Cautious use of TDF among those at fracture risk recommended

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Viread, in contrast with other antiretroviral medications, was associated with an increased risk for bone fractures in people with HIV in a recent study. Healio reports that patients who had used or were currently using Viread (tenofovir disoproxil fumarate, Gilead Sciences; TDF) had significantly more fractures. An association with cumulative use of the drug, however, was insignificant in the study.

“Our study supports cautious use of TDF among HIV–positive persons at fracture risk initiating ART as recommended by current guidelines and expert panels,” study researchers led by Álvaro H Borges at the Centre of Excellence for Health, Immunity and Infections (CHIP), department of infectious diseases, section 2100, Rigshospitalet, University of Copenhagen and the Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, wrote. They added that other factors increase the risk for fractures and osteonecrosis, or bone tissue death.

“Host factors, HIV–specific variables and comorbidities contribute to the risk of these bone events,” they explained.

The study involved 11,820 patients with HIV. They were among the more than 20,000 enrolled in the EuroSIDA study – a long-term follow-up of such patients undergoing care in 35 European countries, Israel and Argentina. Of those involved in the study, 496 patients suffered 619 fractures. Seventy-three patients developed 89 cases of osteonecrosis of the femoral head, which is the top portion of the femur.

The researchers compared the incidence of bone events for patients on TDF with that of patients using any of five other antiretrovirals – Videx (didanosine, Bristol-Myers Squibb), Crixivan (indinavir, Merck), Invirase (saquinavir, Hoffmann La Roche), Norvir (ritonavir, Hoffmann La Roche), Norvir (ritonavir, AbbVie) and Kaletra (lopinavir/ritonavir, AbbVie).

Patients who had ever used TDF (adjusted incidence rate ratio [aIRR] = 1.4/1,000 person years of follow-up [PYFU]), along with those who were using it at the time of the study (aIRR = 1.25/1,000 PYFU), “had a significantly increased incidence of fractures,” the researchers reported.

There was no difference in the risk for fractures in those using TDF without a boosted protease inhibitor or those using a boosted protease inhibitor without TDF compared with those using both.

Meanwhile, TDF and the other five antiretrovirals included in the study – for those patients who had ever used them – were all associated with a non-significant increased risk for osteonecrosis of the femoral head.

Because TDF, indinavir and saquinavir are not often used anymore, researchers did not have enough data on the risk of current use for fractures.

The researchers found no association between cumulative exposure to any of the drugs and osteonecrosis.

The study also included associations between fracture risk and factors like age, race, IV drug use, HCV coinfection and others.

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/1000PYFU 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 (1.08/5y exposure; 0.94-1.25). No other ARV was associated with fractures (all p>0.1). 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 HIV infection, host factors, HIV-specific variables and co-morbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

Álvaro H Borges, Jennifer Hoy, Eric Florence, Dalibor Sedlacek, Hans-Jürgen Stellbrink, Vilma Uzdaviniene, Janez Tomazic, Panagiotis Gargalianos-Kakolyris, Patrick Schmid, Chloe Orkin, Court Pedersen, Clifford Leen, Christian Pradier, Fiona Mulcahy, Anna Lisa Ridolfo, Therese Staub, Fernando Maltez, Rainer Weber, Leo Flamholc, Galina Kyselyova, Jens D Lungren, Amanda Mocroft

Healio report
Clinical Infectious Diseases abstract

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