Post on 13-Dec-2015
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
:i
;
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
w
h: *S&kdGlBrutrdffi,
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
,,: ,, r,- ;;rrJli I , :1 . ,,r S,:.ir
I
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
roo
i Antiretroviral Activity -i Historical Perspective: l8l: ln tgga: ls7:
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Active Anti-Therapy
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
to
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.