S.Collins HIV i-Base UK-CAB November 2005 Feedback from 7th Lipodystrophy Workshop 13-16 November, Dublin
Jan 17, 2016
S.Collins HIV i-Base
UK-CAB November 2005
UK-CABNovember 2005
Feedback from 7th Lipodystrophy Workshop
13-16 November, Dublin
S.Collins HIV i-Base
UK-CAB November 2005
• 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
Overview
S.Collins HIV i-Base
UK-CAB November 2005
• 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
Treatments/Interventions
S.Collins HIV i-Base
UK-CAB November 2005
• 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)
Uridine (NucleomaxX)
S.Collins HIV i-Base
UK-CAB November 2005
• 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)
Pravastatin
S.Collins HIV i-Base
UK-CAB November 2005
PVS placebo p
Chol AUC 0-16 week - 0.6 -0.4 0.8Chol AUC 4-16 week - 0.82 -0.34 0.04Total 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)
Pravastatin
S.Collins HIV i-Base
UK-CAB November 2005
• 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)
Switch (RAVE)
S.Collins HIV i-Base
UK-CAB November 2005
• 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)
Niacin ER
S.Collins HIV i-Base
UK-CAB November 2005
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)
Niacin ER
S.Collins HIV i-Base
UK-CAB November 2005
• 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)
Buttock implants
S.Collins HIV i-Base
UK-CAB November 2005
S.Collins HIV i-Base
UK-CAB November 2005
• 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
Other
S.Collins HIV i-Base
UK-CAB November 2005
• 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)
Single mechanism?
S.Collins HIV i-Base
UK-CAB November 2005
S.Collins HIV i-Base
UK-CAB November 2005
NVP brown fat gene expression
Brown fat cellWhite fat cell
S.Collins HIV i-Base
UK-CAB November 2005
• 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)
NVP brown fat gene expression
S.Collins HIV i-Base
UK-CAB November 2005
Incremental risk of heart disease
x 1.5 x 2.3x 3.5
x 3.9
x 5.9
x 2.7
x 1.7
Smoking
HypertensionDyslipideamia