Policy Issues Related to New Metabolic Abnormalities in HIV Disease

Ronald Baker, PhD

The New Syndrome

There are increasing reports of an emerging new syndrome among people with HIV disease characterized by serious metabolic abnormalities. As reported in this issue of BETA, and elsewhere, physical symptoms include a loss of fat in the arms, legs, buttocks, and face (peripheral wasting), and an accumulation of fat in the abdomen ("protease paunch"), breasts, and back of the neck ("buffalo hump"). Other manifestations that may be associated with the syndrome include insulin resistance (sometimes with diabetes) and elevated blood lipid (fat) levels. The syndrome has been variously referred to as "peripheral lipodystrophy," "body fat redistribution," and "metabolic dysregulation."

Direction of Research

There is growing recognition of the need for more research on this new syndrome. Unfortunately, there is little agreement as to how to prioritize research or how to pay for it. The pharmaceutical industry is resisting any acknowledgement that the syndrome may be directly related to anti-HIV drug treatment. In fact, no one yet knows the exact cause of these metabolic abnormalities. However, the weight of the available evidence suggests a connection to anti-HIV drug treatment, especially protease inhibitor therapy. Perhaps the most urgent research objective is to design and implement studies on the cause(s) of metabolic abnormalities. Development of a consensus case definition of the syndrome is also of primary importance, so that study results can be compared.

Although preliminary efforts are underway to understand the syndrome better, there is a bewildering lack of urgency on the part of industry and the government for moving the appropriate research forward quickly and decisively. Australian researchers led by Andrew Carr, MD, and David Cooper, MD, have described a hypothetical mechanism for the syndrome that could explain most of the observed effects, but the group's ideas require validation.

An October 1998 meeting organized by the Forum for Collaborative HIV Research in Washington, DC, concluded that a prevalence study is an important first step in understanding the syndrome. In addition, the AIDS Clinical Trials Group (ACTG) and the Terry Beirn Community Programs for Clinical Research in AIDS (CPCRA) are both starting long-term studies to determine how the syndrome relates to use of protease inhibitors or non-nucleoside reverse transcriptase inhibitors; however, data from these trials won't become available for at least three years.

Experimental Treatment Candidates

HIV community activists, advocates, and people who are experiencing the signs and symptoms of the new syndrome are clamoring for research into potential treatment for the associated problems. A few clinicians (most notably Gabriel Torres, MD, in New York City) have reported some success treating buffalo hump and protease paunch using recombinant human growth hormone (Serostim). Studies of the effect of growth hormone on body fat are ongoing. Other therapeutic options worthy of study include lipid-lowering drugs, anti-diabetes drugs, diet modification, and exercise. Undoubtedly other therapies are also suitable for study. What appears lacking among the drug companies and in government circles is the will and determination to implement a variety of treatment studies quickly.

What Can Be Done Now?

Patients and doctors should carefully weigh the benefits and risks of using protease inhibitors, especially in the case of people who are asymptomatic and at low risk for immediate disease progression. Protease-sparing regimens may be appropriate for some people with HIV, although a number of persons with symptoms of body fat redistribution have never used protease inhibitors. Severe loss of fat in the face and buffalo hump may be helped by cosmetic surgery, but may recur. However, removal of fat from the abdominal area through liposuction is dangerous and should not be attempted, due to the possibility of intestinal perforation or bleeding within the abdominal cavity.

Conflicting Views of the Syndrome's Importance

Some providers and researchers believe that the syndrome poses no major problems for people with HIV, and is not widespread enough to warrant serious concern. Combination therapy using protease inhibitors has resulted in significant improvement in quality of life, reduction in the incidence of debilitating opportunistic infections, and increased survival for people with AIDS. This unexplained new syndrome may be a major threat to these therapeutic advances. Some patients who are experiencing debilitating side effects have abandoned anti-HIV treatment altogether. Others have decided not to start treatment out of fear that they will develop disfiguring symptoms. If prevalence rates of the syndrome are found to approach those reported by Cooper and others (greater than 60% of protease inhibitor-treated persons), many individuals may decide to discontinue drug regimens that have served them well. Others who urgently require potent anti-HIV therapy may refuse it.

Meeting the Challenges

It is imperative that disbelieving providers, researchers, and drug manufacturers quickly abandon their denial that the syndrome is real. Research on several fronts -- case definition, prevalence, relation to protease inhibitor therapy, treatment -- must be adequately funded by government and industry and initiated as soon as possible. Failure to effectively address these issues in a timely manner threatens to diminish the clinical successes achieved by widespread use of HAART. Meeting the challenges posed by this unexpected and distressing phenomenon head-on and with utmost speed is undoubtedly the best strategy for the long-term benefit of people with HIV, providers, and industry alike.

Ronald Baker is the former Director of Treatment Advocacy at the San Francisco AIDS Foundation and the former Editor-in-Chief of BETA. He is currently publisher and editor-in-chief of HIV and Hepatitis.Com, a new internet publication on treatment for HIV and viral hepatitis (www.HIVandHepatitis.com).

DT 19990110
DOCN BE990102