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6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV25–28 October 2004 - Washington, DC, USA |
OBJECTIVE EVALUATION OF HIV LIPODYSTROPHY CASE DEFINITION IN A RANDOMIZED 96 WEEK CLINICAL TRIAL
Antiviral Therapy 2004; 9(6):L8 (abstract no. 11)
MG Law1, A Cheng2, DA Cooper1,3 and A Carr3
1National Centre in HIV Epidemiology and Clinical Research, UNSW, Sydney, Australia; 2Gilead Sciences, Foster City, Calif., USA; and 3St Vincent's Hospital, Sydney, Australia
INTRODUCTION: An objective definition of HIV lipodystrophy has been developed by the Lipodystrophy Case Definition Study Group, but the definition has not been evaluated based on prospective data. Gilead 903 was a randomized, double-blind clinical trial comparing stavudine (d4T) with tenofovir (TDF), both in combination with lamivudine and efavirenz in 600 treatment-naïve adults. Lipodystrophy was reported as an unprompted adverse event for 12% of patients randomized to d4T compared with 1% of TDF patients.
METHODS: DEXA scans were assessed and centrally read at 96 weeks in a subset of patients in Gilead 903. An adapted version of the lipodystrophy case definition based on centrally read DEXA scans, not including CT scans and waist to hip ratio in the definition (variables that were both unavailable in Gilead 903) was used to objectively define lipodystrophy. The accuracy of the adapted and original case definition models was 78% and 79%, respectively. Rates of lipodystrophy by the modified case definition were compared with rates diagnosed through unprompted adverse event reports. Risk factors for objectively defined lipodystrophy at week 96 using the modified case definition were identified using logistic regression.
RESULTS: 255 (43%) patients in Gilead 903 had DEXA scan and other data available for the adapted case definition. Of these patients, 17 (7%) reported lipodystrophy as an unprompted adverse event by week 96. The case definition identified a total of 48 (19%) patients with lipodystrophy, 40 (31%) receiving d4T and eight (6%) receiving TDF. Of these 48 patients, only seven (15%) also reported lipodystrophy as an adverse event. In multivariate analyses, objectively defined lipodystrophy was associated with d4T vs TDF [odds ratio (OR)=8.7, P<0.001], older age (OR=1.08 per year, P=0.001), female versus male (OR=3.7, P=0.001) and higher baseline triglycerides (OR=1.32 per mmol/l, P=0.021).
CONCLUSIONS: An adapted objective lipodystrophy case definition was more sensitive for diagnosing lipodystrophy in Gilead 903 than unprompted adverse event reports.
2004-10-25
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