10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 6-8 November 2008, London, UK

GREATER LIMB FAT INCREASE WITH INTERMITTENT (RELATIVE TO CONTINUOUS) THYMIDINE-SPARING ANTIRETROVIRAL THERAPY IN HIV-INFECTED PATIENTS WITH LIPOATROPHY

Antiviral Therapy 2008; 13(Suppl. 4):A9 (abstract no. O-11)

E Martínez, A Milinkovic, F Garcia, E de Lazzari, M Larrousse, S Vidal, A León, M Lonca, M Laguno, M Martínez, M Calvo, JL Blanco, J Mallolas, JM Miró and JM Gatell
Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

BACKGROUND: Decreasing exposure to antiretroviral therapy (ART) might have favourable effects on HIV-associated lipoatrophy. We randomized HIV-infected patients with lipoatrophy receiving thymidine-containing ART to intermittent CD4- or HIV-1 RNA-guided thymidine-sparing ART or to continuous thymidine-sparing ART.

METHODS: Participants with moderate/severe lipoatrophy receiving thymidine-containing ART with >450 CD4/mm³ and HIV-1 RNA <200 copies/ml for ≥6 months were randomized to continue on ART switching from thymidine to non-thymidine nucleosides (control [C] group) or to stop ART until CD4 <350/mm³ (immune-guided [I] group) or HIV-1 RNA >30,000 copies/ml (viral-guided [V] group), then resuming ART for ≥3 months until CD4>450/mm³ and HIV-1 RNA<200 copies/ml and re-initiating the cycle again. Fasting metabolic parameters at least every 3 months and whole-body, femoral and lumbar spine DEXA scans at baseline, 12, and 24 months were assessed. Primary endpoint was limb fat change at 24 months. Treatment groups were compared by intention-to-treat for absolute and percent changes in fat, lipids and bone mineral density scores using linear and random-effects regression models.

RESULTS: There were 147 patients (median 39 years, 65% male, 17% hepatitis C+, 43% stavudine, 34% protease inhibitor and median CD4 753/mm³) randomized to C (n=44), I (n=53) or V (n=50) groups. Median baseline values of absolute and percent limb fat, triglycerides, total-LDL- and HDL-cholesterol were 4.1 kg, 15.2%, 134 mg/ dl, 219 mg/dl, 128 mg/dl and 51 mg/dl, respectively. By 24 months, 26% (I group) and 30% (V group) had re-initiated ART. Compared with C group, changes in absolute and percent limb fat in intermittent therapy groups at 24 months were +921 mg (I group, P=0.004) and +732 mg (V group, P=0.026) and +39% (I group, P=0.046) and +29% (V group, P=0.146), respectively. Factors independently associated with a greater (upper quartile) limb fat change were months off ART (per 3 months, adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02–1.12, P=0.006) and baseline trunk fat (per 100 g, adjusted OR 1.01, 95% CI 1.00–1.02, P=0.01). Relative to the C group, all plasma lipids significantly decreased in the I group, but not in the V group. Bone mineral density scores in femur and lumbar spine remained stable or increased in both intermittent ART groups, whereas they decreased in the C group. Five (5%) patients assigned to intermittent ART-experienced events leading to ART re-initiation because of acute retroviral syndrome, thrombocytopenia, psoriasis, hepatitis C reactivation and pregnancy. All patients in both intermittent groups were able to reach HIV-1 RNA <200 copies/ml on resuming ART.

CONCLUSION: In HIV-infected patients with lipoatrophy receiving thymidine-containing ART, intermittent thymidine-sparing ART leads to significantly greater increases in limb fat at 24 months than continuous thymidine-sparing ART.

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2008-11-06
O-11

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