PEDIATRIC HIV

Dominicus Husada

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HISTORY

1981r lGposiS sarcoma reoott€d in 8 vouno oav

hoinoser<ual men (NY, San RantiscoJ - 'r The disece was orioinallv tenrcd Gav-

Related Immune DeficienLy (GRID)

1982r ln December, CDC reported the first cases

of possible niother to'child Bansmission ofAIDS

HISTORY

1983

r In May 1983, Dr. Luc Montagnier, attfieInstihjte Pasteur in France reported theisolation of a new virus (beliwed was thecause of AIDS) named lymphadenopathy-associated virus or l-AV

r a sample of IAV was sent to the NationalCancer Instifirte, Dr. Robert Gallo.

HISTORY

1984r Dr. Robert Gallo isolated the virus which

caused AIDS, and narned Human T<elllymphotropic virus type III or HTLV-III, fituilishdon 4l,lay')

r But LAV and HTLV-III rarcre the same virus,

2008r Dr. Gallo admitted this fraud in 2007-2008r The Nobel Prize was awarded fior Dr. Luc

Montagnier..--

AND SO MANY FAMOUS PEOPLEBECAME THE VICTIMS SINCE

. FIRST PEDIATRIC; PATIENTS

: r In the world : USA 1982 ( Mother toi CniU Transmission = MTCT )i

i r In Thailand : late 80si r In Dr. Soetomo Hospital :

i E,2.5 y o, hospltalizd2O Januaryi 2000, died after 28 days in the wardi

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EPIDEMIOLOGY - WORLD

. Pdople living with HIVi

. N€iw HM infections:

. Diaths due lo AIDS

33 million [30 - 36 mln]

2.7 million [1.6 - 3.9 mln]

2.0 million [1.8 - 2.3 mln]

6UNA!-D-57r;

iNEW HIV INFECTION PER DAY

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ESTIMATED NUMBER ININDONESIA

EPTDEMIOLOGY -INDONESIA

r Indonesia (2008) : 4h fastestcountry in the world in increasingnumber of patients

r East Java Juni 2011: 3775 ) rank4ut in Indonesia ( after Jakafta,Papua, and West Java )

EPIDEMIOLOGY-Dr. SOETOMO HOSPITAL 2013

: childr"r *rh H^, *r-"duntiltoday : >100

r Died or Lost of Follow Up : > 100

PATHOBIOLOGY -ETIOLOGY

PATHOGENESIS

PATHOPHYSIOLOGY

THE VIRUS - HIV 1RETROVIRIDAE

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THE VIRUS

r Refovirus, Lentivirus genusr Entered human population in Africa 70 years

490r HIV 2 = less pathogenic relativer 10 clades ( sufipes )r Some importart proteins :

- pL6, p24, /9, F- Protcasc, Rdersc Trarccrlptaic, Int€g.asc- 9p120,9p41- Tat, Rcf, Vtf, Vpu, Vpr, Ncf

AND THE IMMUNITY -KEY PLAYERS

r T-cell with Olue)HIV virions

r T-cells (round)intencUng with DC

r DendriUc cell

IM MU NO1OGIC ABNORJvIALTTIESASSOCIATEDWITH HIV-1INFECTIONCellularr Decreased delayed type hypersensitivity skin

rcactionr T-lymphocytesr NK cellsr APCr Phagocytes ( rnonocytes, PMN )Humoralr B.lymphocytesr Spccific anubody respons€sr Cybhnes

TRANSMISSION

r Blood Transfusion

r Drug Users

r Sexual Intercourser Unknown

Estimated Risk and Timing ofiUother-To-Child (MTCT) HfV Transmission

6-24 montlr

12% 8%

sorce: De cock KM, et al JAMA. zffi; 283 (9): I175-82Konis et al. JAMA 20OI; DeCock et al. JAMA 2OOO

WHE]I YOU HAVE CLOSE COTITACTSwrTH THE PATTEI{TS, THESEACTIOI{SARE SAFE

r Shake handr'Hugr Eating with the same equipmentsr Using toilet simultaneouslyr Through insect bites

r Tidak pemah ada laporan orang tertularkarena berciuman

CLINICAL COURSE

r 3 types :

- Rapid progressor

-Slow progressor

-Long term non progressor

- Hlstory of tfic motrer / httrer ( lDt , CS.Vlr, ctc )- Cllnkal condiUon ofthe mother (TB, ctc )

r Infant / Child :

- History of the parents

- Cllnical condition of thc parcnts- Clinical condition of thc chlld- Labontory results ( CBC, lmmunology, vlrology )

CLINICAL CONDITION OFTHE CHILD .I'T'rt. Persistcnt diafihea. Pcrsistert fser. Malnuuiti,on. Generalized Lyrnphadenopathyr OpportrnisUc Infections :

-TB- Fungal infecbon

- Human Herpes Virus

- Tuoplascb- cmr'- Pneumonia

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i DEFINITE DIAGNOSIS

r Age > 18 months : antibody test ( 2 or3 methods )

; r Age < 18 months : PCR, p24 antigen,

j ."n"* ( 2 positive results )

I

CLINICALCLASSIFICATIONS

r Based on 2 Main Sources :

-WHO Guideline

-CDC Guideline

r New version of these guidelinesavailable

OPPORTUNISTICINFECTIONSr Infections happened mainly because

of immunodeficiency stater Often cause no harm for

immunocompetent childrenr This is the killer !!!: Treat as best as you c;etn, bebre

starting the Anti Retro-Viral drug

OPPORTUNISTICINFECTIONSr Tuberculosisr rcP ( pneumoclstic jiroveci pneumonia )r CMV and other Human Herpes Virusr Toxoplamosisr HA/ ( human papilloma virus )r Cryptosporidium Parvum, Isospora Belli,

mrcro and macrosporar cryptococcus Neoformansr Penicillium Mamefei. Histoolasma

Capsulatum, Aspergillus Fbvus

TREATMENT CRTTERIA

GUIDELINES:r WHO 2008 t WHO 2010

r CDC 20O8

r BHWA 2008

r PENTA 2(D8

BASED ON :

r Clinical condition, immunolggy, virolggv

TREATMENT CRTTERIA

GUIDEUNES INDONEIA:

r Departemen Kesehatan 2008 ( based onwHo 2006 )

r Kementerian Kesehatan 2012 (in press)

r Need to be revised

THE DRUGS. CLASSES

r Anti Retro Viral ( ARV ) : 6 Classes

r Single and Fixed DrugCombinations

r Non ARV :

- Cotrimoxazole, macrolides,

-Antifungal, antiviral

-Anti-lipid

w Antiretroviral

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Adv.ntages- Gffectivs- morbldllV I and rprtality J- chronic dlseasc- Hry+ chlldren g€t pregnant

drernselvesDisadvantages- to)dctty / advcrsc cvcnts- compllance / poor

antiretroviral drugstor chlldren

3 main class€sNRTI: take nucleoslde

analoguesNNRTI: binds to reverae

lranscrlptasePl: binds competltlve

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CURRENT ARV MEDICATIONS

r ARV is never an ernergencyr Prepare the patient carefully bebre

start ARV

r Look br OIr Avoid IRISr Prepare the caregivers ) counselingr Don't start if doubtful

r Life-long: r Regular visit every 2-3 monthsi r 24 hour access ( physician, clinical: nurse specialists, other profesionals )i r Meetings : pre / post treatment,i multidisciplinaryteam

PREVENTIONS

I vaccine

r PMTCT ( Prwention of Mother to Child

Transmission )r Male Circunrcision, etc.

r ABC ( Abstinence - Be Faithful -Condoms )

r TREATIIENT IS PREVENTION !!!

PREVENTIONS. PMTCT

r Opt in vs opt out : Thai andMalaysia o<periences

r Cannot be much lower than 1olo

r Free milk for babies

ADOLESCENT

r Most complicated group

r'There are more life than drugs'r Special needs ( doctor, PrivacY,

etc )

THE FUTURE

r No longer considerd as a deadlyser'rous disease

r Ifs look like diabetes, hypertension,hypercholesterolemia, and so on

r Treatment as prevention

r Another "cuted" paUent ? ( RememberTimothy Brown and Mississippy Baby )

THE CURE

r Since 2011 people spoke aboutcure (Vancouver Meeting)

r Only 3 curable patients in history- all were published in NEIM

r The first was questionable : NEIMMarch 30, 1995 (

THE BERLIN PATIENT

r llmothy Ray Brown (US& live in Berlin)r AIDS and AML

r Hematopoetic stem cell transplant froma donor with the CCR5 delta 32mutation

r Two transplants ftom 1 donor at 2007and 2008

r In 2009, after 1 year off drugs ) NoHW found, in all over the body

THE MISSISSIPPI BABY

r Very early and very high dose ARVin the newborn may alter theestablishment and long termpersistence of HIV-I infection

r Other studies follow

THE FUTURE

r One important message : cure ispossible !!!

THE FUTURE

r At this moment we dont give any beatmentto)ourdaughter. When the situdim g€ttingvvorse we will treat her immediably. We nowhave some very good drugs and I can piomiseyou that she will be okay with those drugs forat least zl0 years theoretically.

r In the fub.rre I believe she will be able to tellstory to her son and daughter, '1 used to haveHW'. Well, it will not be in the ne)(t 5 years,but it is certainty not bo far away.

Sam Waltes( SL MtVs Hcpttal )

FURTHER READINGS

r Zcichncr Sl- Rcad JS, eds. Textbook of pcdiatrlcHIV care. Cambridgc Universlty Prcss. Cambridgc,zn7.

. WHO casc definitions of HIV for surveillance andrevlscd clinical staoino and lmmunolooicalclasslficaUon of Hl!-rElated disease iri'adults andchildren. 2fi)7

r WHO guideline for the use of ARV in pediabic HWinfection. 2010.

r CDC Guldcllnc : Rsls€d classncauon systam forHIV infectjon in childrcn less than 13 yiars. 1gS+.

r CDC guidelinc for thc use of ARV in pediatic Hryindon.2008.