Compston
Juliet
J
Gerstoft
Jan
J
Van Wijngaerden
Eric
E
Lazzarin
Adriano
A
Rizzardini
Giuliano
G
Sprenger
Herman G
HG
Lambert
John
J
Sture
Gunta
G
Leather
David
D
Hughes
Sara
S
Zucchi
Patrizia
P
Pearce
Helen
H
D015502:Absorptiometry, Photon; D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D004338:Drug Combinations; D000068679:Emtricitabine; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D000068698:Tenofovir; D055815:Young Adult; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir