The Body Covers: The 2nd International Workshop on Adverse Drug Reactions and Lipodystrophy Coverage
The 2nd International Workshop on Adverse Drug Reactions and Lipodystrophy
September 15, 2000
There were follow-ups of several switch studies confirming the results of preliminary presentations in other meetings. Rozenbaum presented the 48-week follow up of CNA30017 concerning switching PIs to abacavir showing improvements in insulin resistance and lipid parameters. Yarasheski presented data from their nevirapine cohort showing similar results: improvements in insulin resistance parameters, but lack of improvement of fat redistribution. He presented another poster showing an increase on lean body mass in patients who switched to nevirapine, an additional potential benefit of switching therapy.
Carr presented an update on the Australian switch showing worsening of peripheral fat lipoatrophy in patients who switched to a more intensive multinucleoside regimen.
Several posters dealt with efforts to "classify" the different phenotypes of lipodystrophy and metabolic abnormalities associated with HAART. There were posters form the Italian group (Lipodystrophy Italian Multicenter Study) (LIMS) and the Antiretroviral-associated Lipodystrophy European Collaborative Study (ALECS) group. It is important to know what we are talking about when we discuss the metabolic complications of antiretroviral treatment, and that our definitions are consistent. The problem of these multiple, and sometimes rather complicated classifications, is that they are not useful unless they are used by everybody, and they will be used by everybody only when there is a consensus between the different groups and countries. Until that happens, we can only watch from the sideline amused in how much effort is spent in trying to develop and memorize these incredibly complicated classifications. As an example, taken from one of the posters, a patient with a buffalo hump, increased abdominal fat, sunken cheeks, fat wasting, and triglycerides of 520mg/ml would be classified as type 3 B D, T2. Just try to remember that!
Several presentations focused on gender differences on lipodystrophy. Different factors seem to be associated with abnormal fat distribution in men and in women. Berger from Chicago and Colebunders from Belgium presented data on lipodystrophy in women and showed an increased incidence of this problem among them. Berger questioned the validity of some of the DEXA-derived ratios used to evaluate lipodystrophy when used in females. It is obvious that more research is needed in females with HIV infection and metabolic problems.
In another poster, McComsey looked at the use of anabolic agents. Besides being used by many athletes in this Olympic year, anabolic agents have been used extensively in HIV therapy for the treatment of wasting syndrome. Anabolic agents stimulate protein synthesis and increase lipid oxidation. Some authors have proposed using them as treatment for some metabolic abnormalities associated with the prolonged use of potent antiretroviral therapy. Three authors have anecdotal reports, and small uncontrolled trials of improvements in the fat redistribution syndrome with the use of these agents. However, no large randomized trials have been presented, so their role for this indication is still unclear. The most popular anabolic agents currently in use include growth hormone, oxandrolone and testosterone.
McComsey presented data from a large multicenter cross-sectional study looking at risk factors for the development of metabolic abnormalities (central obesity, peripheral lipoatrophy, and lipids and glucose metabolism), and trying to relate it to the use of anabolic agents (oxandrolone [28 patients], oxandrolone plus testosterone [23 patients], testosterone alone [58 patients] and growth hormone [58 patients]). They used DEXA to look at differences in fat redistribution between the groups using anabolic agents, and a matched control group not taking these agents. They could not find significant differences between them.
The problem with this design is that it tends to underestimate any therapeutic effect of these agents, because, at least in some cases, they were used to treat lipodystrophy itself. So, it should be expected that the patients taking them would have a "worse" phenotype than the individuals that were never put on them to start with. The role of anabolic agents in the management of the very frequent metabolic complications of antiretroviral therapy will have to come from prospective randomized trials.
All in all this was a better meeting than last year. The plenary talks were excellent and, I think, overall, the studies were more rigorous and focused. We are starting to better understand the mechanisms of metabolic complications associated with antiretroviral therapy and that not all drugs are created equal. There is still a long way to go, but there have been significant advances in our understanding of the metabolic complications of HIV.
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