Share this article on:

Loss of Bone Mineral Density After Antiretroviral Therapy Initiation, Independent of Antiretroviral Regimen

Brown, Todd T MD, PhD*; McComsey, Grace A MD; King, Martin S PhD; Qaqish, Roula B PharmD; Bernstein, Barry M MD; da Silva, Barbara A MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 2009 - Volume 51 - Issue 5 - p 554-561
doi: 10.1097/QAI.0b013e3181adce44
Clinical Science

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-α 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-α 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-α activity.

From the *Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, MD; †Department of Pediatrics, Rainbow Babies and Children's Hospital, Department of Pediatrics and Medicine, Case Western Reserve University, Cleveland, OH; and ‡Abbott, Abbott Park, IL.

Received for publication September 10, 2008; accepted February 27, 2009.

Funding Statement and Role of Funding Source: Abbott financially supported this clinical trial. Dr. T. T. Brown is supported by National Institutes of Health 5K23AT2862.

The data presented in our article have never been published in a peer-reviewed journal. The data from this article have been presented at a scientific conference in February 2008 in Boston, MA (T. T. Brown et al., 15th Conference on Retroviruses and Opportunistic Infections, poster presentation #966).

Drs. T. T. Brown and G. A. McComsey did not receive any financial compensation for their work on this project. Dr. T. T. Brown drafted the article in its entirety. The corresponding author had full access to all data and final responsibility for the decision to publish.

Study design and protocol were the responsibility of Abbott. Monitoring of sites was performed by Abbott and Covance, Inc (Princeton, NJ). Statistical analysis was performed by a qualified Abbott statistician. Interpretation of data, article preparation, and decision to publish were performed by Abbott in collaboration with clinical study collaborators serving as consultants.

The study is registered at http://clinicaltrials.gov, number NCT00075231.

Correspondence to: Barbara A. da Silva, MD, Abbott, 200 Abbott Park Rd, Department R48U, Bldg AP30-3, Abbott Park, IL 60064-6146 (e-mail: barbara.dasilva@abbott.com).

© 2009 Lippincott Williams & Wilkins, Inc.