Dominique Costagliola1, Valérie Potard1,2, Sylvie Lang1,2,3, Sophie Abgrall1,4, Claudine Duvivier5, Hugues Fischer6, Véronique Joly7, Jean-Marc Lacombe1,2, Marc-Antoine Valantin1,8, Murielle Mary-Krause1, Sylvie Rozenberg8. 1. INSERM, Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France. 2. Inserm Transfert, Paris, France. 3. Service de Cardiologie, APHP, Hôpital Saint-Antoine, Hôpitaux de l'Est Parisien, Sorbonne Université, Paris, France. 4. Service de Médecine Interne et Immunologie Clinique, APHP, Hopital Antoine Béclère, Clamart, France. 5. Service de Maladies Infectieuses et Tropicales, Centre d'infectiologie Necker-Pasteur, APHP, Hôpital Necker-Enfants Malades, IHU Imagine, Paris, France. 6. TRT5, Paris, France. 7. Service de Maladies Infectieuses et Tropicales, APHP, Hopital Bichat, Paris, France. 8. Service de Maladies Infectieuses et Tropicales, APHP, Hôpital Pitié-Salpêtrière, Paris, France.
Abstract
BACKGROUND: HIV-infected patients have lower bone mineral density and a higher incidence of fractures than the general population of the same age and sex. To assess the impact of antiretroviral (ARV) drugs exposure on the risk of osteoporotic fractures, we conducted a nested case-control study. METHODS: Cases were individuals enrolled while ARV-naive, with a first prospectively recorded fracture between 2000 and 2010. Controls were randomly selected after matching for sex, age (±3 years), period of HIV diagnosis (<1997/≥1997), and clinical center. The risk of fracture was analyzed with conditional logistic regression models, using different ways to model ARV exposure. All exposure variables and potential confounders were included in multivariable models. RESULTS: Among 861 reviewed cases, 261 fractures were osteoporotic and 254 of cases were matched to at least one control (376 controls). The median year of fracture diagnosis was 2007 (interquartile range 2004-2009): 49% of patients had been exposed to tenofovir disoproxil fumarate (TDF) and 82% to protease inhibitors (PIs). After taking into account the transmission group, AIDS status, geographic origin, body mass index, current smoking status, alcohol consumption, exposure to systemic glucocorticoids, and the period of enrollment, there was no association between the risk of fracture and exposure to TDF [odds ratio for cumulative exposure: 1.04 (0.86-1.27), similar results for ever-exposed subjects], to nucleoside reverse transcriptase inhibitors, or to PIs [odds ratio for cumulative PI exposure: 1.02 (0.92-1.12)]. CONCLUSIONS: We found no evidence of an excess risk of fracture after exposure to TDF or PIs. This has important implications for the debate concerning tenofovir alafenamide versus generic TDF.
BACKGROUND:HIV-infectedpatients have lower bone mineral density and a higher incidence of fractures than the general population of the same age and sex. To assess the impact of antiretroviral (ARV) drugs exposure on the risk of osteoporotic fractures, we conducted a nested case-control study. METHODS: Cases were individuals enrolled while ARV-naive, with a first prospectively recorded fracture between 2000 and 2010. Controls were randomly selected after matching for sex, age (±3 years), period of HIV diagnosis (<1997/≥1997), and clinical center. The risk of fracture was analyzed with conditional logistic regression models, using different ways to model ARV exposure. All exposure variables and potential confounders were included in multivariable models. RESULTS: Among 861 reviewed cases, 261 fractures were osteoporotic and 254 of cases were matched to at least one control (376 controls). The median year of fracture diagnosis was 2007 (interquartile range 2004-2009): 49% of patients had been exposed to tenofovir disoproxil fumarate (TDF) and 82% to protease inhibitors (PIs). After taking into account the transmission group, AIDS status, geographic origin, body mass index, current smoking status, alcohol consumption, exposure to systemic glucocorticoids, and the period of enrollment, there was no association between the risk of fracture and exposure to TDF [odds ratio for cumulative exposure: 1.04 (0.86-1.27), similar results for ever-exposed subjects], to nucleoside reverse transcriptase inhibitors, or to PIs [odds ratio for cumulative PI exposure: 1.02 (0.92-1.12)]. CONCLUSIONS: We found no evidence of an excess risk of fracture after exposure to TDF or PIs. This has important implications for the debate concerning tenofovir alafenamide versus generic TDF.
Authors: Matthew A Spinelli; David V Glidden; Peter L Anderson; Monica Gandhi; Vanessa M McMahan; Patricia Defechereux; Mauro Schechter; Valdiléa G Veloso; Suwat Chariyalertsak; Juan V Guanira; Linda-Gail Bekker; Susan P Buchbinder; Robert M Grant Journal: AIDS Res Hum Retroviruses Date: 2019-06-19 Impact factor: 2.205
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