ACTG 5224 -- Changes in Bones and Fat

Most large clinical trials have found that after starting highly active antiretroviral therapy (HAART) bone density decreases and then stabilizes. Researchers conducted a sub-study of the larger ACTG trial 5202 that focused on changes after two years in bones and limb fat when comparing different regimens. This sub-study was called ACTG 5224. For background information on ACTG 5202, please see the previous story.

In trial 5224, researchers analysed data collected from 269 participants whose average profile at the start of the study was as follows:

• 15% females, 85% males
• age: 38 years
• CD4+ count: 233 cells
• viral load: 42,000 copies/mL

Results -- Changes in the Spine and Hips

For the first six months of the study, the spines of participants became thinner. After this time they started to increase in density. The increase was greatest among users of Kivexa compared to Truvada, and this difference in improved bone density was statistically significant; that is, not likely due to chance alone. The hipbones of Truvada users became thinner.

Similarly, after the first six months, efavirenz users had increased bone density in their spine compared to atazanavir-ritonavir users. This difference was statistically significant. Neither efavirenz nor atazanavir-ritonavir had a significant effect on bone density in the hip.

Overall, about 4% of participants had a fracture. However, fracture rates were not different among the different study regimens.

Results -- Limb Fat

Some medicines used for the treatment of HIV infection can cause the fatty layer just under the skin (subcutaneous fat) to disappear. This can affect the appearance of the face and limbs. To assess changes in subcutaneous fat, studies use low-dose X-ray scans, called DEXA, of the limbs. Combinations that contained either Kivexa or Truvada had increased limb and trunk fat. Use of atazanavir-ritonavir resulted in a greater increase in limb fat than efavirenz

On average, about 16% of participants on each of the four study regimens lost at least 10% of subcutaneous fat in their limbs. Using this metric -- a 10% or greater loss of limb fat -- there were no statistically significant differences among study regimens.

Summary

• All regimens seemed to have been associated with accelerated bone loss at the onset, but bone density became stable after the first year.
• Truvada was linked to greater loss of bone density in the hip and spine than Kivexa. Use of atazanavir-ritonavir was linked to greater loss of bone density in the spine compared to efavirenz.
• Regimens containing either Kivexa or Truvada had increased limb and trunk fat.
• Use of atazanavir-ritonavir resulted in a greater increase in limb fat than efavirenz.
• Fat wasting occurred in about 16% of participants and did not differ by study regimen.

Reference

1. McComsey G, Kitch D, Darr E, et al. Bone and limb fat outcomes of ACTG 5224s, a substudy of ACTG A5202: a prospective, randomized, partially blinded phase III trial of abacavir/3TC or tenofovir/FTC with efavirenz or atazanavir/ritonavir for initial treatment of HIV-1 infection. In: Program and abstracts of the 17th Conference on Retroviruses and Opportunistic Infections, 16-19 February 2010, San Francisco, U.S. Abstract 106 LB.