2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13-15 September 2000, Toronto, Canada

LONGITUDINAL ANALYSIS OF BONE MINERAL DENSITY (BMD) IN HIV-INFECTED PATIENTS TREATED WITH HAART: CHANGES IN BMD CORRELATE WITH CHANGE IN SUBCUTANEOUS FAT; WITH AN ADDITIONAL INDEPENDENT EFFECT OF INDINAVIR THERAPY TO INCREASE BMD

Antiviral Therapy 2000; 5(Suppl. 5):20 (abstract no. O31)

D Nolan, R Upton, I James, E McKinnon, M John and S Mallal
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University,Western Australia

INTRODUCTION: Recent cross-sectional studies of BMD in HIV-infected patients on HAART suggested that PI therapy is associated with reduced BMD, raising concerns that long-term PI use may lead to premature osteoporosis. We sought to determine the predictors of change in BMD over time in a large cohort of HIV-infected patients on HAART.

METHODS: (1) Cross-sectional analysis - whole body DEXA scans (Hologic system) were conducted in 171 male participants in the WA HIV cohort, and lumbar spine Z-scores in the most recent scan on therapy were compared. (2) Longitudinal analysis - rates of loss of BMD in serial DEXA scans from patients on a stable therapeutic regimen (n=64) were also compared in a multivariate analysis, taking into account multiple potentially predictive factors.

RESULTS: Cross-sectional analysis revealed relatively high rates of osteopenia (49%) and osteoporosis (17%) and relatively lower bone mineral density in patients receiving PIs (mean Z-score±SD, -0.77±1.16) compared to PI-naïve (-0.358±1.18; P=0.055), as previously described. Longitudinal analysis revealed a positive correlation between rate of change in subcutaneous fat (mean change %leg fat/year) and change in BMD (change in lumbar spine Z-score/year) (P=0.008). Patients receiving indinavir therapy had greater increases in BMD (mean increase Zscore/ year±SE adjusted for Δ%leg fat, 0.407±0.115) than nelfinavir regimens (0.145±0.136), independent of changes in subcutaneous fat (P=0.0369, multivariate analysis).

CONCLUSIONS: Changes in BMD in a longitudinal analysis are positively correlated with changes in %subcutaneous fat, regardless of therapy. In addition, indinavir use is independently associated with increased BMD gain, in keeping with in vitro experimental data indicating that indinavir favours osteogenic differentiation of mesenchymal stem cells via retinoid signalling mechanisms.

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O31

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