10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 6-8 November 2008, London, UK

CONTINUOUS ANTIRETROVIRAL THERAPY DECREASES BONE MINERAL DENSITY: RESULTS FROM THE SMART STUDY

Antiviral Therapy 2008; 13(Suppl. 4):A14 (abstract no. O-19)

B Grund¹, G Peng¹, R Isaksson¹, K Ellis², C Gibert³, J Shlay⁴, F Drummond⁵, E Martinez⁶, J Hoy⁷, P Reiss⁸, W El-Sadr⁹, A Thomas¹, F Visnegarwala¹⁰, A Carr¹¹ and the Body Composition Sub-study Investigators of the Strategies for Management of Anti-Retroviral Therapy (SMART) Study
¹University of Minnesota, Minneapolis, MN, USA; ²Baylor College of Medicine, Houston, TX, USA; ³Veterans Affairs Medical Center, Washington, DC, USA; ⁴University of Colorado Health Sciences Center, Denver, CO, USA; ⁵National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; ⁶Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; ⁷Alfred Hospital and Monash University, Melbourne, Australia; ⁸National AIDS Therapy Evaluation Center, Academic Medical Center, Amsterdam, the Netherlands; ⁹Harlem Hospital and Columbia University, New York, NY, USA; ¹⁰AbsoluteCare Medical Center, Atlanta, GA, USA, ¹¹St Vincent’s Hospital and University of New South Wales, Sydney, Australia

BACKGROUND: HIV-infected adults have lower bone mineral density (BMD) than the general population and might experience more fractures. We evaluated the role of antiretroviral therapy (ART) on BMD and fracture risk.

METHODS: In the SMART trial, HIV-positive patients with CD4 counts >350 cells/mm³ were randomly allocated to continuous ART (viral suppression [VS] group) or CD4 guided intermittent ART (drug conservation [DC] group). In 214 participants, hip and spine BMD were measured annually by dual-energy X-ray absorptiometry (DEXA) and trabecular BMD of the spine by quantitative computed tomography (qCT). We compared treatment groups for change in BMD using longitudinal models and, in the full SMART study (n=5,472), for incidence of fractures using Cox regression. In the VS cohort, we prospectively evaluated associations of BMD decline with cumulative ART use and other factors.

RESULTS: Participants (median 44 years; 19% female; 73% on ART; 12% with osteoporosis; median T-scores -0.5 [femur], -0.9 [spine qCT], and -0.7 [spine DXA]; 98 randomized to the VS group and 116 to the DC group) were followed for a mean of 2.4 years. In the VS group, participants received ART for 93% of follow-up time, compared with 37% in the DC group. BMD declined by 0.9% per year (femur), 2.9% (spine qCT) and 0.4% (spine DXA) in the VS group, and significantly less in the DC group. Estimated DC versus VS group differences in mean BMD change from baseline through follow-up were 1.4% (95% confidence interval [CI] 0.5–2.3, P=0.002) at the femur, 2.9% (95% CI 0.7–5.1, P=0.01) for spine by qCT and 1.2% (95% CI 0.02–2.3, P=0.05) for spine by DEXA. No consistent drug-specific association with BMD decline was found. In the parent study, 10 of 2,753 participants in the VS group (0.13 per 100 person-years of follow-up) and 2 of 2,720 participants in the DC group (0.03 per 100 person-years of follow-up) reported fractures as grade 4 adverse events (hazard ratio 4.9 [95% CI 1.1–22.5], P=0.04).

CONCLUSIONS: Continuous ART is associated with progressive decline in BMD and possibly more fractures relative to intermittent, CD4-guided ART.

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2008-11-06
O-19

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