December 18, 2001
"Meet the Experts" sessions "permit conference attendees to interact directly with two specialists on a topic." Or so says the description in the ICAAC program guide. Sounds like a great idea. However the devil is always in the details. Certainly Drs. Currier and Powderly are experts on this topic. But problems arise: The audience is comprised of non-experts as well as experts. The discussion needs to be focused on the needs of both groups. So results tend to be mixed: The experts may be unsatisfied with too basic a discussion, while non-experts may not be up to a higher level of discussion. The setting needs to be conducive to interaction. Two speakers at a podium in a large room with a large number of attendees may not be able to facilitate much of a discussion. Suggestions from me to the ICAAC organizers: Utilize interactive technology to involve the attendees directly in the presentations, make sure the room is suitable -- today there was but one microphone for the audience and questions could not be heard throughout the room.
The session started with each expert giving a brief overview of their topics: Dr. Currier on lipid and glucose disorders and body habitus changes, Dr. Powderly on lactic acidosis and bone disorders. Dr. Currier attempted to discuss new information; Dr. Powderly gave more of an overview and review.
Lipid disorders are common in people with HIV and seem to be directly related to antiretroviral therapy. However, individuals may have factors contributing to the development of lipid disorders such as age, obesity, family history and lack of exercise. Dr. Currier discussed the guidelines for the evaluation and treatment of lipid disorders published by an ACTG committee and also mentioned individual treatment options such as statins and fibrates. It may seem obvious, but our concern regarding this topic should be about the likelihood of increased cardiovascular events as a consequence of hyperlipidemia. It is amazing to me how little scientific information is yet available on both the interventions and the consequences of lipid disorders in people with HIV. Indeed there was very little "new" information presented here today.
We now know that protease inhibitors have both direct and indirect effects on glucose metabolism. We believe that drugs such as metformin or the glitazones may have a beneficial effect. But again, the lack of truly pertinent information on prevention and treatment is extraordinary considering how common these abnormalities are in people with HIV. There is essentially no new information in this area also.
The most telling statements made by our experts today were that the prevention of these abnormalities may be more important than the treatment (Dr. Currier) and that no study yet demonstrates any significant or consistent regain of fat after its loss (Dr. Powderly). So Dr. Currier summarized the current state of knowledge emphasizing treatment options. But as readers of The Body are aware, there are no proven treatment interventions in this area.
Dr. Powderly stated that elevations in lactic acid are associated with NRTIs and that d4T and ddI were the NRTIs most commonly associated in most studies. However, he stressed several key points. Association with d4T/ddI does not mean that d4T/ddI cause these syndromes. In addition, elevations in lactic acidosis range from trivial to life-threatening -- and it is our responsibility to ascertain the difference. He said that there is not "any value in routinely measuring lactic acidosis," but that lactic acidosis should be evaluated when symptoms (fatigue, nausea and abdominal pain, for example) suggestive of these syndromes occur.
Osteonecrosis (or avascular necrosis) of the hip is a serious complication that has been reported in HIV patients. Fortunately, it is rare. It should be suspected when hip pain occurs in this setting. X-rays are not sufficient to make a diagnosis. Evaluation by MRI is much more sensitive and accurate. Treatment is always surgical.
Osteopenia/osteoporosis (or decreased bone density) seems to be much more common than osteonecrosis. A recent antiretroviral-naive study of tenofovir showed a baseline (prior to any antiretroviral therapy) osteopenia rate of 24 percent and osteoporosis of 2 percent. ART has indeed been shown to accelerate bone metabolism. Up to 50 percent of people on ART have abnormal bone density. But so what? Does it lead to bone fractures? Is it progressive? Is it clinically relevant? Well, we actually don't know yet. It takes years for osteopenia to cause fractures and we do not have that data yet. A study presented today at this meeting looked at the fracture rate in studies submitted to the FDA for new drug registration of antiretrovirals. Over 10,000 patient reports were reviewed. The overall fracture rate was 2 percent, essentially identical to that seen in control populations (without HIV). However, the duration of these studies was approximately one year, not long enough to realistically evaluate the risk of fractures related to reduced bone density. So, more studies of much longer duration are urgently needed.