No link between antiretroviral treatment and fracture risk
Antiretroviral therapy, and in particular tenofovir, is not associated with an excess risk of bone fracture, in contrast to what has often been suggested. This is what Dominique Costagliola and colleagues (Institut Pierre Louis d’épidémiologie et de santé publique Inserm, UPMC, FHDH ANRS CO4 cohort) have shown in an ANRS- and ANSM-supported study conducted with a member of the nonprofit organization Act Up-Paris. The findings will be presented in an oral communication on 26 July 2017 during the 9th Conference on HIV Science (IAS 2017), organized by the International AIDS Society and the ANRS in Paris from July 23rd to 26th 2017.
HIV-infected people have a lower bone mineral density (BMD) than members of the general population and a higher risk of bone fracture. Several studies have suggested a link between this decrease in BMD and treatment with antiretroviral drugs, particularly the nucleotide reverse transcriptase inhibitor tenofovir, and with protease inhibitors. The effect of antiretrovirals on fracture risk is nonetheless contentious. "Among the seven published studies, only one reports an increased fracture risk with tenofovir. The others do not necessarily find a link with tenofovir or protease inhibitors. Not to mention that the full treatment history of the patients is not always taken into account," emphasizes Dominique Costagliola (Institut Pierre Louis d’épidémiologie et de santé publique Inserm, UPMC), who runs the study the results of which will be presented in an oral communication on 26 July, during IAS 2017, which was organized by the IAS and the ANRS (23-26 July, Paris).
Dominique Costagliola and her colleagues have conducted an ANRS- and ANSM-supported case-control study of the effect of antiretroviral drugs on fracture risk, in FHDH ANRS CO4, a French cohort of people living with HIV and treated in hospital that was set up in 1989. Focusing on osteoporotic fracture sites (vertebrae, hip, wrist,…), the re-searchers just considered low-energy fractures (occurring after low-energy trauma), and included all risk factors for bone loss, like age, body mass index (BMI), smoking, alcohol consumption, and corticosteroid treatment.
Of 861 patients who had not started antiretroviral therapy at the time of their inclusion in the cohort and who suffered a fracture between 2000 and 2010, 261 had a low-energy fracture at an osteoporotic site. The patients had a mean age of 49 years and were mostly exposed to tenofovir (49 % of patients) and protease inhibitors (82 %). The data collected were compared with data from patients with a similar profile, notably age, sex, and time of diagnosis of HIV infection, but who did not report a fracture over the same period. The analysis showed there was no association between the risk of fracture, the type of antiretroviral therapy (protease inhibitor or tenofovir), or the duration of exposure to treatment. "On the other hand", notes Dominique Costagliola, "we found an increased fracture risk with the usual factors, like low BMI, alcohol consumption, or use of glucocorticoids."
"A decrease in BMD was observed with tenofovir, but only in the first year," notes Dominique Costagliola. "In the longer term, bone loss was similar in HIV-infected patients and patients not infected. These data on tenofovir are particularly important as the question now relates to the value of treatment with next-generation tenofovir, tenofovir alafenamide fumarate, which is believed to have less impact on bone, compared with tenofovir generics. Tenofovir alafenamide fumarate is currently proposed as an alternative, while tenofovir generics should soon be on the market."
Professor François Dabis, director of the ANRS, considers that "These results, recorded in a large number of patients, are encouraging for patients who have been on antiretrovirals for several years and who are wondering about side effects. They should also be considered in light of the fact that the generic form of tenofovir should soon become available."
Impact of exposure to each antiretroviral treatment (ARV) on the risk of fracture in HIV-1 infected individuals, an analysis from FHDH ANRS CO4.
D. Costagliola1, V. Potard1,2, S. Lang1,2, S. Abgrall1,3, C. Duvivier4,5, H. Fischer6, V. Joly7, J.-M. Lacombe1,2, M.-A. Valantin1,8, M. Mary- Krause1, S. Rozenberg9, on behalf of the FHDH ANRS CO4.
1Sorbonne Universités, INSERM, UPMC Univ Paris 06, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS1136), Paris, France, 2INSERM Transfert, Paris, France, 3AP-HP, Hôpital Antoine Béclère, Service de Médecine interne/Immunologie clinique, Clamart, France, 4AP-HP, Hôpital Necker-Enfants Malades, Service des maladies infectieuses et tropicales, Paris, France, 5Institut Pasteur, Centre Médical de l'Institut Pasteur, Paris, France, 6ACT-UP Paris, Paris, France, 7AP-HP, Hôpital Bichat, Service de maladies infectieuses et tropicales, Paris, France, 8AP-HP, Hôpital Pitié-Salpêtrière, Service de maladies infectieuses et tropicales, Paris, France, 9AP-HP, Hôpital Pitié-Salpêtrière, Service de rhumatologie, Paris, France.