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Abstract
Persistent reduction in peripheral glucose disposal starting prior to fat distribution changes, only during first line ART with AZT/3TC/LPV/r but not NVP/LPV/r, suggests contribution of AZT/3TC to insulin resistance by a body composition-independent mechanism
van Vonderen M.G.A.1, Blümer R.M.E.2, Hassink E.3, Sutinen J.4, Ackermans M.T.5, van Agtmael M.A.1, Yki-Jarvinen H.6, Danner S.A.1, Sauerwein H.P.2, Reiss P.7, and the MEDICLAS study group.
Objectives: Prospective evaluation of body composition and glucose metabolism comparing NRTI-containing and NRTI-sparing ART.
Methods: ART-naïve men were randomized to LPV/r(400/100mg bd)+AZT/3TC or LPV/r(533/133mg bd)+NVP. CT, DEXA and hyperinsulinemic euglycemic clamps (aimed at plasma insulin level 200 pmol/l) using stable isotopes were performed before and after 3, 12 and 24 months of ART. A mixed model repeated measures ITT analysis correcting for baseline differences was performed.
Results: Baseline age was 42±9 yrs, BMI 23.3±3.1 kg/m2, CD4 count 201±90 cells/ml, HIV-1 RNA 5±0.5 log10 c/ml (comparable between arms). LPV exposure was similar in both arms.
| | AZT/3TC/LPV/r | NVP/LPV/r | | | Baseline (n=11) | Month 3 (n=11) | Month 12 (n=11) | Month 24 (n=10) | Baseline (n=9) | Month 3 (n=8) | Month 12 (n=9) | Month 24 (n=7) | | Limb fat (kg) | 6.6±0.3 | 6.8±0.3 | 6.4±0.3 | 5.9±0.3†# | 6.5±0.3 | 6.4±0.3 | 7.4±0.3 | 7.2±0.3 | | Total fat (kg) | 14.0±0.4 | 14.4±0.4# | 14.6±0.4 | 14.6±0.5† | 14.0±0.5 | 13.0±0.5 | 15.7±0.5 | 15.7±0.5* | | VAT (cm²) | 114±10.2 | 104 ±10.2 | 120±10.6 | 150±10.7* | 115±11.4 | 97 ±11.8 | 124±11.4 | 123±12.4 | | SAT/TAT | 0.54±0.02 | 0.56±0.02 | 0.55±0.02 | 0.50±0.02 | 0.53±0.02 | 0.53±0.02 | 0.53±0.02 | 0.56±0.02 | | Rd glucose (µmol/kg/min) | 23.1±1.6 | 17.5±1.6# | 19.3±1.6 | 19.7±1.7# | 22.5±1.7 | 23.6±1.9 | 21.0±1.7 | 25.3±1.9 | | Adiponectin (µg/ml) | 6.5±0.5 | 7.0±0.5 | 8.1±0.5 | 8.6±0.6*# | 6.4±0.6 | 7.7±0.6 | 9.9±0.6 | 10.8±0.7* |
Conclusions: The persistent decrease in insulin mediated glucose uptake observed only on AZT/3TC/LPV/r, starting already prior to measurable limb fat loss and visceral fat accumulation, suggests that AZT/3TC, independent of any GLUT-4 inhibition by LPV/r, contributes to peripheral insulin resistance by a mechanism which seems independent of changes in fat distribution. The observed adiponectin increases in both arms are remarkable given the reduced levels reported in patients with clinical lipoatrophy, and might suggest a compensatory response during the early phase of ART.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
Abstract no.
TUPEB077
Suggested Citation
"vanVonderenM.G.A., et al.
Persistent reduction in peripheral glucose disposal starting prior to fat distribution changes, only during first line ART with AZT/3TC/LPV/r but not NVP/LPV/r, suggests contribution of AZT/3TC to insulin resistance by a body composition-independent mechanism.
Poster exhibition:
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention:
Abstract no.
TUPEB077"
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