PEDIATRIC

HIV/AIDS
Kussia.A [MD]
HIV virology and pathogenesis

 HIV 1 and HIV 2 are retroviridae family

 Single stranded RNA
 HIV 1 has different gene regions
 GAG region-encodes core proteins(p24,p17,p9,p6)
 POL region-viral enzymes(reverse transcriptase,
integrase,protease,protease)
 ENV region-envelope proteins( gp120,gp41)
 Other regulatory genes
HIV entry in to the cell

 Attachment
 Fusion
 Reverse transcription
 Integration
 Synthesis of viral proteins
 cleavage
 Assembly
 Budding
General Principles of
Immune Dysfunction in HIV
 All elements of immune system are affected
 Advanced stages of HIV are associated with
substantial disruption of lymphoid tissue
 Impaired ability to mount immune response to new antigen
 Impaired ability to maintain memory responses
 Loss of containment of HIV replication
 Susceptibility to opportunistic infections
Mechanisms of CD4
Depletion and Dysfunction
 Direct
 Elimination of HIV-infected cells by virus-specific immune responses
 Loss of plasma membrane integrity because of viral budding
 Interference with cellular RNA processing
 Indirect
 Syncytium formation
 Apoptosis
 Autoimmunity
 The clinical course of HIV infection has three stages.
 Primary HIV infection
 Asymptomatic stage/latent infection
 AIDS
 
Natural history of pediatric HIV

Rapid progressers -15-25% of infected children in

developing countries
 Median survival 6-9 months if not treated
Typical progressors/slow progressors -60-80%
 Median survival is 6 yrs
Long term survivors- < 5%
 No progression for more than 8 yrs
 HIV /AIDS AND PMTCT
EPIDEMIOLOGY
 1983-1985 1st cases of pediatric HIV were found in
Ruwanda, Democratic Repobulic of Congo and
Uganda.
 1988 the 1st pediatric HIV clinic started in Uganda.
 Global Pediatric HIV: 2007 UNAIDS/WHO

 Children (15years) living with HIV = 2.1 million

 Number of children who died of AIDS = 290,000

 New infections among children = 420, 000

 90% of HIV positive children liven in Sub-Saharan

Africa

International Center for AIDS Care and Treatment Programs, Columbia University
Pediatric HIV:Ethiopia

 The 1st HIV exposed new born identified in 1986.

 Fee ARVs started 2002-2003.
 In 2005 pediatric ARVs formulations available on
free basis.
 Pediatric HIV/AIDS in Ethiopia
single point estimate, 2008
 68,136 children are estimated to live with HIV
 14,093 new infections
 17, 264 are in immediate need of ART
 9,284 AIDS deaths
 Children on ART account only for 4.7 of total
individuals on ART
 886,820 AIDS Orphans live in 2008

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 Current prevalence…….
 According to HIV Related Estimates and Projections
for Ethiopia, the national prevalence of HIV
infection in 2014 is 1.2 % (1.6% for females and
0.8% for men) among adult population
 The trends show that the rate of epidemic has been
declining significantly.
 Diagnosis of HIV in
Infants and Children
 Babies can acquire HIV infection during:

Pregnancy Labor & delivery Breastfeeding

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 Mother to child transmission (vertical ) 90%
 Mother-to-Child transmission can occur during
pregnancy, labour and delivery and breastfeeding.
 Not all HIV infected women will automatically
transmit the virus to their child
 Over all risk is 35%( pregnancy,labor and delivery
20%, breast feeding 15%)
Complexities of Infant Diagnosis

 HIV infection is difficult to diagnosis in infants:

- Routine HIV antibody tests cannot be used
- Specialized virologic tests are necessary
- Clinical diagnosis requires frequent and close follow-up of the infant
 HIV infection is difficult to exclude in infants:
 Infants who breastfeed continue to be at risk for acquiring HIV infection

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Complexities of HIV Diagnosis: Antibody Testing

 All infants born to HIV+ mothers will test HIV antibody positive
in the first several months of life

 A positive HIV antibody test in infants <18 months of age will

not distinguish whether or not the infant is HIV-infected.

 If the child is not infected the HIV antibody fades during first 6 -
18 months of life

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Complexities of HIV Diagnosis: Virologic
Tests
 Specialized virologic tests must be used
 HIV DNA PCR
 HIV RNA PCR
 p24 Antigen
 Viral Culture
 Two positive virologic tests = HIV infection
 One positive virologic test = Presumed HIV infection

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Presumptive diagnosis of severe HIV diseases in
< 18 months

 HIV antibody positive infant with:

 diagnosis of stage 4 or any AIDS defining condition
 OR
 Symptoms with two of the following
 Oral thrusha
 Severe pneumoniab
 Severe sepsisc
 Supporting factors are
 Recent maternal death
 Advanced HIV disease in the mother
 Cd4 percentage of infant < 20%
Diagnosing HIV in the Child >18 Months

 HIV antibody should be used to diagnose HIV

infection in children > 18 months of age
 Children >18 months with positive antibody test
have HIV infection

 A negative antibody test in children > 18 months

excludes HIV infection
 Except in cases of continued breast feeding. Antibody should be repeated 6-
12 weeks post cessation of breast feeding

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Diagnostic Algorithm for Infants
< 18 months of age
Infant 6 weeks of age
Or at first clinic visit

HIV DNA PCR

DNA PCR NEGATIVE

HIV DNA PCR POSITIVE
HIV-INFECTED
Continue CTX and close follow-up

•Do not WAIT. Refer for HIV care &

treatment IMMEDIATELY WELL Infant
•Start/continue cotrimoxazole prophylaxis

HIV Rapid Antibody

at ≥ 12 months of age and
or >6-12 weeks after
weaning

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Opportunistic Infections (OI)

 Generally occur with severe immune suppression,

some occur at higher CD4 counts
 Young children have primary infection rather than
reactivation
 Lack of immunity leads to more severe course than
in adults

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 Recurrent bacterial infections
 Account for about 20% of AIDS defining illness in
children.
 Most are caused by encapsulated organism such as
st.pneumonia and salmonella others staphylococcus
aureus , enterococcus etc.
 Common serious infections are pneumonia
,sepsis ,meningitis ( 50% of infections ).
…….infections con’d

 Clinical features similar to non-HIV infected children

.
 May have protracted ,fulminant course with rapid
progression.
 Management is similar to non-HIV infected
children ,may require longer duration of treatment.
 Common OIs: Pneumocystis Pneumonia
(PCP)
 Parasitic infection
 Pneumocystis jeroveci (formerly
Pneumocystis carinii)
 Diffuse and severe
pneumonia
 Peak incidence is between
the age of 3 – 6 months
 Characterized by gradual  Normal CXR/or there may be
onset of hypoxia, fever, cough diffuse alveolar disease with
and respiratory distress granular pattern

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Management

 Intravenous/oral 15-20 mg of trimethoprim and 75-

100 mg sulfamethoxazole/24hrs in to four divided
doses for 21 days.
 If severe hypoxia prednisolone 2mg/kg /24hrs for 7-
10 days then tapper over 7-14days.
 Secondary prophylaxis life long after infection
 Oral candidiasis
 Is the most common oral condition in HIV infected children.
 Three forms -atrophic candidiasis
- hyperplastic (Pseudomem
brarnus )
- angular chelitis
 Dysphagia indicates involvement of esophagus.
Management

Oropharyngeal
 Nystatin 1oo,ooo units/ml 1-2ml 4x /day
 Oral miconazole gel 2.5ml 2x/day
 Fluconazole 3-6mg/kg 7-14 days
Esophageal
 Fluconazole 6mg/kg day one then 3-6mg/kg for 14-21 days.
Common skin diseases

Molluscum contangiosum
 Common child hood viral infection characterized by discrete, dome
shaped ,centrally umblicated papules.
 Transmission skin to skin
 In HIV infected covers 5% of
body surface.
TREATENT

 Liquid nitrogen
 Curettage
 HAART
Other skin diseases
 Scabies
 Seborrheic dermatitis
 Herpes zoster
CNS manifestations

 Occur in 50-90% of perinatally infected children.

 Progressive encephalopathy
developmental delay/regression
acquired microcephally
cognitive deterioration
CT –cerebral atrophy
 Focal neurologic signs
CNS lymphoma,tuberculoma,stroke ,toxoplasmosis
Cardiovascular manifestations

 Dilated cardiomyopathy
 Persistent tachycardia
 Left ventricular hypertrophy
 Cardiac complications indicate poor prognosis.
 GI manifestations
 Chronic /reccurent diarrhea ,dysphagia
 Pathogens include:
 Bacteria (salmonella, campaylobacter ,MAC)
 Protozoan (giardia ,cryptosporidium
,isospora,microsporidia)
 Viruses ( CMV ,Rota virus ,HSV)
 Fangal ( candida)
o Hematologic manifestations
 Un explained anemia
 Leukopenia
 thrombocytopenia
c

o Malignancies
 less than 2% of AIDS defining illness in children
 NHL
 Primary CNS lymphoma
 Kaposis sarcoma
 ALL
WHO Staging of pediatric HIV/AIDS

oStage I
 Asymptomatic
 PGL
oStage II
 Recurrent URTI (otits media,sinusitis ,tonsilits)
 Extensive molluscum ,HZ
 Seborrheic dermatits
 Persistent hepatosplenomegally
oStage III
 Oral candidiasis
 Necrotizing ulcerative gingivitis
 Unexplained Persistent fever
 Persistent diarrhea
 Un explained anemia, leukopenia
,thrombocytopenia
 Moderate malnutrition
 Pul.TB ,recurrent bacterial pneumonia ,LIP
oStage IV
 Severe malnutrition not responding to standard RX
 Extra pulmonary TB
 Candidiasis of esophagus ,trachea ,bronchi
 PCP
 HIV associated cardiomyopathy ,nephropathy
 Recurrent severe bacterial infections
( meningitis ,pyomyositis ,empyema)
 CMV infection.
Pediatric antiretroviral therapy

o Goals of pediatric ART

 Maximal and durable suppression of HIV
 Restoration/preservation of immune function
 Reduction of HIV related morbidity and mortality
 Preserve normal growth and development
 Improve quality of life
 WHO Criteria for ART Initiation in Infants
and Children < 15 years
 All children of age < 15 years with HIV infection regardless of CD4 count and
WHO clinical stage
 HIV exposed infant <18 months meeting the WHO criteria for Severe HIV
disease in the absence of virologic test

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 Prior to ART Initiation-Clinical Evaluation

 Confirm HIV Diagnosis

 Laboratory confirmation as soon as possible
 WHO Clinical and Immunological Staging Criteria
 Baseline growth measurements
 Height and weight on all children
 Head circumference for children < 2 years of age
 Baseline neurodevelopmental status
 Screen for and treat any inter-current or opportunistic infection
 Ensure access to nutrition and prophylaxis

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Prior to ARV Initiation – Laboratory
Evaluation
 CD4 count
 Full blood count
 Liver function test: SGPT ,SGOT
 Kidney function: Serum creatinine
 TB screening
 History
 Mantoux test and Chest x-ray if available
 When available: viral load

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Prior to ART Initiation-Adherence
Preparation
 Identify and fully counsel care givers
 Confirm availability of support services (family, social, inpatients care
etc)

 Identify barriers to treatment for the care taker and address where
possible
 Prepare family and child for adherence
 Address disclosure where appropriate

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oPediatric 1st line regimens
 2NRTI † 1NNRTI for children> 3yrs and 2NRTI+ 1PI
for < 3yrs of age
 Children less than 3yrs
 ABC + 3TC + LPV/r
 AZT + 3TC + LPV/r
 Children older than 3yrs
 ABC+ 3TC + EFV
 AZT + 3TC + EFV
Treatment failure

Clinical failure
 New or recurrent clinical event indicating advanced or severe
immuno defiency (WHO clinical stage 3 and 4 clinical condition with
exception of TB) after 6 months of effective treatment
Immunologic failure Children
 Younger than 5 years
 Persistent CD4 levels below 200 cells/mm3 or <10%
 Older than 5 years
 Persistent CD4 levels below 100 cells/mm3
Virologic failure
 Plasma viral load above 1000 copies/ ml
Mother to child transmission of HIV

 MTCT is the largest source of HIV infection in

children less than 15 years of age.
 HIV transmission rates from mother to child is
estimated to be 25-45%.
 During pregnancy 5-10%
 During labor 10-15%
 During breast feeding 20%
Factors Influencing MTCT

 Viral Load
 The higher the viral load, the higher the risk of MTCT
 Lower risk through:
 Use of ART during pregnancy and postpartum to mother and newborn
 Adequate nutrition, particularly vitamin A

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Factors Influencing MTCT (2)

 Maternal factors increasing risk:

 Viral or parasitic placental infection (especially malaria)
 Becoming infected with HIV during pregnancy
 Severe immune deficiency
 Advanced clinical and immunological state
 Maternal malnutrition

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 Labor and delivery factors
_prolonged rupture of membrane(>4hrs)
_chorioaminionitis
_episiotomy
_instrumental delivery
_delayed infant cleaning and eye care
_routine air way suctioning
_twin pregnancy
 Infant factors and feeding practices
_premature and low birth weight
_mother infected while breast feeding
_mixed feeding
_breast lesions or infant oral lesions
_prolonged breast feeding
PMTCT
ARV prophylaxis to give to non-eligible
pregnant women

2 possible options:
A) Maternal AZT, or
B) Maternal triple ARV prophylaxis
B+) Maternal triple ARV life long
And for the breastfeeding mother:
 Provision of ARVs to the child OR the mother
to reduce risk of HIV transmission during
breastfeeding (if breastfeeding is best infant
feeding option)
Prophylaxis options
Option A Option B
Mother Mother
• Antepartum AZT (from 14 weeks) • Triple ARV (from 14 wks until one wk
• sd-NVP at onset of labour* after all exposure to breast milk has ended)

• AZT + 3TC during labour & delivery* • AZT + 3TC + LPV-r

• AZT + 3TC for 7 days postpartum* • AZT + 3TC + ABC
• AZT + 3TC + EFV
• TDF + 3TC (or FTC) + EFV
Infant
Breastfeeding population Infant
• Daily NVP (from birth until one wk after All exposed infants
all exposure to breast milk had ended) • AZT for 4-6 weeks OR
Non-breastfeeding population • NVP for 4-6 weeks
• Sd-NVP + daily AZT for 4-6 weeks
OR
• Daily NVP for 4-6 weeks

*sd-NVP and AZT+3TC can be omitted if mother receives > 4 wks AZT antepartum
Infant Feeding in the context of maternal HIV
infection

 Consequences of under nutrition

 Illness and mortality
 Mortality is high in underweight children
 Underlying cause of 60% of under 5 deaths
 Two-third of deaths occur in <12 months
 Reduced intellectual development
 Poor school performance
 Reduced productivity
Peak age of malnutrition
National recommendation

 Follows the global strategy on infant and young child feeding

recommendations
 EBF for the first 6 months
 Prompt treatment of breast problems
 Avoidance of mixed feeding during the first 6 months
 Ensure that mother is adherent to ART
 After 6 months
 Introduce complementary diet at 6 months of age
 Continue breastfeeding until 12-18 months of age
 Breastfeeding should only be stopped once a
nutritionally adequate and safe diet without breast-
milk can be provided.