Transcript Slide 1 – HIV Research Catalyst Forum

Decreasing Metabolic
Problems in People with HIVWhat you can do as an activist
Nelson Vergel
Program for Wellness Restoration
PoWeRUSA.org
Copyright © 2010 by Nelson Vergel
Protease Inhibitors: Insulin resistance, life style, genetics
30-50%
Zerit
AZT
ZERIT,AZT
Zerit
AZT
60%
Metabolic
Disorders
40-60 %
??
20-40 %
Zerit, DDI
<5%
Protease Inh.: Insulin
Resistance, family
history 10-15 %
HIV Lipodystrophy
Facial wasting
Buffalo hump
Fat & Muscle
Wasting of arms
Truncal obesity
Patient also has
hyperlipidemia
& diabetes
Regimen:
Crixivan+Zerit
+Epivir
1.5 years
CD4=300
VL= <400
Fat and Muscle
Wasting of legs
Carruthers Lipoatrophy Severity Scale
Stage 1
Stage 3
James J et al. Dermatol Surg. 2002;28:979986.
Stage 2
Stage 4
Lipoatrophy and Venomegaly
Source: Body Positive Wellness Center- Houston
What Have We Learned Since 1997 ?
Effects of HIV Treatments on Lipids
Class
Drug
LDL
TG/VLDL
HDL
PI
RTV
 ()


LPVr



IDV



APV



NFV



ATV



EFV



NVP



d4T
?

TDF

?
NNRTI
NRTI
Maraviroc and Raltegravir do not seem to have much of an
effect on lipids
Grunfeld C. Disturbances in lipid and glucose metabolism in HIV infection.
AHA/AAHIVM Conference; 2007. Chicago.
Lipid Impact of PIs Largely Depends
on Norvir-Boosting Dose
ATV
ATV/r
(100 mg/d)
NFV
LPV/r
(200 mg/d)
FPV
FPV/r
(100 mg/d)
SQV/r
(200 mg/d)
FPV/r
(200 mg/d)
DRV/r
(200 mg/d)
In parentheses, daily ritonavir dose
TPV/r
(400 mg/d)
HIV Medications and Lipoatropy
(Fat Wasting)
Low Risk
Higher Risk
Nevirapine- Viramune
Stavudine-D4T
Atripla
AZT
Didanosine-DDI?
Lipoatrophy
Fat Wasting
TenofovirViread/Truvada
Abacavir- Ziagen
Lamivudine- 3TC
Emtricitabine- Emtriva
Fuzeon
Isentress
Selzentry
All protease inhibitors
DAD Study:
Lipodystrophy Incidence 2000-2002 vs 2003-2006
2000-2002
2003-2006
Lipoatrophy Deficits Requiring Correction
Temple
Fill
Cheek
Augmentation
Commonly Used Options for
HIV-related Facial Lipoatrophy
Product
Type/Sessions
Sculptra
(New Fill-PolyLactic
Acid)
Non- permanent
Radiesse
Calcium hydroxylapitite
(CaHA) microspheres
Non- permanent
(From FacialWasting.org)
Approved?
Cost
FDA approved
Patient Assistance for Product only
(under $40,000 a year income)
http://www.needymeds.com/papfor
ms/sculpt1039.pdf
.Labor cost avg. $400 per session.
Full price: $1,100 per session for
product.
FDA approved
Patient Assistance Available
3-7 sessions needed
http://www.radiessefl.com/Physician-section/Patientaccess-program/
2-3 sessions needed
Full Price: $1,200 per session.
Silikon 1000
Microdroplets
Permanent
4-6 sessions needed
PMMA
polymethylmethacrylate
Permanent
1-2 sessions needed
Off label useFDA approved for
intraocular injections
to treat CMV- related
retinal detachment
No Patient Assistance$600-800 per session
Not FDA approvedMexico, Brazil.
US version approved
for cosmetics: Artefill
but too expensive for
volume required
$2,000 avg. total cost for total
reconstruction. Patient
assistance in Tijuana:
www.MedicalPMMA.com
Proposed Decision Memo for Dermal injections
for the treatment of facial lipodystrophy
syndrome (FLS) (Jan 2010)
“Dermal injections for facial lipodystrophy
syndrome are only reasonable and necessary
using dermal fillers approved by FDA for this
purpose, and then only in HIV infected
beneficiaries who manifest depression
secondary to the physical stigmata of HIV
treatment. All other indications are
noncovered.”
Buttock Lipoatrophy:
Common Unaddressed Complaint
Visceral Fat Reduction
Potential Interventions for Decreasing
Abdominal Fat (visceral adipose tissue-VAT)


Diet- Lower carb?- No data available in HIV
Exercise- cardiovascular and resistance training- Some pilot

data with good results
Weight reduction- non HIV data

Anti-diabetic drugs: Metformin (Glucophage)- conflicting and
inconclusive data

Testosterone gel- subcutaneous fat loss only
Anabolic steroids- Oxandrin, nandrolone?- limited VAT data
Human Growth Hormone (Serostim)- highly effective. FDA

Human Growth Hormone Releasing Hormone- Tesamorelin-




declined approval due to side effects
Not approved yet- Pending issues. Slow action
Modification or cessation of HAART?- Not effective
Surgery- Liposuction of visceral fat very difficult and risky
Egrifta (Tesamorelin )
Growth Hormone
Releasing
(Upcoming
Potential FDA
Approval forHormone
Belly Fat Reduction)
(TH9507) vs Placebo
•2 mg injections under the skin every day. Effect disappears when stopped
•Uncertain if insurance companies, Medicare and ADAPs will cover it
•A patient assistance program is being designed
Reduced Bone Mineral Density in HIV+Slide 21
Patients
Yin et al, 2005
Teichman et al, 2003
Tebas et al, 2000
Madeddu et al, 2004
Loiseau-Peres et al, 2002
Knobel et al, 2001
Huang et al, 2002
Dolan et al, 2004
Bruera et al, 2003
Brown et al, 2004
Amiel et al, 2004
0%
20%
40%
HIV-positive
60%
80%
100%
HIV-negative
 risk with  age,  duration HIV infection and  CD4 nadir
Brown TT & Qaqish RB. AIDS. 2006; 20:2165-2174. Overton T et al. CROI 2007. Abstract 836
From MB Goetz, MD, at Los Angeles, CA: February 23, 2009, IAS–USA.
Slide 15
‘Fragility Fractures’ by Sex,
Age, and HIV Status
Women
Men
Includes fractures caused by violent injury. Not adjusted for Body
Mass Index, smoking, alcohol, prior fracture, functional status or
BMD. Triant VA. J Clin Edocrinol Metab 93:3499-3504, 2008
Should Dual Energy X-ray Absorptiometry
(DEXA) Be Used in HIV Aging Patients?
•
•
•
•
•
Developed to measure bone density
Can measure bone density, non-bone density, and fat density
Standard assessment for limb fat (normal >7 kg-8 kg)
Does not tell if truncal fat is subcutaneous or visceral
Comparison
– Error = ±1%-5%
• Software and calibration
• Body sections differences
– $150-$300
– Quick, subject-friendly
– Low radiation exposure
High Prevalence of Vitamin D
Deficiency in HIV Infection
• Retrospective seasonal
analysis of Vitamin D
deficiency within Swiss
cohort
• Started ARV in: Fall
(n=108); Spring (n=103)
− 75% men; age = 37; White =
87%; CD4+ 227; BMI = 22.9
− ARVs: TDF – 17%;
NNRTIs – 43%; PI -56%
• Conclusions
− Vitamin D deficiency is
common, but seasonal
− Blacks are at increased risk
− NNRTI use a risk factor
Vitamin D Deficiency is Not Influenced By ART
Fall
(n=108)
Spring
(n=103)
14%
42%
Insufficiency
62%
53%
Target Level
24%
5%
14%
47%
Insufficiency
63%
48%
Target Level
23%
5%
18%
52%
Insufficiency
59%
38%
Target Level
23%
10%
Baseline before cART
Vitamin D Deficiency
12 Months after cART Start
Vitamin D Deficiency
18 Months after cART Start
Vitamin D Deficiency
Deficiency <30 nmol/L
Target
≥75 nmol/L
Mueller N, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 752.
Alendronate for HIV-associated
osteopenia: 48 week results
6
% change from baseline in BMD
• N=31 HIV-infected subjects on
HAART with lumbar spine BMD
t scores less than -1.0
• 87% male, 80% caucasian, 29%
smokers, mean age 44yo; mean
BMI 25kg/m2
• median CD4 count 561
cells/microliter; 84% had VL <
400 copies/mL
• randomized to alendronate 70mg
weekly (n=15) or placebo (n=16)
• all patients received calcium 1g
daily and vit D 400IU daily
• no serious adverse events
p = 0.005
placebo
alendronate
5
4
3
p = NS
2
1
0
Spine
Mondy K et al. 10th CROI, Boston, 2003. Abstract 134.
Hip
What Can You Do to Help NOW?
Follow Nelson’s blog : survivingHIV.blogspot.com for all of the
following action items:
 Sign a letter to advocate for the inclusion of HIV as a risk factor
for bone density testing for those under 50 years of age.
 Monitor how Medicare will set up reimbursement of product and
labor for lipoatrophy correction. Follow up petitions may be
needed if this process is not done well.
 Advocate for interventional therapeutic studies to reverse bone
loss in HIV (vitamin D/calcium, prescription drugs, exercise,
hormones). Letters to private investigators, ACTG?
 Monitor how Egrifta’s reimbursement or patient assistance
program is set up if approved for visceral fat reduction.
 Advocate for research on the use of permanent facial
lipoatrophy options like Artefill.
What Can You Do to Help NOW?
 Advocate for research on the use of leptin to decrease
visceral fat.
 Advocate for the FDA to require small sub -studies to
study metabolic and body effects of drugs before approval
(Phase 4 studies take too long or are never done)
 Advocate for exercise/diet, vitamin D research to the NIH
and private investigators in your area. Lower glycemic
index diets have not been investigated in HIV. Also, help
create and advocate for wellness programs that include
comprehensive approaches (diet/exercise, smoking
cessation, patient empowerment)
 Educate your peers about metabolic issues related to
different HIV medications (lipids, fat gain/loss, bone) to
passify fears of naïve patients
 Keep reminding investigators and congress people that
physical changes in HIV are disease or drug related!
What you can do for YOU:
• Manage your lipids by natural ways, with HIV medication
changes and/or lipid lowering medications.
• Avoid Zerit , AZT, and higher doses of Norvir if you can
• Try to minimize sugars and processed carbs to your best
abilities
• Maximize soluble fiber (fruits & vegetables), lean protein and
good fats
• Exercise 3 to 4 times a week for an hour combining
resistance and cardiovascular exercise
• Take a vitamin complex twice a day
• Check your hormones and supplement if needed
• Research your hump liposuction and facial reconstruction
options before making a decision
• Stop smoking if you do. Minimize alcohol to 1-2 drinks a
day max.
• Email:
For More Information
[email protected]
• Websites: www.powerusa.org
•
www.medibolics.com
www.facialwasting.org
• Internet Discussion Group: send a blank email to
[email protected]