PAEDIATRIC AIDS

DR. Ayam R.Kalingonji

OBJECTIVES
EPIDEMIOLOGY AND PATHOGENESIS OF PAIDS
MODES OF MTCT
STRATEGIES FOR PMTCT
CLINICAL CASE DEFINITION OF PAIDS
HANDLING HIV EXPOSED CHILDREN
CLINICAL PRESENTATION,COMPLICATIONS AND
PROGNOSTIC INDICATORS
MANAGEMENT OF PAIDS

)
EPIDEMIOLOGY
HIV/AIDS is a major cause of infant and childhood
mortality and morbidity in Africa

AIDS accounts 7.7% mortality in children under five in

Africa

Most of them (95%)acquire infection from their

mothers during pregnancy, labor and delivery or after
birth during breastfeeding(vertical transmission)
The epidemiology of HIV and AIDS:
The prevalence of PAIDS is a direct reflection of the
prevalence of HIV infection in women of child bearing
age.
In sub-Saharan Africa , women represented 57% of all
people living with HIV/AIDS.
In Eastern and Southern Africa the prevalence of HIV
infection among pregnant women ranges from 6–40%
in most countries though in some regions in South
Africa prevalence rates exceed 50%.
HIV prevalence in TZ
Scaling-up access to
antiretroviral treatment
has helped Tanzania
minimise the impact of the
epidemic
As a result, between 2010
and 2015, the number of
new infections declined by
more than 20% and the
number of people dying
from an AIDS-related
illness halved
HIV prevalence for women was 6.2%, compared to
3.8% for men.

Nearly a fifth of all new HIV infections in Tanzania are

due to mother-to-child transmission (MTCT)

HIV prevalence among pregnant women is 6.8%

Etiology of HIV
In TZ, HIV infection is caused by the HIV – 1 subtype.

No infection with HIV – 2 has been reported yet.

The common HIV – 1 subtype in Tz are: A, C, D and

their recombinants
Modes of transmission;
There are three main modes of transmission;
MTCT or vertical transmission
Contact with infected blood or blood products
Sexual contact or horizontal transmission.
More than 90% of Paediatric HIV infections are acquired
through mother to child route.
The absolute risk of transmission
without any intervention is btn
• 5-10% during pregnancy
•10-15% during labour and delivery,
• 5-20% during breast feeding.
•5%-blood products and sexual
abuse
The overall risk of MTCT without intervention is
about 20-45%

The other 55-80% although not HIV infected still have

2-5 fold risk of mortality as direct consequences of
mother’s HIV compared to children born to uninfected
mothers

)
STRATEGIES FOR PMTCT
STRATEGIES FOR PMTCT
Increase the percentage of HIV positive pregnant and
breastfeeding women who receive ARVs.
Ensure access to care and treatment for mothers and
babies living with HIV.
Improve child survival among HIV-exposed and
infected children.
Specific intervention to prevent MTCT
PMTCT services during ANC
Essential ANC for women with HIV infection
 ARV treatment for PMTCT
ARV prophylaxis for infants born to women
receiving ARV treatment
PATHOGENESIS OF HIV/AIDS
 PATHOGENESIS

Major targets are : The immune system.(cells of

the immunity that contains CD4+ receptor)
Immunogenesis of HIV disease.
 It primarily affect the cell mediated immunity

and the hallmark of HIV/AIDS.

 This lead to (1)Severe loss of CD4+ T-cells.

(2)Impairement in the function of

surviving T-Cells(helper)WHY?
…
 Because depletion of CD4+ T-Cells is critical to
the pathogenesis of AIDS.

 CD4+ Molecules has a high affinity receptor for

HIV.

 This explains the selective tropism of the virus

for CD4+ T cells and its ability to infect other
CD4+ T-Cells , particularly Macrophages.
 The initial step in infection is the binding of
gp120 envelop to CD4+ molecule that serves as
primary receptor for HIV.

 However binding to CD4+ not sufficient for

infection.

 It must bind to other cell surface (core receptor)

for entry in cell .
 Recent studies indicate that membrane proteins
called CXCR4 and CCR5 are receptors for
chemokines that serves this role.

 Thus HIV must bind to its primary receptor

CD4+ and its co receptors before fusion with
cell membrane and internalization.
 Importance of co receptor is to over come the
effect of CCR5 since patient with inherited
mutant CCR5 are resistance to HIV-1.

 After internalization, it undergoes reverse

transcriptase to form proviral DNA that is then
integrated into the host genome.
 After this, the provirus may remain locked
into the chromosome for month to years and
hence the infection may become latent.

 Or may be transcribed with the formation of

complete viral particles that bind from the cell
membrane.
Clinical signs & conditions suggestive of HIV
infection in a child
Common in HIV infected, but uncommon in HIV
uninfected child
 Recurrent severe bacterial infection
 Persistent or recurrent oral thrush
 Bilateral parotid enlargement
 Generalized lymphadenopathy
 Hepatosplenomegaly (non-malaria areas)
 Persistent or recurrent fever
 Neurological dysfunction
 Herpes zoster of single dermatome
 Persistent generalized dermatitis
Clinical signs & conditions suggestive of HIV
infection in a child –
Conditions specific to HIV infection
Pneumocystis pneumonia
Oesophageal candidiasis
Extrapulmonary cryptococcosis
Invasive salmonella infection
Lymphoid interstitial pneumonitis
Herpes zoster with multi-dermatomal involvement
Kaposi’s sarcoma
Lymphoma
Progressive Multifocal Leucoencephalopathy (PML)
3 year old with HIV encephalopathy, Failure-To-Thrive, Recurrent
Infections
WHO case definition of PAIDS
Major signs(presence of at least 2)
-failure to thrive
-chronic diarrhoea(>1month)
-prolonged fever(>1month)
- severe or recurrent pneumonia
…
Minor signs(presence of at least 2)
-generalized lymphodenopathy
-oropharyngeal candidiasis
- reccurent common infections : ear, infection
pharyngitis
-persistent cough(in absence of TB disease)
-generalized body rash
-maternal HIV infection
Diagnosis in Children < 18 months
Maternal HIV Ab is passively transferred to infant across the
placenta
Maternal Ab wanes with time but may persist in the infant
up to 18 months
The Ab test is therefore positive at birth in children born to
HIV infected women, including those children that are NOT
infected
This leads to difficulties in interpreting an HIV antibody
positive test result in children < 18 months.
Diagnosing HIV Infection in Children <18 months :
When Virology Tests ARE Available

HIV-exposed infants should have virology testing (PCR)

early, between 4-6 weeks of age, or at the 2nd MCH visit.
DNA PCR & RNA PCR are the most widely available
tests for infant diagnosis

Virology testing is used primarily to identify the infected

child, not to exclude infection in the exposed child.
HIV test Results & Breastfeeding in children <18 mon

For a child that was never breastfed: A single negative PCR test
after the age of 4 weeks excludes HIV infection.

For a child that was weaned for more than 6 weeks prior to
virology (DNA PCR) testing, a negative PCR excludes HIV
infection.

If the child is still breastfeeding, negative PCR does not exclude
HIV infection.
…
A confirmatory testing should be done 6 weeks after
complete cessation of BF to determine the final
infection status.

Negative HIV antibody test in an exposed infant <

18 months suggests that the infant is HIV negative
and should be confirmed at least 3 months after
cessation of breast feeding

If the PCR is positive, encourage mother to continue

BF.
HIV test Results & Breastfeeding in children <18
mon cont.

If the PCR is negative, encourage mother to stop or shorten

duration of BF, if replacement feeding is acceptable
feasible, affordable, sustainable and safe (AFASS).

Repeat the PCR test 6 weeks after complete cessation of BF

or do antibody test if the child is > 18 months

Prophylactic ARVs for PMTCT (mother and/or infant) does

not affect interpretation of a DNA PCR test.
Diagnosing HIV Infection in Children <18 months: When
Virology Tests are NOT Available

A presumptive diagnosis of HIV infection must be

made based on clinical findings

Good Clinical Reasoning can identify children at

high risk for HIV disease & rapid progression

The purpose of making a presumptive diagnosis is to

initiate ART in the sick child.
…
Infants with severe manifestations of HIV infection
should not be denied treatment because their
diagnosis cannot be confirmed.

A presumptive diagnosis of HIV should be made if

an exposed infant present with any stage iii or
stage iv conditions
Diagnosis in Children > 18 months
In children > 18 months diagnosis of HIV infection is
best determined by the detection of antibodies
(markers) to the virus in blood

The antibodies are specific for particular virus proteins

and are unique to HIV

Antibodies are produced by the host in response to

HIV antigens stimulus
HANDLING HIV EXPOSED
INFANT
Exposed infant discovered post delivery
Administer NVP syrup immediately after birth
and continue at appropriate dose until six weeks of
age.

 Infant prophylaxis is most effective when given as

soon as possible after birth –preferably within 6 to
12 hours.

However, NVP syrup may be started between birth

and four weeks of age for infants who present late.

NVP prophylaxis should stop when the infant is

Infant NVP dosing
Low birth weight
infants should
receive mg/kg
dosing, suggested
starting dose is2
mg/kg once daily.
Postpartum care for women with
unknown HIV status
HIV testing and counseling:
Counselling about safer infant feeding:
ARV treatment for mother and ARV prophylaxis
for the infant:
Vitamin A supplementation:
Counseling about infant HIV testing and CPT:
Counseling about postpartum family planning:
Scheduling of comprehensive care visits for the
mother and infant
Use of antiretroviral (ARV) drugs during pregnancy and
Lactating mothers.
The pregnant or breast feeding women
with HIV should be started with lifelong
ART

Tienofovir (TDF)+Lamivudine93TC)+
Efavirenz(EFV).

AZT+3TC+NVP.
Staging for children with
confirmed HIV Infection
Classification of HIV-associated Clinical Disease

World Health Organization (WHO) Clinical staging:

FOUR stages:
Stage 1 – Asymptomatic
Stage 2 – Mild
Stage 3 – Advanced
Stage 4 – Severe
WHO STAGE I
o Asypmtomatic
o Persistent generalized lymphadenopathy (PGL)
WHO Stage 2 (Mild)
Hepatosplenomegaly Lineal gingival erythema
Papular pruritic Angular cheilitis
eruptions Parotid enlargement
Extensive wart virus Herpes zoster
infection Recurrent or chronic
Extensive molluscum URTIs (otitismedia,
contagiosum otorrhea, sinusitis)
Fungal nail infections
Recurrent oral
ulcerations
WHO Stage 3 (Advanced)
 Moderate unexplained  Pulmonary tuberculosis
malnutrition  Lymph node tuberculosis
 Unexplained persistent  Severe recurrent presumed
diarrhoea (>14 days) bacterial pneumonia
 Unexplained persistent  Unexplained anemia (<8
fever (intermittent or g/dL), neutropenia
constant, >1 month) (<1,000/mm3 ), or
 Oral candidasis (outside thrombocytopenia
(<30,000/mm3) for >1mth
neonatal period)  Chronic HIV-associated lung
 Oral hairy leukoplakia disease including
 Acute necrotizing ulcerative bronchiectasis
gingivitis/periodonitis  Symptomatic LIP (Lymphoid
interstitial pneumonitis)
WHO Stage 4 (Severe)
Unexplained severe  Kaposi’s sarcoma
wasting or severe  Oesophageal candidiasis
malnutrition not  Extrapulmonary
responding to standard cryptococcosis including
therapy meningitis
Pneumocystis pneumonia  Any disseminated endemic
Recurrent severe presumed mycosis
 Cryptosporidiosis
bacterial infections
 Isosporiasis
(excluding pneumonia)
Chronic HSV infection  Disseminated non-
tuberculous mycobacterial
(lasting >1 mo)
infection
 Extrapulmonary TB
Stage 4 (cont)
Candida of trachea, HIV-associated
bronchi or lungs cardiomyopathy or
Acquired HIV-associated HIV-associated
rectal fistula nephropathy
Cerebral or B-cell non- HIV encephalopathy
Hodgkin Lymphoma CMV infection
Progressive Multifocal CNS toxoplasmosis (> 6
Leukoencephalopathy weeks of life)
(PML)
 Immunological Staging

 To identify children needing immediate ART

 The WHO has developed a system of classifying

the level of immune deficiency for HIV infected
children using their absolute CD4 count or CD4
percentage.
Immunological Staging
Four immunological stages in progressive HIV
disease in children:
1. Not significant immunosuppression
2. Mild immunosuppression
3. Advanced immunosuppression
4. Severe immunosuppression
NOTE: CD4 counts CHANGES with age
in children < 6 years
CD4 percentage does not change with age
 Classification of HIV-associated immunodeficiency in children

Age-related CD4 values

HIV-associated
immunodeficien 0-11 12-35 36-59 > 5years
cy months months months
(%) (%) (%)
Not > 35 > 30 > 25 > 500
significant
Mild 30-35 25-30 20-25 349-499

Advanced 25-30 20-25 15-19 200-349

Severe < 25 < 20 < 15 < 200 or 15%

ART INITIATION

AIM
Increase survival
&
Improve quality of life
TYPES OF ANTIRETROVIRAL
DRUGS
Nucleoside reverse transcriptase inhibitors (NRTIs)

Non-nucleoside reverse transcriptase inhibitors

(NNRTIs)

Nucleotide reverse transcriptase inhibitors

(Nucleotide analogues)

Protease inhibitors (Pls)

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Zidovudine (AZT),

Lamivudine (3TC),

Emtricitabine (FTC)

Abacavir (ABC),
Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
Efavirenz (EFV)

Nevirapine(NVP)
Nucleotide Reverse Transcriptase Inhibitors (Nucleotide
analogues)

Nucleotide analogues resemble NRTIs

and an example of this relatively new
classof antiretroviral drugs is

Tenofovir (TDF).
Protease Inhibitors (PIs)
Atazanavir (ATV).

Lopinavir (LPV),

Ritonavir (usually used as a

booster with above mentioned PIs)
WHEN TO STAT ART?
All HIV infected pregnant women and lactating
mothers are eligible for ART regardless of CD4 count
Initiation of ART for children under 15 years

 Confirmed diagnosis of HIV:

All children below fifteen years of age
who have a confirmed diagnosis of HIV, regardless of
WHO clinical stage or CD4 cell count.

Presumptive HIV infection:

All HIV exposed children aged less than 18 months with
a presumptive HIV infection. ( have a positive rapid
antibody test and meets WHO
Initiation of ART for Adolescents 15 years or older

All children 15 years and older infected

with HIV with severe or advanced
symptomatic disease (WHO clinical
stage 3 or 4) regardless of age and CD4
cell count.

All children older than 15 years in

Stage 1 or 2 with CD4 <500 cell/mm3
What Drugs to Start With (Naïve)
ART usually involves a combination of three
antiretroviral drugs from different classes

The following combinations are preferred.

2 NRTIs + 1NNRTI
2 NRTIs + PIr (RTV boosted PI)
first line ART Regimen for children younger
than 3 years
The first line regimen for
children over 3 years old
Reasons for Changing ARV Therapy
in Infants and Children
Clinical criteria for treatment
failure

Immunological Criteria for

treatment failure

Virological Criteria for treatment

failure
Summary of recommended first- and second-
line ART regimens in children < 15 years
Specifically Because of poor palatability of LPV/r. In
this case, switching to a second line NVP-based
regimen should be considered.
Based on the recent approval of the use of EFV in
children less than 3 years, an EFV-based regimen could
be considered as an alternative.
 TDF may only be given to children > 2 years
 ATV/r can be used as an alternative to LPV/r in
children older than 6 years
How to Monitor therapy
Clinical
Laboratory
Side effects/toxicity
Treatment adherence
Appointment adherence
Psychological
WHO recommendations for
laboratory monitoring
Essential baseline – HIV test, Hematocrit
Desirable – FBC (including total lymphocyte count),
LFT’s, RFTs, lipid profile, blood glucose
If available – CD4 count or %
Optional – Viral load
Prophylaxis of opportunistic infections
Many opportunistic infections can be prevented by
using cotrimoxazole prophylaxis particular in the case
of
-Bacterial pneumonias
-PCP
-Toxoplasmosis
-TB
Indications for prophylaxis using co-
trimoxazole

HIV exposed children

-All children born to HIV positive women starting at
four wks of life or as soon as possible thereafter and
maintained in the 1st 18months of life unless proven
HIV negative and mother has stopped breastfeeding
completely

)
 Co-trimoxazole

HIV INFECTED CHILDREN

-Children ≥ 12 months with confirmed HIV infection
regardless of CD% or clinical stage
-Children 1-4 years who have symptomatic HIV(WHO
stage 2,3 or 4) regardless of their CD4%
-Children 1-4 years and have CD4<25% regardless of their
clinical stage
-All HIV infected chilren >5 yrs old should start or
continue CTX according to adult guildelines.
 PREVENTION AND
MANAGEMENT OF PAIDS
Cotrimoxazole formulation and dosage for HIV-infected or HIV-
exposed children
Suspensio Single- Double-
Paediatric
n strength adult strength
RECOMMENDED tablet
(5 ml syrup tablet adult tablet
DAILY DOSAGE (100 mg/20
[200 mg/40 (400 mg/80 (800 mg/160
mg)
mg]) mg) mg)
<6 months 2.5ml One tablet ¼ tablet, —
100 mg SMX/20 mg possibly mixed
TMP with feeding

6 months–5 years 5 ml Two tablets Half tablet —

200mg SMX/40 mg
TMP
>6–14 years 10 ml Four tablets One tablet Half tablet
400 mg SMX/80 mg
TMP

>14 years — — Two tablets One tablet

800 mg SMX/160
mg TMP

Frequency: once a day

Isoniazid Preventive Therapy in children

In order to prevent active TB, children should be considered

for IPT as follows:
All newborns with no symptoms of active TB disease that
are born tomothers with active TB disease.
 All HIV-infected children less than 12 months with no
symptoms of activeTB disease and with a known TB contact.
•All HIV-infected children who are 12 months or older with
no symptoms ofactive TB disease.

Note: IPT should be initiated only after TB disease has

been ruled out
Other exclusion criteria for IPT include:

• Alcohol abuse
• Non-adherence to long term treatment
• Current/ past history of hepatitis
• Medical contra- indication to INH
• Terminal AIDS (WHO clinical stage 4)
IPT should only be offered in the following situations:

Where quality supportive counselling is

available
After effective screening for active TB
Where there is capacity for follow up and
monitoring of patients to encourage
adherence to preventive therapy.
Where there is capacity to manage side
effects and exclude active TB during IPT
FOR SMALL CHILDREN
Isoniazid: 10 mg/kg (10-15
mg/kg) daily for 6 months
• Pyridoxine: 1-2 mg/kg daily
until neuropathy subsides
Dosage:

Isoniazid: 300 mg daily for 6 months

to complete one cycle of IPT (IPT
should be repeated after two years
from the last IPT cycle
 Pyridoxine: 25mg daily until
neuropathy subsides
PEP
Timing of Post Exposure Prophylaxis (PEP)

PEP should be initiated as soon as

possible preferably within 2 hours after
exposure.
Studies suggest that PEP may be
substantially less effective if started
more than24-36 hours post-exposure
and not effective after 72 hours.
Recommended Regimen for HIV PEP Following
Occupational
and Non-Occupational Exposures
Recommended treatment regimens for
children.
Give a child a chance

Early Intervention is the key