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Role Of Antiretrovirals In Bone Fractures In People With HIV Remains Unclear (IAS 2011)

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Published: Jul 29, 2011 1:07 pm
Role Of Antiretrovirals In Bone Fractures In People With HIV Remains Unclear (IAS 2011)

Results from a recent large study indicate that the role of antiretrovirals in the risk of bone fractures in people with HIV remains unclear. The researchers found that use of Viread and Kaletra were associated with a higher risk of bone fractures in the era of combination antiretroviral therapy; however, they also found that traditional risk factors, such as older age and low body weight, were more important in determining fracture risk.

“Cumulative antiretroviral therapy exposure risk is modest compared to the traditional risk factors for osteoporosis,” said Dr. Roger Bedimo from the Veterans Affairs North Texas Health Care System, who presented the results last week at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2011).

“A significant increase in the fracture rate was noted in the HAART [highly active antiretroviral therapy] era, but we cannot infer that this is due to antiretroviral exposure per se,” he added. Dr. Bedimo noted that the increase could be due to longer survival times, for example, rather than a direct effect of the antiretrovirals on bone loss.

Traditional risk factors for bone fractures include older age, low weight or body mass index, smoking, excessive alcohol consumption, and corticosteroid use. Corticosteroids are drugs used to treat conditions such as asthma and arthritis.

Previous studies have shown that low bone density and bone fractures are more common in people with HIV than in uninfected individuals (see related AIDS Beacon news).

Additional risk factors for bone fractures in people with HIV may include hepatitis B and C infections and proton pump inhibitor use. Proton pump inhibitors are drugs used to reduce acid levels in the stomach; common drugs in this class include omeprazole (Prilosec), lansoprazole (Prevacid), and Nexium (esomeprazole).

Previous studies have also indicated that certain antiretroviral drugs may be associated with low bone density in people with HIV. In particular, use of the nucleoside reverse transcriptase inhibitor Viread (tenofovir) and boosted protease inhibitors have been linked to low bone density. Viread is also a component of Truvada (emtricitabine/tenofovir) and Atripla (efavirenz/emtricitabine/tenofovir).

However, it is not clear if these antiretrovirals are associated directly with an increased risk for bone fractures or just low bone density.

In this study, researchers investigated whether the use of antiretrovirals over time is associated with increased bone fractures. The study included 56,660 HIV-positive adults who received care through the Veterans Health Administration between 1984 and 2009.

More than 98 percent of the study participants were men, with an average age of 45 years old. Participants were followed for a median of 4.5 years.

The authors assessed how many participants reported wrist, back, or hip fractures during this time. According to the researchers, these types of fractures are most likely to occur due to osteoporosis, or low bone density.

Results showed that 951 patients sustained at least one fracture. In particular, 124 patients sustained back fractures, 486 patients sustained wrist fractures, and 341 patients sustained hip fractures.

Results also showed that the rate of fractures increased over time. Participants in the HAART era (1996 to 2009) reported bone fractures at a rate that was 2.5 times higher than participants in the pre-HAART era.

Further analysis showed that use of Viread or Kaletra (lopinavir/ritonavir) was associated with a 13 percent increased risk of bone fractures in the HAART era, after taking into account age, race, and other risk factors.

The researchers found no link between the risk of bone fracture and the use of Ziagen (abacavir), zidovudine (Retrovir), stavudine (Zerit), non-nucleoside reverse transcriptase inhibitors, or other protease inhibitors (boosted or unboosted).

However, the researchers noted that traditional risk factors were more highly associated with an increased risk of bone fractures. Caucasian race increased the risk by 61 percent, smoking by 49 percent, older age by 48 percent, and low body mass index by 48 percent.

Dr. Bedimo also stated that cumulative antiretroviral exposure is likely not directly linked to a higher bone fracture risk in the HAART era. Instead, he suggested that the effects could be due to patients living longer or the fact that fewer participants were taking sub-optimal treatment regimens or no antiretrovirals at all and thus would have a higher risk of going on to develop long-term complications such as bone fractures.

For more information, please see the study abstract and presentation on the IAS 2011 conference website.

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