DIVISION OF DIVISION OF DISEASE DISEASE

PREVENTION PREVENTION Director

Principal Investigator

G Shor-Posner, PhD

WORKSHOP COORDINATORR. DIAZ

SR. STAFF ASSOCIATE(Fogarty/Massage)

FOGARTY ADMINISTRATORP. O’DONOGHUE

RESEARCH COORDINATORN. QUINTERO

RESEARCH ASSOCIATE(Fogarty/Massage)

EDUCATIONJ. LEWIS, PhD

(Fogarty/Massage)

Family Medicine

INTERNATIONALT. BREWER, MD

(Fogarty/Massage)

CAP

FOGARTY TRAINEES

BrazilColombia

Dominican RepublicJamaica

Peru

LABORATORY VOLUNTEER

A. Posner, PhD

CONSULTANTSG. Moreno-Black,

PhDG. Zhang, MD

Eating Disorders – Eating Disorders – Anorexia, Bulimia, Anorexia, Bulimia, ObesityObesity

SLIM Disease

Role of Role of MicronutrientsMicronutrients

Immune Processes

Antioxidant Defense

Brain Function

Prevalence of Prevalence of SpecificSpecific

Nutrient DeficienciesNutrient DeficienciesHIV-1 INFECTED

HOMOSEXUAL MEN

DRUG USERS

PEDIATRIC

PATIENTSVITAMIN A 10% 55% N/AVITAMIN B6 30% 15% 7%VITAMIN B12 12% 8% 11%VITAMIN E 18% 47% N/AZINC 26% 49% 71%SELENIUM 11% 7% 33%

Beach et al. AIDS 1992;6:701.Baum et al. IX Intl Conf AIDS, Berlin, 1994;1020.Bologna et al. J Nutr Immun 1994;3:41-48.

COBALAMIN STATUS & BRAIN FUNCTION

• NEUROLOGICAL COMPLICATIONSSubacute degeneration of the spinal cord, optic nerves, cerebral white matter, and peripheral nerves

• PSYCHOLOGICAL SYMPTOMSApathy, irritability, depression, confusion, dementia

MICRONUTRIENT ANTIOXIDANT PROTECTIONSCAVENGERSSCAVENGERS-tocopherol, ascorbic acid, -tocopherol, ascorbic acid, --carotenecarotene

ENZYME DEFENSE SYSTEMSENZYME DEFENSE SYSTEMSSelenium, Zinc, Copper, Selenium, Zinc, Copper, Manganese, IronManganese, Iron

Specific Nutritional Specific Nutritional Deficiency and HIV-Related Deficiency and HIV-Related

MortalityMortalityNUTRITIONALDEFICIENCY

RISK RATIO(95% C.I.) P-VALUE

Prealbumin 4.01 (1.46-11.0) 0.007

Vitamin A 3.23 (1.10-9.48) 0.03

Vitamin B6 2.35 (0.74-7.43) 0.14

Vitamin B12 8.33 (1.69-41.1) 0.009

Vitamin E 0.44 (0.15-1.30) 0.14

Zinc 2.91 (1.04-8.18) 0.04

Selenium 19.9 (5.52-71.9) <0.0001

Baum et al. JAIDS 1997.

e

Essential Trace Element

Immune Function

Antioxidant - Se-GPx

Neuroprotection

SeleniuSeleniumm

Selenium Therapy Selenium Therapy TrialTrial

• 259 HIV+ Drug Users

• 200 g/day Selenium

OR Placebo

NIDA

Selenium Therapy Trial Selenium Therapy Trial FindingsFindings

Quality of life (health)

Se-Treated vs. Placebo

Mycobacterial infectionsHospitalizationsAnxiety

Shor-Posner et al. JAIDS 2002.

NIDA

Selenium Neuroprotection Selenium Neuroprotection TrialTrial

115 HIV+ Drug Users115 HIV+ Drug Users

200 200 g/day Seleniumg/day Selenium

OR PlaceboOR Placebo

One YearOne Year

Findings from the Selenium Trial

0

20

40

60

80

100

S P S P S P S PS P S P S P S P BaselineBaseline One YearOne Year BaselineBaseline One YearOne Year State Anxiety Trait AnxietyState Anxiety Trait Anxiety >35 >35>35 >35

**

Shor-Posner et al. Intl J Psychiatr in Med 2003.

Gr o

up

Gr o

up

%%

ARVARV

HIV Wasting in the HAART HIV Wasting in the HAART EraEra

Lipodystrophy – HIV-Related Adipose Redistribution

FAT LOSS LimbsButtocksFace

HIV Wasting in the HAART HIV Wasting in the HAART EraEra

Lipodystrophy – HIV-Related Adipose RedistributionFAT ACCUMULATION Waist

BreastsFace (Neck)

INTERSCAPULAR FAT PAD - “Buffalo Hump”

Nutrition in the HAART EraNutrition in the HAART EraPharmacotherapy ChallengesPharmacotherapy Challenges

1.Potential Interactions with Food

2.Body Metabolism3.Side Effects

HIV/AIDSERA OF ERA OF HAARTHAART

55%55%

Coleburdaset et al. Intl J STD & AIDS 2003;14:672-4.Coleburdaset et al. Intl J STD & AIDS 2003;14:672-4.deVisser & Grierson. AIDS Care 2002;14:599-606deVisser & Grierson. AIDS Care 2002;14:599-606Hsiad et al. JAIDS 2003;33:157-165.Hsiad et al. JAIDS 2003;33:157-165.

CAM CAM USEUSE

NCCAM MAJOR TYPES OF CAM

• ALTERNATIVE MEDICAL SYSTEMS•Homeopathic Medicine, Ayurveda

• MIND-BODY INTERVENTIONS•Prayer, Meditation, Art, Dance, Music

• BIOLOGICALLY BASED THERAPIES•Herbs, Foods, Vitamins

• MANIPULATIVE & BODY-BASED METHODS

•Massage, Chiropractic

• ENERGY THERAPIES•Reiki, Magnetic Fields

MAJOR TYPES OF CAM, cont…

REASONS FOR CAM USE IN HIV/AIDS

HIV-Related Problems• Nausea, Depression, Insomnia, Weakness

Sparger et al. J Altern Complement Med 2000;6:415-Sparger et al. J Altern Complement Med 2000;6:415-22.22.

Still NO Cure, NO VaccineStill NO Cure, NO Vaccine

•Regain Sense of ControlRegain Sense of Control

EnergyEnergy

•Maintain Well-BeingMaintain Well-Being

Side effects of ARV drugsSide effects of ARV drugs

REASONS FOR CAM USE IN HIV/AIDS

UMIAMI – Touch Research Institute UMIAMI – Touch Research Institute (1992)(1992)

First Center in the world devoted solely to the First Center in the world devoted solely to the study of touch and its application in science and study of touch and its application in science and

medicine medicine

MASSAGE

Universal InstinctUniversal Instinct Touch is beneficialTouch is beneficial

Touch – integral part of primate Touch – integral part of primate social systemsocial system

TRI MASSAGE STUDIES IN HIVGay Men (n=29, 20 HIV+, 9 HIV-)1

Massage vs Within-Subjects Control Group(daily for 1 month)

NK cell numberNK cell cytotoxicitySoluble CD8

No changes in CD4, -2, NeopterinIronson et al. Intern J Neurosci 1996;84;205-Ironson et al. Intern J Neurosci 1996;84;205-17.17.

TRI MASSAGE STUDIES IN HIV

HIV in Adolescents (n=24)1

Massage vs Muscle Relaxation(2x/week for 12 weeks)

NK cell number (CD56)CD4/CD8 RatioCD4 Number

Diego et al. Int J Neurosci 2001;106:35-Diego et al. Int J Neurosci 2001;106:35-45.45.

MASSAGE AND HIV+ CHILDREN

NO studies in young children

NCCAM – “Massage to Enhance Well-Being in HIV+ Dominican Children”

STUDY DESIGN – Clinical Trial

• Consented, HIV+ Children (n=54)• Ages 2-8 yrs.• Randomized

• Massage• 2x/week, 20 minutes for 12 weeks

• Friendly Visit (Reading/Drawing)• 2x/week for 12 weeks

CENISMI – Robert Reid Cabral Children’s Hospital

STUDY OUTCOMES

ACCEPTANACCEPTAN

CECE

COMPLIANCECOMPLIANCE

IMMUNE FUNCTIONIMMUNE FUNCTION DEVELOPMENTDEVELOPMENT

IMMUNE PARAMETERS –

PRE-POST INTERVENTION

VariableVariable MASSAGEMASSAGE(n=10)(n=10)

CONTROLCONTROL(n=14)(n=14) p-value*p-value*

Baseline CD4 Baseline CD4 (Mean(Mean±SD)±SD)Final CD4Final CD4ChangeChange

802±423852±438

+ 50±163

885±535696±453

- 189±331 0.03

Baseline CD8 Baseline CD8 (Mean(Mean±SD)±SD)Final CD8Final CD8ChangeChange

1440±5661820±984

+ 380±593

2722±17122546±1509

- 176±646

0.03

0.04

Baseline CD3 Baseline CD3 (Mean(Mean±SD)±SD)Final CD3Final CD3ChangeChange

2437±7112921±1364

+ 484±901

4003±21333655±1852

- 348±938

0.02

0.04

FINDINGS

Relative risk of having >20% decrease in CD4 cell count higher in controls. (RR=5.7, p=0.03)

Mean CD4 Cell CountMean CD4 Cell Count MassageMassage ControlsControls

NIH/NCCAM 1RO1 AT02689NIH/NCCAM 1RO1 AT02689Title:Title: Massage Benefits in HIV+ Children: Mechanisms Massage Benefits in HIV+ Children: Mechanisms of Actionof Action

Fogarty International Training Fogarty International Training ProgramProgram

HIV/AIDS and TBHIV/AIDS and TB

1988 - 1988 - 20092009

1913-19671913-1967““because disease knows no boundaries – and because disease knows no boundaries – and “because we care”.“because we care”.

PROGRAM OBJECTIVESPROGRAM OBJECTIVES Develop scientific and Develop scientific and

technical technical infrastructuresinfrastructures

Train cadre of Train cadre of scientists who can:scientists who can: Guide their countries in Guide their countries in

developing HIV/AIDS developing HIV/AIDS programs;programs;

Implement interventions Implement interventions to reduce the burden of to reduce the burden of disease.disease.

MILESTONESMILESTONES

• Training: 280 scholars Training: 280 scholars from 26 different from 26 different countries in Latin countries in Latin America and Caribbean;America and Caribbean;

• Development of Development of effective scientific effective scientific infrastructures for infrastructures for biomedical research in biomedical research in Brazil, Colombia, the Brazil, Colombia, the Dominican Republic Dominican Republic and Peru.and Peru.

CHALLENGES OFCHALLENGES OF INTERNATIONAL INTERNATIONAL

RESEARCHRESEARCHHIV/AIDS IN LATIN AMERICAHIV/AIDS IN LATIN AMERICA

Highly Highly DiverseDiverse Parallel Epidemic of Parallel Epidemic of

TBTBAccess to Access to CareCare

Stigma and Stigma and DiscriminationDiscriminationARTART

ChallengesChallenges• Parenting (PMTCT-PLUS)Parenting (PMTCT-PLUS)• Optimal feeding practicesOptimal feeding practices• Coping with HIVCoping with HIV

Do not stop with Do not stop with childbirthchildbirth

THE NEEDS OF MOTHERSTHE NEEDS OF MOTHERS

OPTIMAL TREATMENT AND OPTIMAL TREATMENT AND MANAGEMENT OF HIV/AIDSMANAGEMENT OF HIV/AIDS

**ACCESSACCESS**ADHERENCEADHERENCE**EFFECTIVENESSEFFECTIVENESS

ANTIRETROVIRAL ANTIRETROVIRAL THERAPIES THERAPIES

MILESTONESMILESTONES

Achievements of independent research funding by Achievements of independent research funding by Trainees:Trainees:

Global FundGlobal Fund

NIH / CIPRA / GRIPNIH / CIPRA / GRIP

World BankWorld Bank

Elizabeth GlaserElizabeth Glaser

UNICEFUNICEF

CARECCAREC

• Dr. R DeSouzaDr. R DeSouza

• Dr. J SampaioDr. J Sampaio

• Dr. G MalaquiasDr. G Malaquias

• C BisolC Bisol

• Dr. B AcostaDr. B Acosta

• Dr. X BurbanoDr. X Burbano

• Dr. J GalindoDr. J Galindo

• Dr. AM Granada-CopeteDr. AM Granada-Copete

• Dr. H RinconDr. H Rincon

J. BAEZ, M.D.J. BAEZ, M.D.R. CASTILLO, M.S.R. CASTILLO, M.S.

W. DUKE, M.D.W. DUKE, M.D.R. MENDOZA, M.S.R. MENDOZA, M.S.

M. MIRIC, M.S.M. MIRIC, M.S.E. PEREZ-THEN, M.D.E. PEREZ-THEN, M.D.

N. SALCEDON. SALCEDOS. SOTO, M.D.S. SOTO, M.D.

Treatment StrategiesTreatment StrategiesPMTCT – Adherence; Stigma ReductionPMTCT – Adherence; Stigma Reduction

Fogarty Fogarty HIV/AIDS HIV/AIDS WorkshoWorkshopsps

CLINICAL CLINICAL A.G. HOLLEY HOSPITAL, A.G. HOLLEY HOSPITAL, LANTANA, FL LANTANA, FL

WORKSHOP“Meeting the Challenges of Research and Interventions for HIV/AIDS in International

Venues”