Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen.
BACKGROUND
Decreased bone mineral density (BMD) has been described in HIV-infected patients initiating antiretroviral therapy (ART), but the contributions of ART and immunologic and/or virologic factors remain unclear.


METHODS
We compared total BMD changes over 96 weeks in 106 ART-naive HIV-infected subjects who were randomized to receive efavirenz (EFV) + zidovudine/lamivudine (n = 32) or lopinavir/ritonavir (LPV/r) + zidovudine/lamivudine induction (n = 74) for 24-48 weeks followed by LPV/r monotherapy. We also sought to identify factors associated with BMD loss, including markers of systemic inflammation [soluble tumor necrosis factor-alpha receptors (sTNFR I and II)].


RESULTS
After 96 weeks, the mean percent change from baseline in total BMD was -2.5% (LPV/r) and -2.3% (EFV) (P < 0.01 for within-group changes in either arm; P = 0.86 for between-group differences). No alteration in the rate of BMD change was observed upon simplification to LPV/r monotherapy. Although soluble tumor necrosis factor-alpha receptor II concentrations at baseline and 24 weeks were at least marginally associated with subsequent changes in BMD (P = 0.06 and P = 0.028, respectively), these associations were no longer significant after adjustment for CD4 T cell count. Subjects with lower baseline CD4 T cell count, non-black race, and higher baseline glucose demonstrated a higher risk for >5% decrease in BMD.


CONCLUSIONS
Similar decreases in BMD over 96 weeks occurred in ART-naive subjects receiving either EFV-based regimen or LPV/r-based regimen, which was not altered by simplification to LPV/r monotherapy and was unrelated to markers of tumor necrosis factor-alpha activity.
Brown
Todd T
TT
Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, MD, USA.
McComsey
Grace A
GA
King
Martin S
MS
Qaqish
Roula B
RB
Bernstein
Barry M
BM
da Silva
Barbara A
BA
D015502:Absorptiometry, Photon; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects*; D048588:Benzoxazines / Q000009:adverse effects; D015519:Bone Density / Q000187:drug effects*; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D019259:Lamivudine / Q000009:adverse effects; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism; D011446:Prospective Studies; D011744:Pyrimidinones / Q000009:adverse effects; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012307:Risk Factors; D019438:Ritonavir / Q000009:adverse effects; D015215:Zidovudine / Q000009:adverse effects
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018836:Inflammation Mediators; D011744:Pyrimidinones; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; C098320:efavirenz; D019438:Ritonavir