Unusual distributions of body fat in AIDS patients: A review of adverse events reported to the Food and Drug Administration

This report summarizes postmarketing adverse events reported to the Food an d Drug Administration (FDA) that describe unusual or abnormal fat distribut ion in association with anti-retroviral therapies. Reports associated will protease inhibitors were compared to those associated with non-protease inh ibitor antiretroviral therapies. The Spontaneous Reporting System (SRS) and Adverse Event Reporting System (AERS) of the FDA MEDWATCH postmarketing su rveillance system served as the database. Four protease inhibitors (saquina vir, indinavir, nelfinavir, and ritonavir) and seven nonprotease inhibitors (zidovudine, didanosine, zalcitabine, stavudine, lamivudine, nevirapine, a nd delavirdine) were searched for reports relating to: weight increase, unu sual fat deposition, Gushing's syndrome, or Cushingoid appearance. Each dru g was searched for its "life" from time of initial approval through a unifo rm database cutoff of March 18, 1998. A total of 62 cases of abnormal fat a ccumulation were reported in association with one or several of the four ap proved protease inhibitors compared to three cases reported in association with the seven non-protease inhibitor based therapies. Case descriptions va ried, and included abdominal fat accumulation, breast enlargement, thick ne cks, buffalo humps, multiple lipomatous growths, Cushingoid features, centr alized fat redistribution, and mesenteric, omental, and retroperitoneal fat accumulation. Some subjects switched or stopped their antiretroviral thera py, others underwent surgery to remove the fat, and many considered their s ymptoms disabling. The pathophysiologic mechanism for these events remains unclear and a causal link to a specific drug or drug class is uncertain. Pa tients and clinicians reporting to the MEDWATCH system, however, have clear ly associated the development of abnormal body fat with protease inhibitors as opposed to other antiretroviral therapies.