Álvaro H Borges1,2, Jennifer Hoy3, Eric Florence4, Dalibor Sedlacek5, Hans-Jürgen Stellbrink6, Vilma Uzdaviniene7, Janez Tomazic8, Panagiotis Gargalianos-Kakolyris9, Patrick Schmid10, Chloe Orkin11, Court Pedersen12, Clifford Leen13, Christian Pradier14, Fiona Mulcahy15, Anna Lisa Ridolfo16, Therese Staub17, Fernando Maltez18, Rainer Weber19, Leo Flamholc20, Galina Kyselyova21, Jens D Lundgren1, Amanda Mocroft22. 1. Centre of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, and. 2. Institute for Clinical Medicine, University of Copenhagen, Denmark. 3. Department of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, Australia. 4. Institute of Tropical Medicine, Antwerp, Belgium. 5. Charles University Hospital Plzen, Czech Republic. 6. Infektionsmedizinisches Centrum Hamburg (ICH) Study Center, Innere Medizin, Hamburg, Germany. 7. Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. 8. University Medical Centre Ljubljana, Clinic of Infectious Diseases Ljubljana, Medical Faculty, University of Ljubljana, Slovenia. 9. The General Hospital of Athens "G. Gennimatas" First Department Of Medicine - Infectious Diseases Unit, Athens, Greece. 10. Division of Infectious Diseases, Cantonal Hospital St. Gallen, Switzerland. 11. Barts and The Royal London Hospital NHS Trust, London, United Kingdom. 12. Odense Universitetshospital, Forskningsenheden, Denmark. 13. Western General Hospital, Edinburgh, United Kingdom. 14. CHU Nice Hopital de l' Archet 1, Nice, France. 15. St. James' Hospital, Dublin, Ireland. 16. Ospedale L. Sacco, Milan, Italy. 17. Centre Hospitalier de Luxembourg, Luxemborg. 18. Hospital Curry Cabral, Lisbon, Portugal. 19. University Hospital Zürich, Switzerland. 20. Skåne University Hospital, Malmö, Sweden. 21. Crimean Republican AIDS Centre, Simferopol, Ukraine; and. 22. Department of Infection and Population Health, University College London, UK.
Abstract
BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.
BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.
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