Researchers are tacking on bone deterioration to the list of hazards associated with potent AIDS medications. However, they consider it a small trade-off for the dramatic cut in death rates among AIDS patients taking these drugs.
Reporting in the March 10, 2000, issue of AIDS, Pablo Tebas, M.D., assistant professor of medicine in the infectious diseases division at Washington University School of Medicine in St. Louis, says that protease inhibitors appear to leach minerals from the bones of some HIV patients.
In a study of HIV-infected men who underwent bone scans, Tebas found that the probability that patients on highly active antiretroviral therapy (HAART) involving protease inhibitors would have a condition called osteopenia was double that for patients who were not taking the inhibitors. Both osteopenia and osteoporosis weaken bones by reducing bone mass and increasing the risk of subsequent fractures. Osteopenia leaches minerals from bones, whereas osteoporosis makes bones porous. Osteoporosis is a more severe form of osteopenia, with a higher risk of fracture.
The study does not prove causation, but it does demonstrate an association between osteopenia and protease inhibitors. "We don't know if this effect results from the protease inhibitors alone or from the combination of protease inhibitors and other commonly used drugs called nucleoside analogs," he said. "That is something that must be studied prospectively, which is what we're doing now."
This research was conducted at the AIDS Clinical Trials Unit at the School of Medicine and supported by the National Institutes of Health.
Scans detect trouble
Initially, Tebas and his team were investigating fat redistribution in patients who were on HAART. More than 50 percent of patients using protease inhibitors experience this metabolic problem, in which fat relocates from the limbs and the face and settles in the abdomen. In an effort to understand this change, Tebas used dual-energy X-ray absorptiometry to evaluate the amount of muscle and fat subjects had in their arms, legs and abdomen. Because the scan also indicates bone mass, the researchers began to observe that many of these patients had low bone-mineral density.
Taking the data from the fat-redistribution studies, Tebas divided the 112 male subjects into three groups: 60 HIV patients on HAART, 35 HIV patients on other therapies or no therapy and 17 HIV-negative subjects to serve as controls.
Using World Health Organization (WHO) guidelines, he determined that half of the patients taking protease inhibitors met the WHO definition for osteopenia. Twenty percent of the subjects taking HAART had severe bone loss compared with only 6 percent of the control group.
"We also looked at whether there is a relationship between fat redistribution and osteopenia, but we found no association," Tebas said.
Continue medications
Tebas urges patients using protease inhibitors to continue taking them. "While osteopenia appears to be a side effect of the therapy, these medicines have other beneficial effects," he said. "They have turned HIV infection into a chronic disease that we can manage on an outpatient basis, and have dramatically reduced the mortality of AIDS."
He points out that the FDA approved the drugs very quickly and without long-term safety data because of the large numbers of people dying of AIDS. "We are starting to see the long-term side effects of therapy and the price that we pay for using these medicines, which includes fat redistribution, high lipid levels and osteopenia," he said. "What we need to do now is find out why these things happen and then try to prevent them."
Note: For more information, refer to Tebas P, Powderly WG, Claxton S, Marin D, Tantisiriwat W, Teitelbaum, Yarasheski KE, "Accelerated Bone Mineral Loss in HIV-Infected Patients Receiving Potent Antiretroviral Therapy," AIDS, vol.14(4) pp. 63-67, March 10, 2000.
Journal
AIDS