1. Copyright © 2010 by Nelson Vergel Nelson Vergel Program for Wellness Restoration PoWeRUSA.org Decreasing Metabolic Problems in People with HIV- What you can do as an activist

2. Metabolic Disorders Protease Inhibitors: Insulin resistance, life style, genetics Zerit AZT ZERIT,AZT Protease Inh.: Insulin Resistance, family history Zerit, DDI ?? Zerit AZT 60% 30-50% 20-40 % 10-15 % 40-60 % < 5 %

3. HIV Lipodystrophy HIV Lipodystrophy Truncal obesity Facial wasting Wasting of arms Wasting of legs Patient also has hyperlipidemia & diabetes & diabetes Buffalo hump Regimen:Crixivan+Zerit+Epivir 1.5 years CD4=300 VL= <400 Fat and Muscle Fat & Muscle

4. Carruthers Lipoatrophy Severity Scale Stage 1 Stage 2 Stage 3 Stage 4 James J et al. Dermatol Surg. 2002;28:979- 986.

6. Lipoatrophy and Venomegaly Source: Body Positive Wellness Center- Houston

7. What Have We Learned Since 1997 ?

8. Effects of HIV Treatments on Lipids Grunfeld C. Disturbances in lipid and glucose metabolism in HIV infection. AHA/AAHIVM Conference; 2007. Chicago. ClassDrugLDLTG/VLDLHDL PIRTV  (  )      LPVr    IDV        APV    NFV      ATV  NNRTIEFV      NVP    NRTId4T ?? TDF  ?? Maraviroc and Raltegravir do not seem to have much of an effect on lipids

9. ATV ATV/r (100 mg/d) FPV/r (100 mg/d) NFV SQV/r (200 mg/d) LPV/r (200 mg/d) FPV/r (200 mg/d) DRV/r (200 mg/d) TPV/r (400 mg/d) FPV In parentheses, daily ritonavir dose Lipid Impact of PIs Largely Depends on Norvir-Boosting Dose

11. HIV Medications and Lipoatropy (Fat Wasting) Lipoatrophy Fat Wasting Higher Risk Stavudine-D4T AZT Didanosine-DDI? Low Risk Nevirapine- Viramune Atripla Tenofovir- Viread/Truvada Abacavir- Ziagen Lamivudine- 3TC Emtricitabine- Emtriva Fuzeon Isentress Selzentry All protease inhibitors

12. DAD Study: Lipodystrophy Incidence 2000-2002 vs 2003-2006 2000-2002 2003-2006

13. Temple Fill Cheek Augmentation Lipoatrophy Deficits Requiring Correction

14. Commonly Used Options for HIV-related Facial Lipoatrophy (From FacialWasting.org) ProductType/SessionsApproved?Cost Sculptra (New Fill-PolyLactic Acid) Non- permanent 3-7 sessions needed FDA approved Patient Assistance for Product only (under $40,000 a year income) http://www.needymeds.com/papfor ms/sculpt1039.pdf http://www.needymeds.com/papfor ms/sculpt1039.pdf http://www.needymeds.com/papfor ms/sculpt1039.pdf.Labor cost avg. $400 per session. Full price: $1,100 per session for product. Radiesse Calcium hydroxylapitite (CaHA) microspheres Non- permanent 2-3 sessions needed FDA approved Patient Assistance Available http://www.radiesse- fl.com/Physician-section/Patient- access-program/ http://www.radiesse- fl.com/Physician-section/Patient- access-program/ Full Price: $1,200 per session. Silikon 1000 MicrodropletsPermanent 4-6 sessions needed Off label use- FDA approved for intraocular injections to treat CMV- related retinal detachment No Patient Assistance- $600-800 per session PMMA polymethylmethacrylate Permanent 1-2 sessions needed Not FDA approved- Mexico, 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 www.MedicalPMMA.com

16. “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.” Proposed Decision Memo for Dermal injections for the treatment of facial lipodystrophy syndrome (FLS) (Jan 2010)

17. Buttock Lipoatrophy: Common Unaddressed Complaint

18. Visceral Fat Reduction

19. Potential Interventions for Decreasing Abdominal Fat (visceral adipose tissue-VAT) n Diet- Lower carb?- No data available in HIV n Exercise- cardiovascular and resistance training- Some pilot data with good results n Weight reduction- non HIV data n Anti-diabetic drugs: Metformin (Glucophage)- conflicting and inconclusive data n Testosterone gel- subcutaneous fat loss only n Anabolic steroids- Oxandrin, nandrolone?- limited VAT data n Human Growth Hormone (Serostim)- highly effective. FDA declined approval due to side effects n Human Growth Hormone Releasing Hormone- Tesamorelin- Not approved yet- Pending issues. Slow action n Modification or cessation of HAART?- Not effective n Surgery- Liposuction of visceral fat very difficult and risky

20. Growth Hormone Releasing Hormone (TH9507) vs Placebo Egrifta (Tesamorelin ) (Upcoming Potential FDA Approval for Belly Fat Reduction) 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

21. Reduced Bone Mineral Density in HIV+ Patients Brown TT & Qaqish RB. AIDS. 2006; 20:2165-2174. Overton T et al. CROI 2007. Abstract 836  risk with  age,  duration HIV infection and  CD4 nadir Slide 21 From MB Goetz, MD, at Los Angeles, CA: February 23, 2009, IAS–USA.

22. 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

23. 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

24. 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 Baseline before cART Fall (n=108) Spring (n=103) Vitamin D Deficiency14%42% Insufficiency62%53% Target Level24% 5% 12 Months after cART Start Vitamin D Deficiency14%47% Insufficiency63%48% Target Level23% 5% 18 Months after cART Start Vitamin D Deficiency18%52% Insufficiency59%38% Target Level23%10% Deficiency <30 nmol/L Target ≥75 nmol/L Mueller N, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 752.

25. Alendronate for HIV-associated osteopenia: 48 week results 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 % change from baseline in BMD Mondy K et al. 10th CROI, Boston, 2003. Abstract 134. p = NS

26. 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.

27. 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! 

28. 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.

29. For More Information For More Information Email: Email:Nelsonvergel@yahoo.com Websites: www.powerusa.org Websites: www.powerusa.orgwww.powerusa.org www.medibolics.com www.medibolics.comwww.medibolics.com www.facialwasting.org www.facialwasting.orgwww.facialwasting.org Internet Discussion Group: send a blank email to pozhealth-subscribe@yahoogroups.com Internet Discussion Group: send a blank email to pozhealth-subscribe@yahoogroups.com