LIPODYSTROPHY WORKSHOP
The 2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV was held prior to ICCAAC in Toronto on September 1315, 2000. Some of the key points from this meeting are reviewed below.
Bill Valeni, MD
The Australian Lipodystrophy Prevalence Survey
The Australian Lipodystrophy Syndrome Research Group reviewed the results of a 6 month cross-sectional survey through a national network of investigator sites in Australia. Among their findings by physician assessment were:
" 724 patients (54%) were noted to have lipodystrophy (LD).
" Both central fat accumulation and peripheral fat loss were predominant.
" The most frequently affected site is the face (45%), followed by the legs (43%), abdomen (39%), arms (38.5%), buttocks (36%), dorsocervical region (4%), and lipomata (4%).
There was a significant association between LD and other factors:
" Patients aged 4049 had a 2-fold increased risk of LD.
" Among patients aged >50, the risk of LD increased 4-fold.
" Patients with symptomatic disease (including AIDS) had a 2-fold increase in risk.
" Patients with HIV viral load >10,000 copies/mL had a 40% reduction in risk.
" No effect of CD4 T-cell count on risk of LD was noted.
" Increased exposure to both nucleoside reverse transcriptase inhibitors and HIV protease inhibitors was associated with significant increases in risk of LD.
" No effect on risk was seen with non-nucleoside reverse transcriptase inhibitor use, although the median length of exposure to this drug class was relatively short.
The survey noted the following associations between lipodystrophy and specific anti-HIV drugs:
" In patients with fat loss, there were significant associations seen with increased duration of therapy with Fortovase/ Invirase (saquinavir), Crixivan (indinavir), Viracept (nelfinavir), Hivid (zalcitabine, ddC), and Ziagen (abacavir).
" Fat accumulation was associated with an increased duration of therapy with Crixivan (indinavir), Zerit (stavudine, d4T), and Epivir (lamividine, 3TC).
The Causes of Lipodystrophy Are Multifactorial
In the Lipodystrophy Italian Multicenter Study (LIMS), metabolic and body-shape changes were seen in patients using different treatment regimens and with differing risk factors. As a result, the study investigators concluded that these changes could not be attributed to just one drug treatment, combination of drugs, or risk factor.
LIMS, one of the first large-scale studies to investigate the pathology of lipodystrophy, analyzed a cross-sectional multicenter study of 2,258 patients consecutively enrolled in six Italian clinical centers for 2 months and reported results in three studies.
Results from the three studies showed that factors such as age, sex, HIV viral load, and duration of treatment for HIV have an effect on metabolic and body-shape changes.
The first study looked at the risk factors associated with body-shape alterations. The results showed that the main risk factors associated with these alterations include duration of treatment, age, gender, and plasma viremia (HIV viral load level). The data suggest the increased risk of body-shape changes in patients with undetectable HIV viral load likely reflects a good adherence to anti-HIV therapy, and that different types of body-shape changes may be induced by changes in anti-HIV therapy.
Once risk factors were assessed, a second study examined what risk factors contributed to different types of metabolic and body-shape changes in people using anti-HIV therapy. The investigators use a four-part classification system and described the risk factors associated with each class (see Table 1).
The third study looked at the association between any of the four types of metabolic and body-shape changes and different treatment regimens.
The risk for all four types was significantly higher in patients treated with protease inhibitors. However, distinct metabolic and body-shape changes were observed in patients with a variety of treatment histories. The investigators cautioned that one specific drug or drug regimen is not responsible for metabolic and morphologic alterations in people with HIV. Physicians should continue to use all effective treatment strategies, and should pay particular attention to the individual therapeutic history and to careful patient monitoring.
The classification system used by the authors can help clinicians organize their thoughts on the syndrome(s) and perhaps can lead us toward a set of standard definitions.
Galli M et al. Risk of developing metabolic and morphological alterations under antiretroviral therapy according to the drug combinations. Lipodystrophy Italian Multicenter Study (LIMS). 2nd International Workshop on Adverse Drug Interactions and Lipodystrophy in HIV. September 1315, 2000, Toronto, Canada. Abstract P59.
Galli M et al. Risk factors associated with types of metabolic and morphological alterations according to the Marrakech classification. Lipodystrophy Italian Multicenter Study (LIMS). 2nd International Workshop on Adverse Drug Interactions and Lipodystrophy in HIV. September 1315, 2000, Toronto, Canada. Abstract P61.
Galli M et al. Factors associated with the development of body habitus alterations (BHA) and types of BHA associated with antiretroviral therapy (ART) changes in patients on treatment with antiretroviral drugs in the lipodystrophy multicenter study (LIMS). 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. September 1720, 2000. Toronto, Canada. Abstract 1284.
TAble 1. Four-part Classification System for Body Shape Changes in People using Anti-HIV therapy
Class Risk Factors
Type 1: fat loss treatment duration and age
Type 2: fat accumulation female sex
Type 3: combined forms treatment duration, female sex, age, undetectable viral load
Type 4: metabolic alterations male sex, treatment duration without body shape changes.
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