HIV AND AIDS IN CHILDREN

by D.Zulu
 Introduction

• Since the first cases of human immunodeficiency

virus (HIV) infection were identified, the number of
children infected with HIV has risen dramatically in
developing countries, the result of an increased
number of HIV-infected women of childbearing age
in these areas.
• HIV is a retrovirus and can be transmitted vertically,
sexually, or via contaminated blood products or IV
drug abuse. Vertical HIV infection occurs before
birth, during delivery, or after birth.
 MODES OF TRANSMISSION OF HIV TO CHILDREN

• The following are the ways in which a child can

get infected with HIV:
• MTCT – 95% of infected infants
• Sexual transmission (adolescents/abuse)
• Transfusion of infected blood and its products
• Unsterile injection procedures
• Traditional practices
 DIAGNOSING HIV IN CHILDREN

• The definitive diagnosis of HIV infection in

children at any age requires diagnostic testing
that confirms the presence of HIV.
• For Children ≥ 18 months an antibody testing
is done and for children < 18 months you have
to do the Virologic testing (PCR).
• Infants infected in utero usually have detectable HIV on
virological testing at birth. Infants infected at or around
delivery usually have undetectable HIV on virological
testing at birth, and may take a short time (e.g. 1 – 2
weeks) before the virus is detectable by virological assays.
• Therefore, early determination of HIV exposure and
definitive diagnosis is critical to allow early initiation of
potentially lifesaving ART. The identification and follow-up
of infants born to women known to be HIV infected is a
necessary first step in infant diagnosis.
• It is recommended that routine counselling and
testing (DCT) be offered to all children who come
into contact with a healthcare worker.
• This is especially important where high rates of HIV
exposure are anticipated but have not previously
been identified for various reasons (e.g. low
coverage of maternal antenatal care [ANC] testing,
lack of testing facilities and other infrastructure, or
where testing was not previously accepted by the
community).
 Cont…
• It is strongly recommended that HIV
virological testing be used to diagnose HIV in
infants and young children less than 18
months of age.
 Cont…
• Initial virological testing should occur at the time of
the first under five clinic visit, at age 6 weeks. By the
age of 4 weeks, virological testing approaches 98%
sensitivity.
• Testing at 6 weeks of age will therefore; identify the
vast majority of infants infected in utero and
intrapartum.
• Delaying testing beyond this time delays diagnosis
and puts HIV-infected infants at risk for disease
progression and death.
 Cont…
• Testing earlier than 4-6 weeks of age may be less
sensitive for cases of peripartum transmission.
• For infants less than 6 weeks of age with unknown
HIV exposure, it is strongly recommended to
provide HIV serological testing to mothers or their
infants in order to establish exposure status.
• Positive test results should be fast-tracked to the
mother-baby pair as soon as possible to enable
prompt initiation of ART
 Laboratory Diagnosis

• Laboratory diagnosis can be done using

antibody test and Virological tests.
 Antibody tests

• Maternal HIV antibody passively transferred to

infant across the placenta
• Maternal antibody wanes with time (6-18
months)
• Antibody test is positive at birth in ALL
children born to HIV infected women,
including those children that are NOT infected
• False positive results thus seen
 Diagnosis

• Child ≥ 18 months: 2 or more antibody tests after 18 months

confirm diagnosis.
• Child < 18 months
• Positive antibody test may be a false positive result
reflecting maternal antibodies.
• An alternative test therefore required to confirm the
diagnosis
• A negative HIV antibody test in an exposed infant < 18
months suggests that the infant is HIV negative and should
be confirmed at least 6-12 weeks after complete cessation of
breast feeding
 Virologic tests

• Virologic tests – detect HIV virus (DNA, RNA, or proteins) in blood

• They are the ideal method of HIV diagnosis in children < 18
months
• If test is positive: refer immediately for ART and repeat PCR to
confirm infection
• If test is negative and child is not breastfeeding, HIV is excluded
by one negative virological tests at age >6 weeks
• If breastfeeding and initial test is negative, test should be
repeated at 6 months
• Children with negative virologic tests should have a rapid
antibody test performed at age ≥ 18 months
 WHO STAGING OF CHILDREN

• Staging provides a guide to prognosis and

interventions needed at the different stages
• And it also provides guidance in monitoring
response to therapy (treatment failure or
improvement).
WHO classification of HIV-associated clinical disease

CLASSIFICATION WHO
ASYMPTOMATIC 1
MILD 2
ADVANCED 3
SEVERE 4
• Clinical Stage 1
• Asymptomatic
• Persistent Generalised Lymphadenopathy
(PGL)
• Clinical Stage 2
• Unexplained persistent Hepatosplenomegaly
• Papular pruritic eruptions (itchy rash)
• extensive wart virus infection
• extensive molluscum contagiosum
 Cont…
• Recurrent oral ulcerations
• Unexplained persistent parotid enlargement
• Lineal gingival erythema
• Herpes zoster
• Recurrent or chronic upper respiratory
infections (otitis media, otorrhoea, sinusitis,
tonsillitis)
•  
 Clinical Stage 3

• Moderate unexplained malnutrition not adequately

responding to standard therapy
• Unexplained persistent diarrhoea (14 days or more )
• Unexplained persistent fever (above 37.5 intermittent
or constant, for longer than one month)
• Persistent oral Candida (outside first 6-8 weeks of life)
• Oral hairy-leukoplakia
• Acute necrotising ulcerative gingivitis/periodontitis
• Lymph node TB
• Pulmonary TB
• Severe recurrent presumed bacterial pneumonia
• Symptomatic lymphoid interstitial pneumonitis (LIP)
• Chronic HIV-associated lung disease including
bronchiectasis
• Unexplained anaemia (<8g/mm 3/dl ),
• neutropenia (<500 or
• chronic thrombocytopenia (<50 000/mm3)
 Clinical Stage 4

• Unexplained severe wasting, stunting or

severe malnutrition not responding to
standard therapy
• Pneumocystis pneumonia
• Recurrent severe presumed bacterial
infections (e.g. empyema, pyomyositis, bone
or joint infection, meningitis, but excluding
pneumonia)
• Chronic herpes simplex infection; (orolabial or
cutaneous >one month' s duration or visceral at
any site)
• Extra pulmonary TB
• Kaposi sarcoma
• Oesophageal candidacies (or Candida of trachea,
bronchi or lungs)
• CNS toxoplasmosis (outside the neonatal period)
• HIV encephalopathy
• CMV infection; retinitis or infection affecting
another organ, with onset at age >1 month.
• Extra pulmonary cryptococcosis including
meningitis
• Disseminated endemic mycosis Chronic
Cryptosporidiosis
• Chronic Isosporiasis
•  
• Disseminated non-tuberculous mycobacteria
infection
• Acquired HIV-associated rectal fistula
• Cerebral or B cell non-Hodgkin lymphoma
• Progressive multifocal leukoencephalopathy
• HIV-associated cardiomyopathy or
• HIV-associated nephropathy
 CLINICAL COURSE OF HIV INFECTION IN CHILDREN

• Category 1 (25 – 30%): Rapid progressors

• Rapid disease progression; infants die within 1 year.
• Disease acquired in-utero or perinatally.
• Category 2 (50 – 60%): Slow progressors
• Children who develop symptoms early in life.
• Deteriorate and die by 3 to 5 years.
• Category 3 (5 – 25%): Long-term survivors
• Long-term survivors who live beyond 8 years of age.
 Management of child with HIV and AIDS.

• FIRST LINE ARV FOR CHILDREN

• For children infected with HIV three years and
older (including adolescents), EFV is the
preferred NNRTI for first-line treatment and
NVP is the alternative.
 Cont…
• For children infected with HIV three years to
less than 10 years old (or adolescents less
than 35 kg), the NRTI backbone for an ART
regimen should be one of the following, in
preferential order:
• ABC + 3TCAZT or
• TDF + 3TC (or FTC)
• For adolescents infected with HIV (10 to 19
years old) weighing 35 kg or more, the NRTI
backbone for an ART regimen should align
with that of adults and be one of the
following, in preferential order:
• TDF + 3TC (or FTC)
• AZT + 3TC
• ABC + 3TC
SUMMARY OF FIRST LINE REGIMEN

  Children 3 years to less Adolescents (10 to 19 years)

than 10 ≥35 kg
years and adolescents <35  
kg
 
PREFERRED ABC+ 3TC + EFV TDF + 3TC (or FTC) +EFV
   
ALTERNATIVES ABC + 3TC + NVP AZT + 3TC + EFV
AZT + 3TC + EFV AZT + 3TC + NVP
AZT + 3TC + NVP TDF + 3TC (or FTC) +NVP
TDF + 3TC (or FTC) +EFV  
TDF + 3TC (or FTC)+NVP
 
SPECIAL CIRCUMSTANCES   ABC + 3TC + EFV
ABC + 3TC + NVP
 
 Second line ARV’s for children

• Second line regimen will be prescribed to a

child who has not responded to first line
treatment. The recommended 2nd line
regimens in Infants and Children with
treatment failure of 1st-line regimens is as
follows:
• After failure of a first-line NNRTI-based
regimen, a boosted PI plus two NRTIs are
recommended for second-line ART; LPV/r is
the preferred boosted PI.
 Cont…
• After failure of a first-line LPV/r-based regimen,
children younger than 3 years should remain on
their first-line regimen, and measures to improve
adherence should be undertaken.
• After failure of a first-line LPV/r-based regimen,
children 3 years or older should switch to a
second-line regimen containing an NNRTI plus
two NRTIs; EFV is the preferred NNRTI.
 Cont…
• After failure of a first-line regimen of ABC or
TDF + 3TC (or FTC), the preferred NRTI
backbone option for second-line ART is AZT +
3TC.
• After failure of a first-line regimen containing
AZT or d4T + 3TC (or FTC), the preferred NRTI
backbone option for second-line ART is ABC or
TDF + 3TC (or FTC).
 Recommended second-line regimen:
boosted PI + two NRTI
First-line regimen Preferred second-line regimen
at failure
AZT/D4t + 3TC + NVP/EFV ABC + 3TC + LPV/r or
TDF + FTC/3TC + LPV/r (in children > 12yrs old)

ABC + 3TC + NVP/EFV AZT + 3TC + LPV/r

ABC + 3TC + AZT/d4T 3TC + EFV/NVP + LPV/r or

TDF + FTC/3TC + LPV/r (in children > 12yrs; in consultation with specialist)

AZT/d4T + 3TC + LPV/r ABC + 3TC + NVP/EFV (in consultation with specialist)

ABC + 3TC + LPV/r AZT + 3TC + NVP/EFV (in consultation with specialist)
 DRUG FORMULATIONS

• Antiretrovirals (ARVs) are developed for adults, most

clinical trials are in adults, with doses and dosage
forms designed for adults. But children cannot be
dosed like small adults, as their metabolic capacity to
absorb ARVs is not simply proportional to their weight.
• Safety, efficacy and dosage need to be determined via
specific pediatric trials.
• Most ARVs were developed in tablet form, yet these
are impractical for children under five, who require
special liquid formulations. While older children can
take tablets, those intended for adults often contain
too large a dose.
 Cont…
• Optimal dosing is given for single ARV drugs and
where possible combination solid fixed dose
combinations.
• Dosing for ART is based on weight or body surface
area (BSA). Use of BSA-guided dosing is not feasible
in many settings. Weight-based dosing is more
acceptable. Weight-based conversions for BSA have
been developed. These estimations risk: Toxicity if
dose is too high. Development of resistance if dose
is too low
 Fixed dose combination

• Fixed dose combination

• The FDC available for children are:
• 3TC/d4T/NVP 30/6/50mg
• 3TC/d4T/NVP 60/12/100mg
• 3TC/d4T 30/6mg
• 3TC/d4T 60/12mg
• LPV/r 100/25mg