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UK-CAB November 2005 Feedback from 7th Lipodystrophy Workshop 13-16 November, Dublin

UK-CAB November 2005 Feedback from 7th Lipodystrophy Workshop 13-16 November, Dublin. Overview. • Treatments: uridine, pravastatin, facial fat after switch, Niacin ER, buttock implants, • Other: monitoring access programmes, Polypill, NVP and brown fat, heart disease

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UK-CAB November 2005 Feedback from 7th Lipodystrophy Workshop 13-16 November, Dublin

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  1. UK-CAB November 2005 Feedback from 7th Lipodystrophy Workshop 13-16 November, Dublin

  2. Overview • Treatments: uridine, pravastatin, facial fat after switch, Niacin ER, buttock implants, • Other: monitoring access programmes, Polypill, NVP and brown fat, heart disease • Mechanisms: are fat loss and fat accumulation caused by a single process; nevirapine and brown fat • Q&As throughout please

  3. Treatments/Interventions • Uridine - for people on AZT or d4T • Pravastatin - showed fat return • Niacin ER - no reduction in VAT • Switch - RAVE analysis showed return of facial fat • Buttock implants - first reports - not a simple process

  4. Uridine (NucleomaxX) • Randomised trial: 36g, 3x day for first 10 days of each month, for 3 months @ ~£60/month • 20 people on d4T- or AZT-regimens randomised to NucleomaxX or placebo • Limb fat, total fat and intra-abdominal fat all inc. vs placebo and baseline (~400-1600g) • HDL fell (1.24 to 1.15mmol/). No effect on TG, lactates and insulin resistance (Sutinen et al. Abs 7) • Study 2: 16 pts, 36gTID every other day for 16 wks - no∆ mtDNA in fat or PBMC, only pt and doc survey (MacComsey et al. Abs 82)

  5. Pravastatin • 33 men on stable PI; TC>6.5 (median =7.6) • 4 week dietary advice: randomised to PVS (40mg/day) or placebo for 16 weeks • No change AUC cholesterol from baseline • Modest changes from week 4 • Total fat and limb fat both increase and % IAF decreased (Malon et al. Abs 23)

  6. Pravastatin PVS placebo p Chol AUC 0-16 week - 0.6 -0.4 0.8 Chol AUC 4-16 week - 0.82 -0.34 0.04 Total fat kg + 1.03 -0.09 0.01 Limb fat kg + 0.72 +0.19 0.04 % IAF - 2.9 0.08 0.7 (Mallon et al. Abs 23)

  7. Switch (RAVE) • Sub-study (n=47) from UK RAVE study: switch from AZT or d4T to TDF (n=23) or ABC (n=24) • 39/47 with facial LA at baseline; no reported benefit from pts in either arm • Mean volume difference (3D scan) at wk 48 was +2539mm3 (both cheeks) and +0.36kg (limb fat change, DEXA) • Correlation between increases in cheek and limb; no differences between TDF and ABC (Benn et al. Abs 8)

  8. Niacin ER • 48-wk multi-centre open label study in 33 men with TG >200mg/dl (67% white) • 500mg titrations every 4-6 weeks up to target 2000mg/day (n=23 reached 2000mg/day; 8 reached 1500mg/day) • No reduction seen in VAT (not in abstract) • Caution careful monitoring for glucose regulation and liver (Dubé et al. Abs 12)

  9. Niacin ER baseline %∆wk24 %∆wk48 Total-C 6.5 -0.6 -0.12 * HDL-C 0.9 +0.08 +0.13 * TG 5.6 -0.8 -0.5 * Non-HDL-C 5.4 -2.0 -1.7 * * P <0.01 (Dubé et al. Abs 12)

  10. Buttock implants • Spanish plastic surgery dept • Rarely reported at Lipo Workshops • Report on 7 women • Used silicone implants, placed inside muscle • Satisfied by results but no with contrast to thin legs • MRI scans for safety - will require replacement (Fontdevila et al. Abs 41)

  11. Other • Monitoring access programmes www.hivforum.org • Monitoring side effects: harm vs safety • Polypill - INSIGHT group (ld aspirin, lisinopril (ACE inhibitor to lower BP), hydrochlorithiazide (diuretic), pravastatin (cholesterol lowering). • nevirapine and brown fat • Risk of cardiovascular disease

  12. Single mechanism? • Reversal of fat loss also increased intra-abdominal fat (IAF - also known as VAT = visceral adipose tissue) • Analysed lipoatrophy studies: MITOX (and ROSEY) - male, 72 weeks, symptomatic lipoatrophy, DEXA • If limb fat increased, VAT tended to increase. • If VAT decreased, limb fat tended to decrease. • Different risk factors (Wand et al. Abs 3)

  13. NVP brown fat gene expression White fat cell Brown fat cell

  14. NVP brown fat gene expression • Biopsies from lipoma from HIV- and HIV+ +/- HAART • In vitro study of brown pre-adipocytes in culture exposed to individual ARVs • Gene expression related to brown fat was then measured in cultures and biopsies • Gene for preferentially expressing brown fat partially determined in lipoma, and markers (UCP-1) were activated by d4T and nevirapine (and suppressed by efavirenz, nelfinavir, saquinavir)

  15. Incremental risk of heart disease Dyslipideamia Hypertension x 2.3 x 1.5 x 3.5 x 5.9 x 2.7 x 3.9 x 1.7 Smoking

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