Easy to understand, comprehensive overview of fat loss in HIV disease. Answers 3 key questions: What?...Why?....How?

1. © Visionary Health Concepts, New York 2007 Released October 5, 2007

3. The What, the Why, and the How of Lipoatrophy in HIV CEU Information Accreditation Statement(s): ANCC Medical Education Collaborative (MEC) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. RNs, LPNs, LVNs and NPs can receive up to .7 contact hours for participation in this program. This program is cosponsored with Medical Education Collaborative, Inc. (MEC) and Visionary Health Concepts. Provider approved by the California Board of Registered Nursing, Provider Number CEP 12990, for .8 contact hour(s). Joint Sponsor This activity is joint sponsored by Visionary Health Concepts and Medical Education Collaborative (MEC). MEC is a non-profit organization that has been certifying quality educational activities since 1988. Commercial Support This activity was made possible by an educational grant from Abbott Laboratories.

6. Faculty Disclosures The planning committee and faculty members have the following disclosures: CEU Chairperson Andrew Carr, MBBS, MD, FRACP, FRCPA St. Vincent's Hospital; Professor of Medicine, University of New South Wales, Sydney, Australia Dr. Andrew Carr has the following relationships to disclose: grants for paid research, speaker’s bureau and advisory boards from Abbott Laboratories. Editor Maggie Sosa, APRN, BC, AACRN, ACHPNNP Nurse Practitioner, Broadway House for Continuing Care, Newark, NJ, USA Maggie Sosa has no relationships to disclose. The What, the Why, and the How of Lipoatrophy in HIV CEU Information

7. Faculty Disclosures continued Writers Lillian Thiemann President, Visionary Health Concepts, Gardiner, NY, USA Lillian Thiemann has no relationships to disclose. Deneen Robinson Savant Consultants, Dallas TX, USA Deneen Robinson has the following relationships to disclose: stock ownership: Abbott Laboratories; advisory committee: Bristol-Myers Squibb; speaker’s bureau: Gilead Sciences. Accredited Provider The employees of Medical Education Collaborative, the accredited provider for this activity, have no significant relationships to disclose. The What, the Why, and the How of Lipoatrophy in HIV CEU Information

10. Antiretroviral therapy extends life Percentage of persons surviving through June 2005, by years after acquired immunodeficiency syndrome (AIDS) diagnosis cohorts during 1981-2003 and by year of diagnosis--United States [Centers for Disease Control and Prevention 2005]

11. WWW.FREEHIV.COM DRUG CHART Currently-approved HIV medications Easy-to-print version available at www.freehivinfo.com NRTI, NtRTI - Nucleoside and or Nucleotide Reverse Transcriptase Inhibitors (nukes) Brand name (generic name, abbreviation) Picture Year approved Retrovir ® (zidovudine, AZT) 1987 Videx ® (didanosine; ddI): buffered versions 1991 Zerit ® (stavudine; d4T) 1994 Epivir ® (lamivudine; 3TC) 1995 Combivir ® (Retrovir + Epivir, CBV) 1997 Ziagen ® (abacavir, ABC) 1998 Trizivir ® (Retrovir + Epivir + Ziagen) 2000 Videx ® EC (didanosine; ddI): delayed-release capsules 2000 Viread ® (tenofovir DF, TDF) 2001 Emtriva ® (emtricitabine, FTC) 2003 NNRTI - Nonnucleoside Reverse Transcriptase Inhibitors (non-nukes) Brand name (generic name, abbreviation) Picture Year approved Viramune ® (nevirapine, NVP) 1996 Rescriptor ® (delavirdine, DLV) 1997 Sustiva ® (efavirenz, EFV) 1998 Atripla™ (Sustiva* + Viread + Emtriva), * Viread and Emtirvia are non-nucleoside reverse transcriptase inhibitors (NRTIs). 2006 Crixivan ® (indinavir, IDV) 1996 Norvir ® (ritonavir, RTV) 1996 Viracept ® (nelfinavir, NFV) 1997 Kaletra ® (lopinavir + ritonavir, LPV/RTV) 2000 Lexiva ® (fosamprenavir, fos-APV) 2003 Reyataz ® (atazanavir, ATV) 2003 Aptivus ® (tipranavir, TPV) 2005 Prezista™ (darunavir) 2006 Epzicom ® (Ziagen + Epivir) 2004 Truvada ® (Viread + Emtriva) 2004 Atripla™ (Sustiva* + Viread + Emtriva) * Sustiva is a non-nucleoside reverse transcriptase inhibitor (NNRTI) 2006 PI - Protease Inhibitors Brand name (generic name, abbreviation) Picture Year approved Invirase ® (saquinavir, SQV) 1995 Entry Inhibitors (including Fusion Inhibitors and CCR5 Antagonists) Brand name (generic name, abbreviation) Picture Year approved Fuzeon ® (enfuvirtide, T-20) 2003 Selzentry ® (maraviroc) 2007

13. Lipodystrophy umbrella

15. AIDS wasting is not lipoatrophy Fat loss Weight loss & diarrhea CD4 Count HIV under control? Associated with risk of death? Affects looks? AIDS Wasting yes yes Less than 50 No yes yes Lipoatrophy (fat loss) yes no Over 200 yes no yes

18. Examples of lipoatrophy (men)

19. Examples of lipoatrophy (women)

23. Families of HIV drugs: Nucleoside reverse transcriptase inhibitors (NRTIs) Brand name Generic name Image Atripla™ (Sustiva* + Viread + Emtriva) efavirienz + tenofovir + emtricitabine Combivir ® (Retrovir + Epivir) zidovudine + lamivudine Emtriva ® emtricitabine, FTC Epivir ® lamivudine; 3TC Retrovir ® zidovudine, AZT Trizivir ® (Retrovir, Epivir + Ziagen) zidovudine + lamivudine + abacavir Brand name Generic name Image Truvada ® (Viread + Emtriva tenofovir + emtricitabine Videx ® didanosine; ddI Videx ® EC didanosine; ddI Viread ® tenofovir DF, TDF Zerit ® stavudine; d4T Ziagen ® abacavir, ABC

25. Switching anti-HIV drugs Change from baseline (kg) Week Switching NRTIs d4T/AZT did help reverse the fat loss. However, there was no return to “normal”. [Carr et al, AIDS 2001] [Martin et al, AIDS 2004] [McComsey et al, Clin Infect Dis 2004] [Milinkovic et al, CROI 2005] [Carr et al, JAMA 2002] [ Moyle et al, CROI 2005] [Murphy et al, CROI 2005]

26. Families of HIV drugs: Non nucleoside reverse transcriptase inhibitors (NRTIS) Brand name Generic name Image Atripla™ (Sustiva* + Viread + Emtriva) efavirienz + tenofovir + emtricitabine Rescriptor ® delavirdine, DLV Sustiva ® efavirenz, EFV Viramune ® nevirapine, NVP

28. Families of HIV drugs: Protease Inhibitors (PIs) Brand name Generic name Image Aptivus ® tipranavir, TPV Crixivan ® indinavir, IDV Invirase ® saquinavir, SQV Kaletra ® lopinavir + ritonavir, LPV/RTV Lexiva ® fosamprenavir, fos-APV Brand name Generic name Image Norvir ® ritonavir, RTV Prezista™ darunavir, DRV Reyataz ® atazanavir, ATV Viracept ® nelfinavir, NFV

29. Families of HIV drugs: Entry Inhibitors Brand name Generic name Image Fuzeon ® enfuvirtide, ENF Selzentry ® maraviroc, MRV

33. Detecting fat loss

35. Self-reported fat loss 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 Upper Back Abdominal Fat Waist Chest Neck Legs Buttocks Arms Face Cheeks 0 Men Women HIV+ HIV- % Reporting Fat Loss % Reporting Fat Loss [FRAM Study Group. J Acquir Immune Defic Syndr. 2005;40:121-131.] [FRAM Study Group. J Acquir Immune Defic Syndr . 2006;42:562-571.]

38. Tools to measure fat loss (3) Skin-fold test A metal tool is used to “pinch” body tissue in several places. The measurements are compared to standards. Requires a skilled technician. MRI (Magnetic Resonance Imaging) uses a magnetic field to create an image of the body showing the location and amount of fat; very expensive [Levine J et al. J Appl Physiol 2000;88:452.] [Kamel E. et al Obes Res 2000;8:36.] [Mitsiopouools J Appl Physiol 1998;85:115.]

41. So why does fat loss matter?

45. The goal is to look normal

46. Can’t we just take another pill? [Slam L, et al. 13th CROI 151LB.] [Cavalcanti RB, et al. and Grinspoon S et al. J Infect Dis .--both Published online , ahead of print (May 2, 2007).] [Mallon PWG et al. Antiviral Therapy 10: L5, 2005.] [Macallan, DC, et al.. 46th ICAAC. Abs H-1897.] ] Agents studied to try to increase fat Results Rosiglitazone Minimal effect and may hurt heart by raising cholesterol and triglycerides Pioglitazone In one study pioglitazone raised limb fat but only in those NOT taking Zerit (stavudine, d4T) Pravastatin Fat gains shown but the study was small, and of short (12W) duration Uridine NucleoMaxx® is EXPENSIVE! Fat gains shown but the study was small, and of short (12W) duration Human Growth Hormone Makes fat loss worse

48. Commonly-used options for HIV-related facial lipoatrophy Table provided by PoWeR (Program for Wellness Restoration) and www.facialwasting.org. Source: Comparison of Poly-L-lactic Acid and Calcium Hydroxylapatite for Treating Human Immunodeficiency Virus-Associated Facial Lipoatrophy; Cosmetic Dermatology, May 2007, Vol 20 No. 5 PRODUCT TYPE/SESSIONS FDA APPROVED? COST Sculptra (Poly-L-lactic acid) Non-permanent/ several sessions needed Yes Patient assistance for product only (under $40,000/yr income: www.needymeds.com/papforms/ sculpt1039.pdf ). Labor cost avg. $400 per session. Full price: $1100 per session for product. Radiesse (Calcium hydroxylapatite ) Non-permanent/ several sessions needed Yes Patient assistance for product only (under $80,000 a year w/sliding scale). Labor avg. $400 Full price: $1200 per session. Silikon 1000 (Purified polydimethyls-iloxane ) Permanent/ several sessions needed Off label use: FDA approved for intraocular injections to treat CMV- related retinal detachment No patient assistance available. Full price: $800 per session.

49. Commonly used options for HIV-related facial lipoatrophy (2) Table provided by PoWeR (Program for Wellness Restoration) and www.facialwasting.org. Source: Comparison of Poly-L-lactic Acid and Calcium Hydroxylapatite for Treating Human Immunodeficiency Virus-Associated Facial Lipoatrophy; Cosmetic Dermatology, May 2007, Vol 20 No. 5 PRODUCT TYPE/SESSIONS APPROVED? COST PMMA-polymethylmethacrylate Permanent/ 1-2 sessions needed Not FDA approved: Mexico, Brazil $1200 avg total cost Autologous fat transfer: fat pulled from one spot in the body and injected into the face Non-permanent/ several sessions needed FDA approved $3,000 avg total cost Hyaluronic Acid (Restylane, Perlane, Hylaform) Permanent/ several sessions needed Only Restylane is FDA approved Approximately $1,500 per visit Polyalkylimide ( Bioalcamid) Permanent/ several sessions needed Not FDA approved: Europe, Canada, Mexico, others $4,500 avg total

60. The What, the Why, and the How of Lipoatrophy in HIV Legal Disclaimer The material presented here does not necessarily reflect the views of Visionary Health Concepts or companies that support educational programming on www.freehivinfo.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity. Copyright © 2007 Visionary Health Concepts