M. Mann et al., Unusual distributions of body fat in AIDS patients: A review of adverse events reported to the Food and Drug Administration, AIDS PAT CA, 13(5), 1999, pp. 287-295
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.