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A Randomized, Multicenter Study of Protease Inhibitor (PI) Substitution in Aviremic Patients with Antiretroviral (ARV) Lipodystrophy Syndrome A. CARR*1 and D. A. COOPER1‚2.
1St. Vincent's Hosp.; 2Natl. Ctr. in HIV Epidemiology and Clin. Res., Sydney, Australia Background: LDS (peripheral lipoatrophy, central fat gain, insulin resistance, dyslipidaemia) often complicates PI-containing ARV therapy.
Methods: 80 PI recipients with lipodystrophy syndrome (LDS), no prior abacavir (ABV), NNRTI or adefovir (ADV), and plasma HIV RNA <400 copies/ml for >6 mths were randomized 2:3 to continue current therapy (n=31) or to continue nucleoside analogues and substitute PI(s) with ABV, nevirapine (NVP), ADV and hydroxyurea (HU) for 24 wks (n=49). Primary endpoints were HIV RNA and body composition (questionnaire, physical exam, DEXA, abdo L4 CT). Other assessments were safety, adverse events, biochemical, lipid and glycaemic parameters and CD4 counts.
Results: Mean baseline CD4 count was 450 cells/ml, and all but 2 pts were male. At week 24, 3 (6%) switch pts (vs 6 [19%] PI pts) had HIV RNA >50 copies/ml (p=0.14), despite AE-induced cessation of ADV (n=12), HU (n=8), ABV (n=3) and NVP (n=2) for mainly PRTD (ADV, n=8), nausea (HU, n=4) and hypersensitivity (ABV/NVP, n=3). CD4 counts fell a mean 70 cells/ml (p=0.002) in the switch group but there was no new AIDS condition in either group. One PI pt suffered a myocardial infarction. Central fat declined more in the switch group (1.1 vs 0.2 kg; p=0.049) as did total muscle mass. Switch pts, however, rated overall (p=0.008), central (p=0.001) and peripheral LD (p=0.07) as less severe at wk 24 than PI pts. Triglyceride, and total and LDL cholesterol, fell significantly (all p=0.001) in the switch group but C-peptide, insulin, insulin resistance (HOMA) and HDL cholesterol did not change.
Conclusions: PI(s) cessation and substitution with ABV/NVP/ADV/HU in heavily ARV-pretreated LDS pts maintained HIV RNA suppression, despite numerous switch drug AE-induced cessations. Switching led to reduced central fat and improvement of some lipid parameters, but decline in peripheral fat and overall muscle mass.
Key Words: LIPODYSTROPHY, PROTEASE INHIBITORS
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