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Effects of tipranavir/r in comparison with lopinavir/r on changes in body composition and metabolic parameters in ARV-naive patients over 48 weeks
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Andrew Carr1, Armin Ritzhaupt2, Wei Zhang3,
Roberto Zajdenverg4, Cassy Workman5, Jose Gatell6,
Pedro Cahn7, Ricardo Chaves2
1. St Vincent's Hospital, Sydney, Australia; 2. Boehringer Ingelheim Pharma GmbH & Co., Biberach an der Riss, Germany; 3. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 4. Projeto Praça Onze - UFRJ Hospital Escola Sao Francisco de Assis, Rio de Janeiro, Brazil; 5. AIDS Research Initiative, Darlinghurst, Australia; 6. Hospital Clinic de Barcelona, Barcelona, Spain; 7. Fundacion Huesped, Buenos Aires, Argentina
"No study has reported on both body composition and insulin resistance in ART-naive patients initiating ART including a non-tNRTI and a boosted PI"
AUTHOR SUMMARY
TPV/r or LPV/r, with TDF-3TC, for 48 weeks:
- increased limb fat mass
- did not induce visceral adiposity
- did not alter trunk : limb fat ratio
- was not associated with insulin resistance
Greater effects of LPV/r on peripheral fat
A positive correlation was found between changes in limb fat and in VAT - this would be expected in a wasted person who gains weight
As limb fat loss, VAT and insulin resistance were not seen, it is possible that patients receiving PIs but who do not become lipodystrophic do not develop insulin resistance
Plasma adiponectin levels increased in all groups
Similar outcomes seen in healthy volunteers: four weeks of LPV/r or IDV increased adiponectin and lipid levels, whereas a single dose of LPV/r or IDV increased lipids without affecting adiponectin levels (1)
The increases in adiponectin levels we observed may, therefore, be a compensatory response to the metabolic effects of both PIs
Plasma leptin levels increased significantly more in the LPV/r arm and were strongly correlated with increases in limb fat mass
Background: TPV/r vs LPV/r in ARV-naive adults
Protease inhibitor (PI)-based and thymidine NRTI-based ART have been associated with progressive lipoatrophy, relative central fat accumulation, insulin resistance and type 2 diabetes mellitus
Most data for central fat accumulation and insulin resistance have been obtained from case reports, cross-sectional studies or very short (≦4-week) studies in healthy volunteers
No study has reported on both body composition and insulin resistance in ART-naive patients initiating ART including a non-tNRTI and a boosted PI
BI 1182.33 compared the safety and efficacy of two ritonavir-boosted PIs, tipranavir/r and lopinavir/r, with tenofovir and lamivudine, in ARV-naive adults
Design: TPV/r vs LPV/r in ARV-naive adults
Participants randomized to TDF 300mg QD / 3TC 300mg QD +
-- tipranavir 500mg / ritonavir 200mg BD (TPV/r200)
-- tipranavir 500mg / ritonavir 100mg BD (TPV/r100)
-- lopinavir 400mg / ritonavir 100 mg BD (LPV/r100)
BI 1182.33 metabolic sub-study investigated
-- peripheral fat: DEXA baseline + week 48
-- visceral fat: L4 abdominal CT baseline + week 48
-- fasting metabolic parameters every 12 weeks
Primary analysis - comparisons of the changes in limb fat mass in the TPV/r200 and TPV/r100 groups to the change in the LPV/r group, using the Wilcoxon rank-sum test
Statistical significance - p<0.025 for pair-wise comparisons
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