Aging Healthy While Surviving HIV


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Nelson Vergel from described the latest advances in HIV and aging research

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  • Background:  Tenofovir (TDF) is associated with renal phosphate wasting, elevation in markers of bone turnover, and decrease in bone density. Vitamin D3 (VITD) treatment increases renal tubular phosphate absorption in VITD deficiency. VITD deficiency/insufficiency (serum 25-OH VITD <30 ng/mL) occurs in >80% of HIV+ youth in the U.S. We hypothesized that VITD administration would increase tubular reabsorption of phosphate (TRP) and decrease serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C telopeptide (CTX) in HIV+ youth treated with TDF.Methods:  Randomized controlled trial (RCT) of VITD 50,000 IU vs placebo (PL) every 4 weeks for 12 weeks (3 directly observed oral doses) in HIV+ youth ages 18 to 24, viral load <5,000 copies/mL, and unchanged cART for ≥90 days. Participants were enrolled based on treatment with cART containing TDF (N = 118) or noTDF (N = 85) and randomized within those groups to VITD (N = 102) or PL (N = 101). Results:  At baseline, VITD and PL groups were similar in age, race/ethnicity, body mass index, VITD, and calcium (Ca) intake (self-report). Prevalence of VITD insufficiency/deficiency was 84% overall. Participants on no TDF had longer duration of HIV infection and cART, higher viral load, and more advanced Centers for Disease Control and Prevention stage of HIV disease. Those on TDF had lower TRP, higher PTH and CTX; but similar BAP. At week 12, 52% in the VITD group had sufficient VITD, an increase from 17% at baseline, compared to16% at baseline and at week 12 in the PL group (p <0.001 vs VITD). TRP did not change in either group. PTH decreased in the TDF group receiving VITD, but not in the no TDF group receiving VITD or the PL groups. Ca intake affected the strength of the VITD-TDF interaction. CTX and BAP did not change significantly with VITD. There were no clinical bone or renal toxicities or elevations of serum Ca above normal in either group.Conclusions:  Supplementation with VITD3 50,000 IU monthly for 12 weeks in HIV+ youth was safe and reduced VITD insufficiency by 46%. VITD was associated with a significant decrease in PTH in those on TDF-containing cART. There was no change in TRP, CTX, or BAP. The effect of VITD on PTH was seen only in those on TDF, suggesting a possible interaction between TDF, PTH, and VITD.
  • We also calculated the population attributable risk, which accounts for not only the strength of the association of a risk factor with mortality, but also for the prevalence of the condition in the population.We found that having arm muscle in the lowest tertile was associated with a population level risk of 15%. This represents the proportion of deaths over five years in an HIV-infected population that are expected due to having low arm muscle. As an absolute risk, this translates to two deaths per 100 HIV+ ppl expected over five years.For low leg muscle or high VAT, the population level risk was around 7%. This translates to an absolute risk of about 1 death per 100 HIV+ ppts over 5 years.
  • Aging Healthy While Surviving HIV

    1. 1. Beyond Survival-A Breakthrough in Well-Being Nelson Vergel Program for Wellness Restoration Copyright © 2011 by Nelson Vergel
    2. 2. This information (and any accompanying printedmaterial) is not intended to replace the attention oradvice of a physician or other health care professional.Anyone who wishes to embark on any dietary, drug,exercise, or other lifestyle change intended to preventor treat a specific disease or condition should firstconsult with and seek clearance from a qualified healthcare professional.
    3. 3. These Slides Are Available at
    4. 4. AGENDA• Update on lipodystrophy• How to prevent bone loss• Protecting yourself from anal cancer• Exercise: The best therapy• What you did not know about testosterone• Questions?
    5. 5. Glucose metabolism Dyslipidaemia Abnormalities of body composition impairment The changing pattern of clinical spectrum of HIV: LIPODYSTROPHY and Non-infectious Co-MORBIDITIES depict the HIV specific Ageing phenotypes Body image HAND CVD Hepatic steatosis Bone & Kidney disease alterations SexualDepression HT Vit D T2D Cancer
    6. 6. BackgroundInteractions among aging, HIV, and HIV drugs increase the risk of comorbidities. (Vance, Am J Nurs 2010)
    7. 7. Poly-pathology prevalence in cases and controls, stratified by age categories Pp 3.9% 9.0% 20.0% 46.9% Pp 0.5% 1.9% 6.6% 18.7%Pp prevalence was higher in cases than controls in all age strata (all p-values <0.001)Pp prevalence seen cases aged 41-50 was similar to that observed among controlsaged 51-60 controls (p=0.282)
    8. 8. Visceral Fat Reduction
    9. 9. Abdominal Obesity and theCardiometabolic Risk OUTSIDE INSIDE Intra-abdominal or Visceral Fat Waist Circumference Intra-abdominal Fat Intra-abdominal fat is a strong correlate of Cardiometabolic Risk 9
    10. 10. High visceral fat (VAT) increases cardiovascular risk Triglycerides HDL-cholesterol 310 60 248(mg/dl) (mg/dl) 186 45 124 62 30 0 Nonobese Obese Nonobese Obese Low High Low High VAT VAT VAT VAT 10 Pouliot et al. Diabetes. 1992;41:826-834.
    11. 11. DAD Study:Lipodystrophy Incidence 2000-2002 vs 2003-2006 2000-2002 2003-2006
    12. 12. Truvada vs Epzicom Sustiva vs Reyataz+Novir A5224s
    13. 13. A5224s
    14. 14. Researched Options to Decrease Visceral Fat Changing Testosterone HIV Meds? Anabolic Metformin? Steroids? Supplements Egrifta ? Low Carb, High Fiber Weight Loss Diet?Exercise Visceral Liposuction? Fat
    15. 15. Reduction in Abdominal Subcutaneous and VisceralFat In Response to a 7% Exercise-Induced Weightloss, 6 cm reduction in Waist Circumference Visceral Fat Subcutaneous Fat *p< 0.05 vs control MEN WOMEN * *Reduction (%) 30 30 Reduction (%) 20 * 20 * 10 10 0 0 Control Exercise Control Exercise 16Adapted from Ross et al. Ann Intern Med. 2001; Obesity Research. 2004.
    16. 16. DIET Study (Dietary Intervention:Effects on Tryglicerides in HIV Lipodystrophy)Using food records that began from 6 to 24 months beforedevelopment of fat deposition the following factors wereidentified.When compared to people with HIV who developed fatdeposition, patients without fat deposition had:- greater overall energy intakes from their diet (p = 0.03)- greater intakes of total protein (p = 0.01)- more total dietary fiber (p = 0.01)- more soluble dietary fiber (p = 0.01)- insoluble dietary fiber (p = 0.03)- pectin (P = 0.02)Those without fat deposition also were currently doing moreresistance training exercise and were less likely to be smoking -(only borderline statistical significance (p = 0.05))Hendricks at al, Am J Clin Nutr, 2003 Oct;78(4):790-5
    17. 17. Newly FDA Approved Product to Decrease Visceral Fat in HIV+ Patients•2 mg injections under the skin every day. Effectdisappears when stopped•A patient assistance program for those withoutinsurance and incomes under $60K•More information on
    18. 18. Effect of HIV Drugs on LipidsHigher Risk Lower RiskStavudine- D4T Nevirapine- ViramuneAZT Tenofovir- VireadDidanosine-DDI Abacavir- ZiagenLopinavir/r-Kaletra Cholesterol/ Lamivudine- 3TCAmprenavir-Lexiva Emtricitabine- Emtriva Triglycerides Enfurvitide-FuzeonDuranavir-PrezistaSustiva (Atripla) Saquinavir- Invirase Atazanavir- Reyataz Raltegravir- Isentress Maraviroc- Selzentry Etravirine-Intelence DHS/P P
    19. 19. Lipoatrophy Deficits Requiring Correction Temple Fill Cheek Augmentation
    20. 20. HIV Medications and Lipoatropy(Fat Wasting) Low RiskHigher Risk Nevirapine- ViramuneStavudine-D4T Atripla & CompleraAZT Tenofovir-Didanosine-DDI? Lipoatrophy Viread/Truvada Abacavir- Ziagen Fat Wasting Lamivudine- 3TC Emtricitabine- Emtriva Fuzeon Isentress Selzentry All protease inhibitors
    21. 21. Carruthers Lipoatrophy Severity Scale Stage 1 Stage 2 Stage 3 Stage 4James J et al. Dermatol Surg. 2002;28:979-986.
    22. 22. FDA Approved Facial Lipoatrophy Products Off Label Use: Silicone Microdroplet, Artefill
    23. 23. Commonly Used Options for HIV-related Facial Lipoatrophy (From Product Type/Sessions Approved? Cost Sculptra Non- permanent Patient Assistance for Product only (New Fill- 3-7 sessions FDA approved ?_function=name&name=Sculptra Labor cost avg. $500 per session.PolyLactic Acid) needed, the 1 Full price: $1,100 per session for touch up a year product. Radiesse Non- permanent Limited Patient Assistance (Calcium Available hydroxylapitite 2-3+ sessions FDA approved (CaHA) section/Patient-access-program/ needed, then 1 Full Price: $1,200 per session. microspheres) touch up a year Off label use- Permanent FDA approved for Silikon 1000 intraocular No Patient Assistance- Microdroplets 4-8+ sessions injections to treat $700-900 per session needed CMV- related retinal detachment Available in PMMA Permanent Mexico, Brazil and $3,000+ avg. total cost for total other countries.(Polymethyl- 1-2 sessions FDA approved: reconstruction in Mexico:methacrylate ) Artefill but too needed expensive Number of sessions depends on severity of facial lipoatrophy
    24. 24. Proposed Decision Memo for Dermal injectionsfor the treatment of facial lipodystrophysyndrome (FLS) (Jan 2010)“Dermal injections for facial lipodystrophysyndrome are only reasonable and necessaryusing dermal fillers approved by FDA for thispurpose, and then only in HIV infectedbeneficiaries who manifest depressionsecondary to the physical stigmata of HIVtreatment. All other indications arenoncovered.”
    25. 25. Pre- and Post-Silikon 1000 14 treatments over 2 years, 24 cc total
    26. 26. Protecting Your Bones
    27. 27. DEXABONESCAN
    28. 28. Bone Disorders in HIVTreatments for bone loss – Resistance exercise, preventing wasting syndrome, and avoiding tobacco – Calcium (1000- 1500 mg/day) and Vitamin D (400-1000 IU/day ). Get 20 minutes of sun daily – Biophosphonates (Alendronate- Fosamax) – Calcitonin (Intranasal and oral) – Teriparatide (Forteo) – Testosterone and/or thyroid replacement therapy
    29. 29. Bone Drugs Once monthy IV Once a yearSubcutaneous, once daily
    30. 30. NNRTIs? Tenofovir?
    31. 31. Vitamin D Terminology Serum 25-hydroxy vitamin D = 25-OHD Indicator of vitamin D nutritional “status”Vitamin D Status 25-OHD serum concentration ng/mL nmol/LDeficient <12 <30Insufficient 12 to <20 30 to 50Sufficient >20 to 50 >50 to 125Excess >50 >125
    32. 32. Vitamin D Therapy Decreases Parathyroid Hormone (PTH) in Patients Taking Viread (tenofovir) • Randomized trial of Vit D 50,000 IU/wk x 12 weeks vs. placebo in patients on (n=118) or not on (n=85) TDF • Higher baseline PTH levels at baseline in TDF group • Vitamin D had no impact on PTH levels in patients not on TDF Mean Baseline PTH by Vitamin D status and Tenofovir Use PTH Differs by Tenofovir use, not Vitamin D status Changes in PTH on study 52 TDF No TDF 43 35 Day Day Change Change 0 0 27 Vit D 47 -6 26 -2 P=0.001 P<0.001 PBO 37 +2 25 0Havens P, et al. 18th CROI; Boston, MA; February 27-March 2, 2011. Abst. 80.
    33. 33. Human Papiloma Virus (HPV) Related Cancers HPV Infection Incidence of HPV infection increases with sexual exposure Re-infection Associated with persistent risk factors Clearance Common; increases after the age of 40 (as the immune system clears the virus) Reactivation Mainly associated with immunosuppression Persistent Infection Associated with the development of cancer Cancers caused by HPV: Cervical, Vagino/vulvar, Penile, Anal, Oropharyngeal, Squamous cell Higher risk with sero-types: 16, 18, 45 and 56Levine A, et al. 49th ICAAC; San Francisco, CA; Sept. 12-15, 2009; Abst. 400.
    34. 34. Methods to Detect AnalWarts, Cancer, and Dysplasia
    35. 35. Anal Cancer in HIV+ Men and Women Diagnosis and Treatment Pap-smears and simple anoscopy done in the office. Cytology obtained from pap smears. Outpatient under anesthesia: after high resolution anoscopy (HRA) with vinegar, any lesions are treated with infrared coagulation (IRC), which involves inserting a light probe into the anal canal under direct visualization, touching the tip of this light probe to the lesion, and delivering a pre-specified amount of energy. Trained Physicians by UCSF’s anal neoplasia and research group web site :
    36. 36. Signs and Symptoms of Low Testosterone  Loss of muscle mass and strength  Loss of libido and erectile dysfunction  Depression  Lethargy (fatigue, lack of focus)  Bone loss  Some regression of secondary sexual characteristics (body hair loss, etc)  Low or no sperm countTenover JL. Endocrinol Metab Clin North Am. 1998;27:969-987Petak SM, et al. AACE Clinical Practice Guidelines. Available at:
    37. 37. Testosterone and Aging
    38. 38. Testosterone Fractions in the Blood Free T 2% Albumin-bound T 38%T = testosteroneOnly 2% is free Sex Hormone Binding Globulintestosterone SHBG-bound Tand 98% is bound 60%
    39. 39. (binds testosterone)
    40. 40. Testosterone Deficiency(Hypogonadism)• Normal levels in blood: Men... Total test. 300-1100 ng/dL, Free test. 5 - 21 ng/dL Women... Total test. 10-50 ng/dL Free test. 0.10-0.85 ng/dL• Symptoms of testosterone deficiency: Fatigue, low or lack of sex drive, poor appetite, loss of muscle mass & strength, depression
    41. 41. The HPT Hormonal AxisHPT
    42. 42. TestosteroneReplacement Benefits Mental focus Stamina and Bone Strength Sexual function Lean Body Mass
    43. 43. Testosterone Metabolites and Their Functions LH Dehydro Testosterone (DHT) (by 5α-reductase) Androgen Receptor Skin, ProstateTestostero Direct Effect ne Androgen 5-7 Muscle, Brain Receptor mg/day Estradiol (by aromatase) Hair, Brain, Bone Estrogen Oxidation by Liver Receptor Elimination by Kidneys
    44. 44. Testosterone Options Gels BuccalInjections Gels Pellets Patch
    45. 45. Potentially Approved in the Next 12-24 Months
    46. 46. Side Effect: Gynecomastia (breast enlargement in men)Treatment: Estrogen Blocker Medications or surgery (in worst cases)
    47. 47. Side Effect: Increased number of red blood cells (polycythemia) Watch out for hematocrit over 52 !Solution: Donate bloodor therapeutic phlebotomy (4-5 units every 3-4 months)
    48. 48. Side Effect: Testicular Shrinkage (atrophy)Treatment:Human Chorionic Gonadotropin(hCG)
    49. 49. Side Effect : Increased prostate size (benign prostatic hypertrophy)Prevention:Digital Rectal Exam (DRE)Prostatic Specific Antigen (PSA) blood test
    50. 50. For More
    51. 51. Exercise, the Best Therapy for Most Health Problems
    52. 52. Low Arm Muscle is associated withhighest population-level mortality riskin multivariable analysis 20% Population Attributable Risk 15.1% 15% 10% 7.2% 6.5% 5% 0% Arm SM Leg SM VAT Tertile 3 Tertile 1 Tertile 1 Tertile of Skeletal Muscle or Adipose Tissue
    53. 53. Exercise: The Best Medicine Benefits: total and abdominal fat improves insulin sensitivity improves glucose tolerance increases HDL cholesterol triglycerides and LDL increases muscle mass improves endurance improves strength improves bone density improves mood decreases frailty
    55. 55. Aerobic (Cardiovascular) Exercise Start with a brisk walk every day if tired Concentrate in low impact or no impact exercises (e.g. Elliptical Trainers) Do what you enjoy (bicycling, roller skating, etc) Good for burning fat, triglycerides, blood sugar, but it may decrease muscle mass 20 - 30 minutes 3-4 times a week is enough for many people Cardiovascular exercise may increase fat loss under the skin
    56. 56. Progressive Resistance Exercise (PRE) Warm up and stretch before a session Start with compounded exercises Lift maximum weight for muscular failure (exhaustion) at 8-12 repetitions One body part per week One hour sessions 3-4 times a week One light set and two heavier sets per body part If no access to a gym, start with crunches, push ups, and squats at home. Use stairs! For more details, visit
    57. 57. Best Exercise Sites with videos, etc www.MyFit.caIpod exercise routine downloads:
    58. 58. For More Information More details in “Built To Survive” and ”Testosterone- A Man’s Guide” ( or Email:Nelson Vergel – Websites: Join my Internet discussion group by sending a blank email to
    59. 59. Questions?