Fat redistribution in indinavir-treated patients with HIV infection: A review of postmarketing cases

Context: Fat redistribution (FR occurring alone or in association with hype rlipidemia has: been associated with protease inhibitors (PI) and nuclcosid e reverse transcriptase inhibitors (NRTIs); however, the relationship betwe en FR features, relationship of FR to hyperlipidemia, and pathogenesis of F R is unknown. Objective: To characterize the spectrum of FR, assess relationships among F R features, determine trends in occurrence of FR, and determine relationshi p of FR to hyperlipidemia. Design: Review of postmarketing indinavir reports of FR in Merck & Co. Inc. 's database. Setting and Participants: 282 reports of FR among HIV-positive patients tak ing indinavir submitted through the passive postmarketing system to Merck t hrough February 23, 1998. Results: 282 FR reports were compared across 3 groups: fat accumulation (FA ) only, FA with peripheral wasting (FA with PW), and peripheral wasting onl y (PWO). Of 282 reports, 56% (159 of 282) had FA only, 22% (63 of 282) had FA with PW, and 21% (60 of 282) had PWO. The proportions of reports of PWO was higher in men, whereas the proportion of reports of FA was higher in wo men. Blood lipids were provided in 93 of 282 reports: were elevated in 69 o f 93, and were normal in 24 of 93 reports. Proportions of hyperlipidemia an d hypertriglyceridemia reports were significantly higher in the PWO group v ersus FA only group (p = .024 and .003, respectively) and versus FA with/wi thout PW groups (p = .038 and .005, respectively). Weight gain was more fre quently reported in those with FA (100%) or FA with PW (68%), whereas weigh t loss was usually reported in those with PWO (83%). In all, 98% of patient s reporting FR on indinavir for whom a concomitant drug history was availab le were also taking lamivudine, stavudine, or both. A higher proportion of patients reporting PWO (34 of 60: 56.7%) versus FA (42 of 159; 26.4%) only took both lamivudine and stavudine. Conclusions: Differences observed from analysis of cases in clinical featur es, gender. weight change, concomitant medications, and presence of hyperli pidemia among the three groups of FR cases reported to Merck suggests that PWO may be a distinct entity from other features of FR. The data suggest th at certain antiretroviral combinations predispose HIV persons to developmen t of FR.