Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort
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Publication Date: | 2017 |
Other Authors: | , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | http://hdl.handle.net/10400.17/3861 |
Summary: | 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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Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV CohortHCC INFAdultFemaleMaleHumansAnti-HIV Agents / administration & dosageMiddle AgedAnti-HIV Agents / adverse effectsAnti-HIV Agents / therapeutic useBone Density / drug effectsCD4 Lymphocyte CountCohort StudiesCoinfection / epidemiologyData CollectionEurope / epidemiologyFemoral Fractures / epidemiologyFemoral Fractures / etiologyFemoral Fractures / virologyFractures, Bone / epidemiologyFractures, Bone / ethnologyFractures, Bone / etiologyFractures, Bone / virologyHIV Infections / complicationsHIV Infections / drug therapyHIV Infections / epidemiologyHIV Infections / virologyOsteonecrosis / epidemiologyOsteonecrosis / etiologyOsteonecrosis / virologyRegression AnalysisRisk FactorsTenofovir / adverse effectsTenofovir / therapeutic useBackground: 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.OxfordRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEBorges, AHoy, JFlorence, ESedlacek, DStellbrink, HJUzdaviniene, VTomazic, JGargalianos-Kakolyris, PSchmid, POrkin, CPedersen, CLeen, CPradier, CMulcahy, FRidolfo, AStaub, TMaltez, FWeber, RFlamholc, LKyselyova, GLungren, JMocroft, AEuroSIDA2021-10-04T11:41:22Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/3861engClin Infect Dis. 2017 May 15;64(10):1413-1421.10.1093/cid/cix167.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-10T09:44:28Zoai:repositorio.chlc.min-saude.pt:10400.17/3861Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:21:10.587186Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort |
title |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort |
spellingShingle |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort Borges, A HCC INF Adult Female Male Humans Anti-HIV Agents / administration & dosage Middle Aged Anti-HIV Agents / adverse effects Anti-HIV Agents / therapeutic use Bone Density / drug effects CD4 Lymphocyte Count Cohort Studies Coinfection / epidemiology Data Collection Europe / epidemiology Femoral Fractures / epidemiology Femoral Fractures / etiology Femoral Fractures / virology Fractures, Bone / epidemiology Fractures, Bone / ethnology Fractures, Bone / etiology Fractures, Bone / virology HIV Infections / complications HIV Infections / drug therapy HIV Infections / epidemiology HIV Infections / virology Osteonecrosis / epidemiology Osteonecrosis / etiology Osteonecrosis / virology Regression Analysis Risk Factors Tenofovir / adverse effects Tenofovir / therapeutic use |
title_short |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort |
title_full |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort |
title_fullStr |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort |
title_full_unstemmed |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort |
title_sort |
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort |
author |
Borges, A |
author_facet |
Borges, A Hoy, J Florence, E Sedlacek, D Stellbrink, HJ Uzdaviniene, V Tomazic, J Gargalianos-Kakolyris, P Schmid, P Orkin, C Pedersen, C Leen, C Pradier, C Mulcahy, F Ridolfo, A Staub, T Maltez, F Weber, R Flamholc, L Kyselyova, G Lungren, J Mocroft, A EuroSIDA |
author_role |
author |
author2 |
Hoy, J Florence, E Sedlacek, D Stellbrink, HJ Uzdaviniene, V Tomazic, J Gargalianos-Kakolyris, P Schmid, P Orkin, C Pedersen, C Leen, C Pradier, C Mulcahy, F Ridolfo, A Staub, T Maltez, F Weber, R Flamholc, L Kyselyova, G Lungren, J Mocroft, A EuroSIDA |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Borges, A Hoy, J Florence, E Sedlacek, D Stellbrink, HJ Uzdaviniene, V Tomazic, J Gargalianos-Kakolyris, P Schmid, P Orkin, C Pedersen, C Leen, C Pradier, C Mulcahy, F Ridolfo, A Staub, T Maltez, F Weber, R Flamholc, L Kyselyova, G Lungren, J Mocroft, A EuroSIDA |
dc.subject.por.fl_str_mv |
HCC INF Adult Female Male Humans Anti-HIV Agents / administration & dosage Middle Aged Anti-HIV Agents / adverse effects Anti-HIV Agents / therapeutic use Bone Density / drug effects CD4 Lymphocyte Count Cohort Studies Coinfection / epidemiology Data Collection Europe / epidemiology Femoral Fractures / epidemiology Femoral Fractures / etiology Femoral Fractures / virology Fractures, Bone / epidemiology Fractures, Bone / ethnology Fractures, Bone / etiology Fractures, Bone / virology HIV Infections / complications HIV Infections / drug therapy HIV Infections / epidemiology HIV Infections / virology Osteonecrosis / epidemiology Osteonecrosis / etiology Osteonecrosis / virology Regression Analysis Risk Factors Tenofovir / adverse effects Tenofovir / therapeutic use |
topic |
HCC INF Adult Female Male Humans Anti-HIV Agents / administration & dosage Middle Aged Anti-HIV Agents / adverse effects Anti-HIV Agents / therapeutic use Bone Density / drug effects CD4 Lymphocyte Count Cohort Studies Coinfection / epidemiology Data Collection Europe / epidemiology Femoral Fractures / epidemiology Femoral Fractures / etiology Femoral Fractures / virology Fractures, Bone / epidemiology Fractures, Bone / ethnology Fractures, Bone / etiology Fractures, Bone / virology HIV Infections / complications HIV Infections / drug therapy HIV Infections / epidemiology HIV Infections / virology Osteonecrosis / epidemiology Osteonecrosis / etiology Osteonecrosis / virology Regression Analysis Risk Factors Tenofovir / adverse effects Tenofovir / therapeutic use |
description |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z 2021-10-04T11:41:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.17/3861 |
url |
http://hdl.handle.net/10400.17/3861 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Clin Infect Dis. 2017 May 15;64(10):1413-1421. 10.1093/cid/cix167. |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Oxford |
publisher.none.fl_str_mv |
Oxford |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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