PEDIATRIC HIV

Dominicus Husada

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HISTORY
1981

r
r

lGposiS sarcoma reoottd in 8 vouno oav

'
hoinoser<ual men (NY, San RantiscoJ
The disece was orioinallv tenrcd GavRelated Immune DeficienLy (GRID)

1982

ln December, CDC reported the first cases

of possible niother to'child Bansmission of
AIDS

HISTORY
1983

In May 1983, Dr. Luc Montagnier, attfie

Instihjte Pasteur in France reported the
isolation of a new virus (beliwed was the
cause of AIDS) named lymphadenopathyassociated virus or l-AV

a sample of IAV was sent to the National

Cancer Instifirte, Dr. Robert Gallo.

HISTORY
1984

Dr. Robert Gallo isolated the virus which

caused AIDS, and narned Human T<ell
lymphotropic virus type III or HTLV-III,

ituilishdon 4l,lay')

But LAV and HTLV-III

rarcre

the same virus,

2008

r
r

Dr. Gallo admitted this fraud in 2007-2008

The Nobel Prize was awarded fior Dr. Luc
Montagnier..--

AND SO MANY FAMOUS PEOPLE

BECAME THE VICTIMS SINCE

. FIRST PEDIATRIC
; PATIENTS
: r In the world : USA 1982 ( Mother to

CniU Transmission = MTCT )

In Thailand : late 80s
In Dr. Soetomo Hospital :

i
i

E,2.5 y o, hospltalizd2O January

ir
ir

i
:
i
;

2000, died after 28 days in the ward

EPIDEMIOLOGY - WORLD

. Pdople living with

HIV

33 million [30

36 mln]

Niw HM infections

2.7 million [1.6

3.9 mln]

2.0 million [1.8

2.3 mln]

. Diaths due lo AIDS

6UNA!-D-57r;

iNEW HIV INFECTION PER DAY

h:

*S&kdGlBrutrdffi,

ESTIMATED NUMBER IN

INDONESIA

EPTDEMIOLOGY -

INDONESIA
r Indonesia (2008) : 4h fastest
country in the world in increasing
number of patients
r East Java Juni 2011: 3775 rank
4ut in Indonesia ( after Jakafta,
Papua, and West Java )

EPIDEMIOLOGYDr. SOETOMO HOSPITAL 2013

: childr"r *rh
r

*r-"d

H^,
untiltoday : >100
Died or Lost of Follow Up : > 100

PATHOBIOLOGY ETIOLOGY
PATHOGENESIS
PATHOPHYSIOLOGY

THE VIRUS

- HIV 1

RETROVIRIDAE
grl!0-..'EHT

b,xl.c!
tffi
tlt hl47!t

gag

Hn'-ntiA

THE VIRUS
r Refovirus, Lentivirus genus
r Entered human population in Africa 70 years
490
r HIV 2 = less pathogenic relative

r
r

10 clades ( sufipes )
Some importart proteins

- pL6, p24, /9, F

- Protcasc, Rdersc Trarccrlptaic,
- 9p120,9p41
- Tat, Rcf, Vtf, Vpu,

Vpr, Ncf

Intg.asc

AND THE IMMUNITY

KEY PLAYERS
r

T-cell with Olue)

HIV virions

r T-cells (round)
intencUng with DC

DendriUc cell

IM MU NO1OGIC ABNORJvIALTTIES

ASSOCIATEDWITH HIV-1
INFECTION
Cellular
Decreased delayed type hypersensitivity skin
rcaction
T-lymphocytes
NK cells

r
r
r
r
r

APC

Phagocytes ( rnonocytes, PMN )

Humoral
B.lymphocytes
Spccific anubody responss

r
r
r

Cybhnes

TRANSMISSION

r
r

Blood Transfusion

Sexual Intercourse

Unknown

Drug Users

Estimated Risk and Timing of

iUother-To-Child (MTCT) HfV Transmission

6-24 montlr

12%

8%

sorce:

De cock KM, et al JAMA. zffi; 283 (9): I175-82

Konis et al. JAMA 20OI; DeCock et al. JAMA 2OOO

WHE]I YOU HAVE CLOSE COTITACTS

wrTH THE PATTEI{TS, THESE

ACTIOI{SARE SAFE

Shake hand

r'Hug

r
r
r
r

Eating with the same equipments

Using toilet simultaneously
Through insect bites
Tidak pemah ada laporan orang tertular
karena 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 )

Infant / Child

- History of the parents

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

CLINICAL CONDITION OF
THE CHILD .I'T'rt
.
.
.
.
r

Persistcnt diafihea

Pcrsistert

fser

Malnuuiti,on
Generalized Lyrnphadenopathy

OpportrnisUc Infections

-TB

- Fungal infecbon
- Human Herpes Virus
- Tuoplascb

- cmr'
-

Pneumonia

,,: ,, r,- ;;rrJli I ,

:1

,,r

S,:.ir

i DEFINITE DIAGNOSIS
r Age > 18 months

;r

j
I

: antibody test ( 2 or
3 methods )
Age < 18 months : PCR, p24 antigen,
."n"* ( 2 positive results )

CLINICAL
CLASSIFICATIONS
r

Based on 2 Main Sources

-WHO Guideline
-CDC Guideline

New version of these guidelines

available

OPPORTUNISTIC
INFECTIONS
r

Infections happened mainly because

of immunodeficiency state

Often cause no harm for

immunocompetent children
This is the killer !!!

Treat as best as you c;etn, bebre

starting the Anti Retro-Viral drug

OPPORTUNISTIC
INFECTIONS
r Tuberculosis

r rcP ( pneumoclstic jiroveci pneumonia )

r CMV and other Human Herpes Virus
r

Toxoplamosis

r HA/ ( human papilloma virus )

r Cryptosporidium Parvum, Isospora Belli,
mrcro and macrospora
r cryptococcus Neoformans
r Penicillium Mamefei. Histoolasma
Capsulatum, Aspergillus Fbvus

TREATMENT CRTTERIA
GUIDELINES:
r WHO 2008

WHO 2010

r CDC 20O8
r BHWA 2008
r PENTA 2(D8
BASED ON :

Clinical condition, immunolggy, virolggv

TREATMENT CRTTERIA
GUIDEUNES INDONEIA:

Departemen Kesehatan 2008 ( based on

wHo

2006 )

Kementerian Kesehatan 2012 (in press)

Need to be revised

THE DRUGS. CLASSES

r Anti Retro Viral ( ARV ) : 6 Classes
r Single and Fixed Drug
Combinations

Non ARV

- Cotrimoxazole, macrolides,
-Antifungal, antiviral
-Anti-lipid

w Antiretroviral

roo

Antiretroviral Activity -

Historical Perspective

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Active AntiTherapy
Adv.ntages
- Gffectivs
- morbldllV I and rprtality J
- chronic dlseasc
- Hry+ chlldren gt pregnant
drernselves
Disadvantages
- to)dctty / advcrsc cvcnts
- compllance / poor

antiretroviral drugs
tor chlldren

3 main classs
NRTI: take nucleoslde

analogues
NNRTI: binds to reverae

lranscrlptase
Pl: binds competltlve

to

CURRENT ARV MEDICATIONS

r ARV is never an ernergency

r Prepare the patient carefully bebre
start ARV
Look br OI

r
r Avoid IRIS
r Prepare the caregivers
r Don't start if doubtful

counseling

r Life-long
: r Regular visit every 2-3 months
i 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 )
Male Circunrcision, etc.

r
r ABC ( Abstinence -

Be Faithful

Condoms )

r TREATIIENT IS PREVENTION !!!

PREVENTIONS. PMTCT
r Opt in vs opt out : Thai and

r
r

Malaysia o<periences
Cannot be much lower than
Free milk for babies

1olo

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 deadly

ser'rous disease

r Ifs look like diabetes, hypertension,

r

hypercholesterolemia, and so on
Treatment as prevention
Another "cuted" paUent ? ( Remember
Timothy Brown and Mississippy Baby )

THE CURE
r

Since 2011 people spoke about

cure (Vancouver Meeting)
r Only 3 curable patients in history
- all were published in NEIM
r The first was questionable : NEIM
March 30, 1995 (

THE BERLIN PATIENT

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

Hematopoetic stem cell transplant from

a donor with the CCR5 delta 32

mutation

r Two transplants ftom

1 donor at 2007
and 2008
No
In 2009, after 1 year off drugs
HW found, in all over the body

THE MISSISSIPPI BABY

r Very early and very high dose
in the newborn may alter the
establishment and long term
persistence of HIV-I infection
r Other studies follow

ARV

THE FUTURE
r One important message : cure
possible !!!

is

THE FUTURE
r

At this moment we

dont give any beatmentto

)ourdaughter. When the situdim gtting

vvorse we will treat her immediably. We now

have some very good drugs and I can piomise

you that she will be okay with those drugs for
at least zl0 years theoretically.

In the fub.rre I believe she will be able to tell

story to her son and daughter, '1 used to have
HW'. 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 pcdiatrlc

HIV care. Cambridgc Universlty Prcss. Cambridgc,

WHO casc definitions of HIV for surveillance and

revlscd clinical staoino and lmmunolooical
classlficaUon of Hl!-rElated disease iri'adults and

r
r
r

zn7.

children. 2fi)7
WHO guideline for the use of ARV in pediabic HW
infection. 2010.
CDC Guldcllnc : Rslsd classncauon systam for
HIV infectjon in childrcn less than 13 yiars. 1gS+.
CDC guidelinc for thc use of ARV in pediatic Hry

indon.2008.