Protease inhibitors linked to bone disease in HIV/AIDS patients

June 15, 2000

HOT SPRINGS, Va. -- Chronic use of protease inhibitors is associated with an increased risk of bone disease in HIV/AIDS patients, according to a new UC Francisco study.

Research results showed a link between patients undergoing treatment with this class of drugs and development of tissue death in the top end of the thighbone that forms the ball of the hip joint. Known as avascular necrosis (AVN) of the femoral head, the first symptom of the bone disorder is pain in the groin and hip area when bearing body weight.

"Protease inhibitors have greatly improved the survival of HIV-infected patients and they have an important role in treating HIV disease, but our study results indicate that clinicians need to show higher vigilance for AVN in HIV patients who are on this drug regimen," said study director Guy Paiement, MD, UCSF associate professor of orthopedic surgery.

With early diagnosis, he emphasized, AVN can be treated effectively. Paiement presented the research findings here today (Friday, June 16) at the annual meeting of the American Orthopedic Association.

Protease inhibitors were introduced as an HIV treatment regimen in the mid-1990s, and since then, Paiement said he has observed an increasing number of AVN cases in the HIV population at San Francisco General Hospital Medical Center, where he serves as chief of orthopedic surgery.

The study evaluated 18 HIV patients at SFGHMC who were diagnosed with AVN between 1991-99. Eleven were using protease inhibitors prior to developing AVN, and in this group, ten had no other risk factors for the bone disease. Among the seven patients not taking protease inhibitors, only one had no risk factor. Risk factors for AVN include steroid use and alcohol consumption. "The difference in these two patient groups is statistically significant and supports the evidence reported from other researchers that AVN in this particular population may be directly related to protease inhibitor use," Paiement said.

Patients in the study group ranged in age from 26 to 54 years and their use of protease inhibitors ranged from six to 36 months. Their protease regimens included indinavir, nelfinavir, ritonavir, and saquinavir, singly or in various combinations.

Protease inhibitors work by halting the action of the protease enzyme, a protein produced by HIV that is necessary for replication of the virus. One of the common side-effects of these drugs is a disruption in the body's normal process of fat metabolism, resulting in increased levels of fat in the circulatory system.

This appears to set the stage for AVN, according to Paiement, because the extra fat molecules block the amount of blood that can feed into the bone tissue. Without an adequate blood supply, the bone begins to die.

If AVN is detected early, surgeons can treat it by drilling holes in the diseased bone tissue to allow for increased blood flow that helps prevent further deterioration. In the late stages of AVN of the femoral head, however, the only medical treatment is hip replacement surgery to implant an artificial joint, Paiement said, and this procedure is associated with a high risk of infection that presents a particular concern for HIV patients because of their compromised immune system status.
Study co-investigators are Ayaz A. Biviji, MD, UCSF resident in orthopedic surgery, and Andra Davidson, MEd, clinical research coordinator at SFGHMC. The research was supported by a grant from the SFGHMC Orthopedic Service.

NOTE TO THE MEDIA: To arrange an interview with Dr. Paiement, contact Corinna Kaarlela in the UCSF News Office at (415) 476-3804.

University of California - San Francisco

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