PEDIATRIC HIV/AIDS

Ephrem L. (Pediatrician)

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 Human Immunodeficiency Virus
(Acquired Immunodeficiency Syndrome)

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Global situation of HIV/AIDS

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At the end of 2010, an estimated 34 million people [31.6
million–35.2 million] were living with HIV worldwide

Eastern Europe
Western & & Central Asia
North America Central Europe
820,000
1.4 million
East Asia & Pacific
1.5 million
770,000

North Africa South

Caribbean & Middle East & South-East Asia
240,000 460,000 4.1 million

Sub -Saharan Africa

Latin America 22.9 million (68%)
1.4 million
Australia
& New
Zealand
57,000

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The Global AIDS Epidemic
• People living with HIV(PLHIV):
• Total: 34 million [31.6 – 35.2 million] , 1/3 b/n 15-24yrs
• Adults: 30.8 million [29.2 – 32.6 million]
• Children under 15 years: 2.5 million [1.6 – 3.4 million]---
7.4%
• Women: 15.9 million [14.8 – 17.2 million] –52%
Young women esp vulnerable

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The Global AIDS epidemic
• The overall growth of the global AIDS epidemic
appears to have stabilized
• Decreasing new HIV infection (including in children
due to PMTCT)
• The number of people dying of AIDS-related causes
fell to 1.8 million [1.6 million–1.9 million] in 2010.
- Number one cause of mortality in Africa
• The number of people living with HIV worldwide has
increased

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• There were 2.7 million [2.4 million–2.9 million] new
HIV infections in 2010. >90% in developing countries
• Estimated 390 000 [340 000–450 000] among
children

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Global HIV trends, 1990 to 2010

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Global HIV trends, 1990 to 2009

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Pediatric HIV disease remains a major global health
issue
• The burden of pediatric HIV disease is high, despite PMTCT
• 2.3 million children currently living with HIV
• This represents 7.5% of the total number of people with HIV
• 370,000 new pediatric infections globally in 2009
• This represents 15% of the total number of new infections each year
• Mortality in untreated children is very high
• 260,000 deaths in children with HIV annually
• Without treatment:
• 30% of HIV+ infants die by age 1
• 50% of infected children will die before age 2
• Treatment and PMTCT interventions can reduce MTCT rates to <5%
• But in 2009 only 50% of HIV+ pregnant women had access to PMTCT
• And 30% of those received suboptimal prophylaxis with sd-NVP
• Overall, pregnant women have the poorest access to treatment with only 15% of those who
are eligible on ART 10
Interventions to test and treat children lag significantly
behind adults
• Early infant diagnosis (EID) is essential to identify infected infants
• But despite significant scale up - only 15% of HIV-exposed infants have access
to EID
• Treatment is a life-saving intervention and all infected infants and
children < 2 years are eligible for treatment
• Only 28% of children in need of treatment are on ART (compared to 37%
eligible adults)
• Access for infants is even lower
• Adolescents living with HIV are a growing group in need of services

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 Regional situation of
HIV/AIDS: sub-Saharan
Africa

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HIV trends in sub-Saharan
Africa:
The total number of new HIV infections in sub-Saharan Africa
has dropped to 1.9 million [1.7 million–2.1 million] from the
estimated 2.6 million [2.4 million–2.8 million] at the height of
the epidemic in 1997.

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HIV trends in sub-Saharan Africa:
Number of AIDS related deaths decreased from 1.4 mil in 2001 to 1.2 mil in
2010

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HIV trends in sub-Saharan Africa:
Number of PLHIV increased from 20.5 mil in 2001 to 22.9 mil in
2010

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HIV/AIDS in Ethiopia

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Historical Overview of HIV/AIDS in
Ethiopia
• The first evidence of HIV infection in Ethiopia in 1984
• A National HIV/AIDS Taskforce was established in 1985
• The first two AIDS cases reported to the Ministry of Health in 1986
• The National AIDS Control Program (NACP) was established by the
MOH in 1987.

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 The National Status

• HIV positive pediatric population

• Estimated 79,871 for 2010
• Represent 6.6% of estimated PLHIV in Ethiopia
• National AIDS related pediatric deaths
• Estimated 3,537 annually
• Represent 12.6% of the estimated total deaths
• New HIV infection in children
• Estimated 14,276 in 2010
• Represent 10.4% of total new infections
Source: FHAPCO SPE (2010) 18
 Cont..

• Pediatric clients ever enrolled

• As of Feb 2010, a total of 29,546 children are ever enrolled

• Represent 6.7% of national total
• That is 37% of estimated HIV positive children
• Estimated 26,053 children were eligible to start ART by 2010

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 National Pediatric ART…
• Out of estimated 26,053 ART eligible children, a total of 13,650
children were ever started (end of Feb, 10)
• Represent 5.5% of the national total

• It means 52.4% of estimated eligible children

• A total of 10,496 children were actively on ART at the end of Feb 2010
(77% of ever started)

Source: FHAPCO HIV Care and ART Update (Feb 2010)

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• DHS 2011 data show an overall prevalence of 1.5% among
the general population. (15 – 45years)
• Among women age 15-49 HIV prevalence is 1.9 percent, and
among men age 15-49, prevalence is 1.0 percent
• 789,900 people currently living with HIV/AIDS
• 607,700 adults
• 182,200 children aged 0-14 years (23%)
• 952,700 AIDS orphans.

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• The disease more prevalent in urban areas. Nonetheless,
synthesis of epidemiological data also indicates that while
the epidemic has stabilized and declining in most of urban
areas,
• The rate of new HIV infections seems to be increasing in
smaller towns.

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Origin of HIV

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Q. The origin of HIV-1 is thought be:
a. A biological weapon manufactured by the developed
world
b. Recombination with other human retroviruses such as
XMRV and HTLV-I
c. Repeated exposure to mosquito bites
d. Vaccines that got contaminated with monkey cells
e. Zoonotic transfer of a simian (chimpanzee lentivirus) to
humans, likely by percutaneous inoculation.
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ORIGINS OF HIV
• Molecular clock analyses place last common ancestor of the HIV-1 M
group prior to 1940. Jump from chimpanzees to humans occurred
before then
• Bushmeat hypothesis – it is likely that HIV-1 spread to humans by parenteral
inoculation of SIVcpz, perhaps during hunting/butchering, in West Africa, in
southeastern Cameroon, about 100 years ago or so.
• HIV-1 and HIV-2 have each arisen several times
• In the case of HIV-1, the four groups (M, N, O and most recently, P) are the
result of independent cross-species transmission events from
chimpanzees.
• The M or Main group is the lentivirus that has spread world-wide

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HIV-1 Dynamics
• Approximately 10 billion (1010) particles of HIV-1 are produced and
cleared daily in an infected individual
• Generation time approx 2 days
• 2 billion CD4+ lymphocytes destroyed each day
• The entire supply of CD4 cells turns over approximately every 15 days

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 Classification of HIV
• HIVs are members of the Retroviridae family and belong to the Lentivirus
genus
• Retrovirus family:
• Single stranded RNA transcribed to double stranded DNA by reverse transcriptase
(Reverse transcription into double-stranded cDNA)
• Integrates into host genome
• High potential for genetic diversity
• Can lie dormant within a cell for many years, especially in resting (memory) CD4+ T4
lymphocytes
• HIV type (distinguished genetically)
• HIV-1
• HIV-2

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• HIV-1
• Worldwide pandemic
• Ancestrally derived from a chimpanzee lentivirus called SIVcpz,
accessory gene is vpu
• Globally, the vast majority of HIV cases are caused by HIV-1

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HIV-2
• Quite different from HIV-1 genetically, 40-60% amino acid sequence homology
with HIV-1
• Identical mode of transmission but less transmissible
• If disease occurs, identical clinical picture to disease caused by HIV-1 (but much
lower rate of disease progression)
• Derived from a lentivirus of sooty mangabeys (SIVsm), accessory gene is vpx
(The major difference between the genomes of HIV-1 and HIV-2 is the fact
that HIV-2 lacks the vpu gene and has a vpx gene not contained in HIV-1)
• Found predominantly in West Africa and Western India
• Subtypes A and B are the major causes of infection in humans but rarely cause
infection in children
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How many subtypes of HIV-1 are there?
• The strains of HIV-1 can be classified into four groups:
• The "major" group M,
• The "outlier" group O and
• Two new groups, N and P

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• Group O exhibits about 0.4% prevalence in Cameroon
• Group N is exceedingly rare, with less than 10 infected individuals
identified to date, and
• Group P infections are also extremely rare, accounting for only 0.06%
of HIV infections

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• More than 90 percent of HIV-1 infections belong to HIV-1 group M
• Within group M there are known to be at least nine genetically distinct
subtypes (or clades) of HIV-1. These are subtypes A, B, C, D, F, G, H, J
and K
• Occasionally, two viruses of different subtypes can meet in the cell of
an infected person and mix together their genetic material to create a
new hybrid virus (a process similar to sexual reproduction, and
sometimes called "viral sex").
• Many of these new strains do not survive for long, but those that infect
more than one person are known as "circulating recombinant forms" or
CRFs. For example, the CRF A/B is a mixture of subtypes A and B
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Where are the different subtypes and CRFs
found?
• Subtype A and CRF A/G predominate in West and Central Africa, with
subtype A possibly also causing much of the Russian epidemic.9
• Subtype B has been the most common subtype/CRF in Europe, the
Americas, Japan and Australia
• Subtype C is predominant in Southern and East Africa, including
Ethiopia, India and Nepal.
• It has caused the world's worst HIV epidemics and is responsible for around
half of all infections.
• Subtype D is generally limited to East and Central Africa.

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Cont…
• CRF A/E is prevalent in South-East Asia, but originated in Central
Africa.
• Subtype F has been found in Central Africa, South America and
Eastern Europe.
• Subtype G and CRF A/G have been observed in West and East Africa
and Central Europe.
• Subtype H has only been found in Central Africa;
• J only in Central America; and
• K only in the Democratic Republic of Congo and Cameroon

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The structure of HIV
What does HIV look like?
• Like other retroviruses, HIV-1 is an enveloped virus
• Outside of a human cell, HIV exists as roughly spherical particles (sometimes
called virions).
• The surface of each particle is studded with lots of little spikes
• An HIV particle is around 100-150 billionths of a metre in diameter. That's about
the same as:
• 0.1 microns
• 4 millionths of an inch
• one twentieth of the length of an E. coli bacterium
• one seventieth of the diameter of a human CD4+ white blood cell.
• Unlike most bacteria, HIV particles are much too small to be seen through an
ordinary microscope. However they can be seen clearly with an electron
microscope 36
• The HIV envelope is a lipid bilayer that was acquired from the host cell
plasma membrane as the virus budded through the cell membrane
• There are two major glycoproteins associated with the HIV envelope,
gp120 and gp 41
• gp120 forms knob of the envelope structure
• gp41, a transmembrane protein anchored in the viral lipid bilayer, forms the
stalk of the envelope structure
• The nucleocapsid core contains the HIV genome and viral enzymes
including reverse transcriptase, integrase, and protease enzymes as
well as other proteins with structural and regulatory functions

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How many genes does HIV have?
• HIV has just nine genes encoding 15 different proteins
• Three of the HIV genes (gag, pol and env) contain information needed
to make structural proteins for new virus particles.
• Gag encodes the main structural proteins including matrix, capsid, and
nucleocapsid
• Pol encodes enzymes such as reverse transcriptase, protease, and integrase
• Env encodes the envelope glycoproteins gp41 and gp120

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• The other six genes (tat, rev, nef, vif, vpr and vpu) code for proteins
that control the ability of HIV to infect a cell, produce new copies of
virus, or cause disease
These genes have a variety of functions including regulatory, infectivity,
virulence, replication, and virus release
• At either end of each strand of RNA is a sequence called the long
terminal repeat, which helps to control HIV replication

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p24
p17 Matrix – p17

P7, P6

kb 9.7 41
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Life Cycle of HIV

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• Binding of gp120 to CD4 and co-receptor on the cell surface
• Fusion of the viral envelope with the cell membrane
• Release and disassembly of the viral core in the cytoplasm
• Reverse transcription (Reverse transcriptase enzyme translates HIV’s
single stranded RNA into a provirus made of double stranded DNA)
• Viral DNA moves into cell nucleus
• Viral DNA is integrated (by Integrase enzyme) into host genome to
form HIV provirus
• HIV provirus DNA is transcribed back to both viral genomic RNA and
viral mRNA , the latter which is translated to HIV polyproteins.
• The RNA virus and polyproteins are assembled beneath the cell
membrane
• The assembled package becomes enveloped in the host cell membrane
as it buds off to form an HIV virion.
• Further assembly and maturation occurs outside the cell by the protease
enzyme, rendering the HIV virion infectious. 46
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 HIV-1 ENTRY
• HIV cell entry occurs in three stages
• The first step of the HIV life cycle is binding to specific receptors on
the cell surface, primarily CD4 receptor. This step is known as
attachment
• The envelope protein gp120 binds to the CD4 receptor.
• Attachment by itself was found not to be sufficient for HIV entry. This led to
the concept of a second receptor (co-receptor)
• Expression cloning approach led to the discovery of 2 main co-receptors, the
chemokine receptors CXCR4 and CCR5

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• The second step of the HIV life cycle is coreceptor binding
• When the HIV glycoprotein gp120 binds to the CD4 receptor during
attachment, it induces a conformational change in gp120 that exposes the
coreceptor binding site
• This exposure of the coreceptor binding site allows binding of gp120 to the
coreceptor
• Coreceptor binding triggers conformational changes in gp41

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• The third step of the HIV life cycle is known as fusion.
• Conformational changes in gp41 leads to the insertion of a fusion peptide into
the target cell membrane, resulting in fusion between the cell and viral
membranes
• Fusion allows the nucleocapsid, which contains the viral RNA genome and
enzymes to enter the cytoplasm of the cell

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 HIV-1 REVERSE TRANSCRIPTION
• After entry, the virus uncoats and reverse transcription takes place
• The HIV reverse transcriptase is an RNA-dependent DNA polymerase.
• During reverse transcription, a double-stranded DNA copy of the
single-stranded genomic RNA is made
• Reverse transcriptase does not have proof-reading capability. Thus,
replication is error-prone resulting in the introduction of point
mutations into each new copy of the viral DNA

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 INTEGRATION
• The integration of HIV-1 proviral DNA into the host cell genome is an
obligate replication step of the HIV life cycle.
• Integration is catalyzed by the viral integrase and occurs in three main
steps through a series of DNA cutting and joining reactions:
• A dinucleotide is removed from each 3'-end of the viral DNA, a process
termed 3'-end processing.
• The resulting three-prime ends are joined to the 5’ ends of the chromosome
DNA, at a staggered distance about 5 nucleotides apart. This step is called
DNA strand transfer
• Unknown host cell enzymes repair the gap in the DNA chain by removing the
two unpaired nucleotides at the 5'-ends of the viral DNA

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 Integration allows HIV-1 to:
• Establish a permanent reservoir.
• Evade immune surveillance.
• Rebound if HAART is withdrawn (latency in resting memory T cells).
• ARCHIVE drug resistance mutations - serious clinical problem.
• Replicate through mitosis.
• In a patient on long-term HAART, the most stable reservoir of
integrated proviruses is in rare resting memory T cells (roughly one
million persist in the body of a patient with effective HAART).
• The half life of this reservoir is decades, meaning that HAART cannot
be curative.
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 Assembly and Budding (Protease
Cleavage)
• Following integration, immune activation leads to transcription of the
viral genome into viral subunits which are then exported to the
cytoplasm for translation into viral proteins
• These viral proteins included genomic RNA as well as structural,
enzymatic, and regulatory proteins
• Among the viral proteins produced are Gag and Gag-Pol precursor
polypeptides that are cleaved into their smaller functional
components by the HIV-1 protease.
• The genomic RNA and viral proteins are packaged into a virion. The
mature virion is released from the cell surface in a process called
budding
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Mechanisms used by HIV-1 to evade immune responses

• Mutations no longer recognized by cytotoxic T lymphocytes (CTL escape

mutations)
• Mutations no longer recognized by neutralizing antibodies (neutralizing
antibody escape mutations)
• Inherent resistance to neutralization
• Downregulation of MCH class I expression (mediated by viral gene
products, e.g. Nef, acting within the infected cell)
• Preferential infection and destruction of HIV-1-specific CD4+ T
lymphocytes
• Dysregulation of cytokine production (IL-2, IFN-, IL-12, IL-10)
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Tissues where HIV replicates
• Lymph nodes
• Spleen
• Bone marrow
• Gut associated lymphoid tissue (GALT)
• Brain
• Testis

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Life Span of HIV and Infected cells
• 109 - 1011 viral copies per day
• Average life-span of HIV in plasma is 30-60mins
• Average life-span of HIV-infected CD4 lymphocytes is ~1.6 days
• Integrated HIV genome can stay dormant within a cellular DNA for
many years
• Cellular activation plays an important role in the replication cycle of
HIV (e.g., TB)

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Pathogenesis of HIV

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Other Target Cells of HIV
• Numerous organ systems are infected by HIV:
• Brain: macrophages and glial cells
• Lymph nodes and thymus: lymphocytes and dendritic cells
• Blood, semen, vaginal fluids: macrophages
• Bone marrow: lymphocytes
• Skin: langerhans cells
• Colon, duodenum, rectum: chromaffin cells
• Lung: alveolar macrophages

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HIV in Children
• HIV during infancy = primary infection
• Acquisition of HIV can occur in utero, intrapartum, postnatally (through breast feeding)
• Very high viral load: peak at 6-12 weeks of life
• Multiple factors influence rate of disease progression:
• Maternal advanced disease
• Maternal vital status
• Timing of transmission (intrapartum vs peripartum vs. late)
• Genetic susceptibility
• Virus characteristics
• Likelihood of disease progression is associated with child’s CD4 count and HIV-1
RNA copy number

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Mode of Transmission

 MTCT accounts for > 95% of pediatric HIV infection in sub-Saharan

Africa, including Ethiopia

 Evidences show that elimination of pediatric HIV infection is a

possibility

 UNAIDS has called for virtual elimination of pediatric HIV infection,

defined as MTCT risk of < 5% by 2015.

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 Timing and Rates of Transmission
Time of Transmission Transmission
Rate
During Pregnancy 5-10

During labor and delivery 10-20

During breast feeding 5-20

Overall without breast feeding 15-30

Overall with breast feeding through 6 months 25-35

Overall with breast feeding through 18-24 months 30-45

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 Approaches to prevent MTCT
• The 4 prongs of PMTCT:

Prong 1: Primary prevention of HIV infection

Prong 2: Preventing unintended pregnancy among HIV
infected women
Prong 3: Prevention of MTCT of HIV in a pregnant
woman
Prong 4: Providing care and support to HIV- infected
women, their infants and their families

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Prong 1: Primary prevention
• Communication for behavior change (ABC approach) to protect men and
women of childbearing age from becoming infected with HIV and other
STIs
• HIV testing and counseling services following the national guidelines
• Correct and consistent use of condoms
• Open discussion on reproductive health (RH) issues between parents and
their children
• Early diagnosis and treatment of STIs
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Prong 2: Prevent unintended pregnancy
• Estimates of unintended pregnancies as high as 51-
91% in Africa
• Family planning counseling integrated into all
potential PMTCT and HTC service sites
• Dual protection with condom use
• Reproductive rights of women with HIV

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Prong 3: Prevent MTCT
Option B+

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How effective are PMTCT regimens?

• Single dose NVP has been shown to reduce MTCT by 50 % in Africa

• Maternal HAART: to < 2% when VL is > 1000 copies/ml at delivery
and to < 1% if VL is < 1000 copies/ml at delivery
• WHO believes that wide scale implementation of the new 2010
PMTCT recommendations can reduce the risk of MTCT to < 5% in
breast feeding populations and to < 2% in non-breast feeding
populations

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Access to HIV prohylaxis
• “ It is unacceptable that 98% of pregnant women in
developed countries are able to access HIV
prophylaxis to stop transmission to their babies when
little more than 33% in developing countries can do
so.”

Michel Sidibe, ED of UNAIDS

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Prong 4: Provide Care & Support

 Components of Care of HIV Exposed Infants:

• History taking
• Physical examination
• Growth assessment
• Developmental assessment
• Immunization
• CPT
• Determination of infection status

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Other modes of HIV transmission in children

• Horizontally transmitted HIV in children accounts for < 5% of

pediatric HIV infection
• Sexual abuse
• Unsafe injections
• Transfusion from HIV infected blood products
• Wet nursing by untested woman
• Manipulation by local healer (uvula cutting, milk teeth extraction,
tonsillectomy)
• Feeding children by chewed food by the mother / adult care taker
• using sharp object contaminated with HIV infected blood
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Disease Progression in Children
• Disease progression is much more rapid in children than in
adults because:
• Children’s immune system is immature and still developing
• Infants have more CD4 cells, which allow more targets for
the HIV virus
• Vertically infected children have three patterns of disease
progression
• 10-25% are rapid progressors. Rapidly progress to AIDS
and die with in the first year of life (6 – 9mo)
• Majority (50 – 60%) have slower progression to AIDS with
a mean-time of 3 to 8 years
• 5 - 15% are long-term non-progressors may not exhibit
symptoms for > 8 years

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Immunological Differences in Children

• CD4 count is much higher in children

• In the first year of life the absolute CD4 count is more than 3 times than in
adults
• This gradually decreases to adult level by age 6
• Adult Immunological Staging cannot be used in young children
• Immature immune system makes children more vulnerable to minor and invasive
bacterial pathogens
• Immune systems in younger children may have a greater capacity to reconstitute
than adults
• Children usually have a good immunological response to ART

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Viral Load Differences in Children

• Adults with acute HIV infection have high viral loads that rapidly decline over a
few weeks to a “set point” within 6 months of infection
• Children have extremely high levels of plasma virus during the first year of life
• This level declines more slowly over several years; their set point is achieved
much later than adults

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Viral Load in Adults Viral Load in Infants

Plasma HIV RNA levels in Adults

Plasma HIV RNA levels in Infants
1000000
Viral load no.copies/mL (log)

10000

100

1
1 2 3 4 years 1 2 3 1 2 years 2 2.5 3 4
Months/Years Months/Years
Peak: 300,000
Peak 1000,000

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Components of Clinical Care
for the HIV-Exposed Infant
• History (birth, interim history, and parental concerns)
• Physical exam
• Growth and nutrition evaluation
• Developmental assessment
• Cotrimoxazole preventive therapy
• TB screening
• Routine immunizations
• Determination & evaluation of infection status
• Assessment and plan

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Signs Highly Suggestive of HIV Infection
in Infants

Oral thrush Hepatosplenomegaly

Growth failure
Extensive Molluscum 77
Failure-to-Thrive
• The failure to sustain a normal velocity of weight and/or height
growth during the first 3 years of life – downward crossing of 2
percentiles over time
• Can be quantified using growth curves
• May be indication:
• Of HIV disease in exposed infant
• For ARV treatment in infected infant/child
• Of ARV treatment failure in child on therapy

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Developmental Assessment
• Delayed/abnormal development or loss of milestones may
be the first sign of HIV infection in infants that raise concerns

• Abnormal development can be caused by other factors

• Infants are at high risk for HIV encephalopathy

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Developmental Assessment
• Development is assessed by Hx, observation of the child and
neurologic examination

• Milestones achieved in the past

• When did the child show social smile, support his head, sit with (out)
support, crawl, walk, language development etc.

• Currently what is he able to do?

• Use developmental checklist to be systematic.

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 Red Flags!
Age Warning Signs
1 month Does not regard face, no eye contact, no smile, poor suck, floppy
2 months Does not look at you with both eyes at least for a few moments, and does
not follow with eyes if you move your face slowly from side to side
3months Does not respond to sound by quieting, absence of social smile
4months Does not hold head steady for a few moments when you sit him up, does
not grasp rattle that you put into his palm
5months Does not raise head and support weight on arms when in prone position
6 months Cannot reach for objects with both hands, Floppy, no response to sound,
Poor social response to people
9 months Unable to sit unsupported , hand preference, fisting, persistence of
primitive reflexes
12months Unable to bear weight on legs
15 months Does not walk alone, is not using at least one word meaningfully
18 months Does not use at least 3 words, and does not point to what he wants 81
Co-trimoxazole Preventive Therapy
• All HIV-exposed infants until infection is ruled out

• All HIV infected infants 1-12 months regardless of clinical

stage or CD4 count

• PCP prophylaxis for HIV-exposed infants

– Until the child is no longer breast-feeding and is determined to be
uninfected either by DNA PCR or Rapid HIV antibody test based on
the national infant HIV diagnosis algorithm
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Determining Infection Status
• Priority to determine infected babies who need care and treatment
rather than confirm the absence of disease
• All HIV exposed infants should have virologic testing early, between 6-
8 weeks of age
• Interpretation should be done in the context of the clinical
presentation of the infant
• Antibody test is used in children 18 months of age
• If virologic tests are not available, WHO recommends presumptive
clinical diagnosis of severe HIV in infants <18 months of age
• Breastfed infants with initial negative virologic tests should continue
to be evaluated for clinical evidence of HIV infection 83
 HIV Testing in HIV-exposed Infants <12 months Where
Virologic Testing is Available

HIV Exposed Infant

DNA PCR at 6 weeks or at earliest opportunity after age 6 weeks

Start co-trimoxazole prophylaxis.

Positive Negative

HIV Infected
Initiate HAART
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 PCR Negative at 6 Weeks

Continue follow-up per national guidelines;

continue co-trimoxazole

Infant or child remains

If infant or child gets sick well
Repeat DNA PCR Continue follow-up;
Continue co-trimoxazole Continue co-trimoxazole

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 Gets sick… Remains well…

Continue follow-up;
Repeat DNA PCR;
Continue co-trimoxazole Continue co-trimoxazole
Rapid test at  12 mos
Positive Negative
Positive Negative Repeat DNA Not HIV
PCR infected

Initiate HIV infection unlikely Positive

Follow-up in
HAART Look for other causes;
routine child
Rapid test at  12 mo
and  6 wks after Assess for HAART care services
complete cessation of eligibility
breast feeding
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Infant / child diagnosis
• HIV DNA PCR at 4-6 weeks
• Identifies >95% of HIV positive infants
• HIV antibody tests at 9-18 months
• Will identify exposed infants
• Will confirm HIV negative if not breastfeeding within last 3
months
• HIV antibody tests ≥ 18 months confirm HIV infection if
positive

87
 Antibody versus virological tests
Antibodies tests, including rapid test Virological assays such as RNA or DNA PCR

Directly detect the presence of the HIV virus or

Detect antibodies made by immune cells in products of the virus in the blood
response to the virus
Antibodies from the mother pass on to child and Positive virological test can therefore reliably
most have gone by 12 months of age, but in detect HIV infection at any age, even before the
some instances they do not disappear until the child is 18 months old
child is 18months of age

A positive antibody test in children under the If the tests are negative and the child has been
age of 18 months is not a reliable way to check breast-feeding, this does not rule out infection
for infection of the child → Tests done six weeks or more after completely
stopping breast feeding

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 Care of HIV Infected Infants & Children
Components of routine care for HIV infected infants and
children:
1. History (past, interim, parental concerns)
2. Nutrition evaluation
3. Developmental assessment
4. Physical examination
5. Laboratory evaluation
6. Staging/classification
7. Preventing Opportunistic infections
8. TB screening
9. ARV eligibility
10. Assessment & plan
11. Follow up schedule 89
Recommended Lab Evaluations
A. CD4 monitoring
• CD4 should be measured at baseline F/U or prior to initiating ART
and every 6 mo then after.
• Monitor with increasing frequency as CD4 approaches the
threshold for starting ART
• Measure CD4 if new clinical staging events develop (growth
faltering, neurodevelopmental delay, etc)

90
Laboratory Evaluation
• Which Laboratory Tests Need To Be Done?
• Complete Blood Count
• CXR if clinically indicated
• CD4 Count
• Pregnancy test for sexually active adolescent females
• CD4 number and percent
• When infant is determined to be HIV-infected
• Upon enrollment for older children
• Every six months there after

91
Why use CD4 percentage in Children?
• CD4 counts and percentages in healthy infants are very high at birth and during
the first year of life and then decline
• The absolute CD4 count varies a lot during the first year of life and is more than 3
times that of adults
• CD4% is a more stable value than absolute number, so percentage is preferred in
children under 5 years of age
• Because of these differences, adult values do not apply in children below the age
5 years
• CD4 count of 500 is considered okay for a 7 year old but is severe suppression for a 6 month
old

92
Viral Load Monitoring
• VL determination is desirable, but not essential prior to initiating ART

• VL should be assessed to confirm clinical or immunological failure

where possible, prior to switching regimen

NB: The inability to perform lab monitoring, notably for CD4 or viral
load should not prevent children from receiving ART

93
Preventing Opportunistic Infections
• Occurs with severe immune suppression
• Young children have primary infection rather than reactivation as in
adults
• Immature immune system of the infant leads to more fulminant
course than in adults
• Prophylaxis prevents disease progression and morbidity and
mortality!

94
Co-trimoxazole preventive therapy
• CPT in ALL HIV INFECTED INFANTS significantly reduces the rate
of PCP and other bacterial infections
• Indications for CPT include:
• All HIV infected children < 12 months regardless of CD4 or clinical status
• All HIV infected children 1-4 years of age with:
• WHO stage 2, 3 or 4 diseases regardless of CD4 count.
• CD4 percentage < 25%
• All HIV infected children with prior PCP
• Children <18 months of age with presumptive diagnosis of severe HIV disease
• All HIV infected Children > 5 years should start or continue
• Clinical stage 2, 3 and 4 disease
• CD4 count <350
95
TUBERCULOSIS AND HIV CO-INFECTION IN CHILDREN

• One third of the world population is infected with tuberculosis.

• Higher risk of progression from latent to TB disease compared with adults –
• 50% progression in those less than 1 year old
• 10 – 20% between 1 – 2 years and
• 5% between 2 – 5 years of age
• 11- 48% of children with TB in resource limited settings are co-infected with
HIV.
• HIV-infected children have a six times greater risk of dying from TB
• Children are infected by an adult with open case of tuberculosis through
inhalation of the bacilli

96
Tuberculosis Screening
• TB is the most common opportunistic infection among HIV-infected patients in
Africa, SE Asia
• Leading cause of AIDS-related deaths worldwide: 1/3 of all AIDS-related deaths
are due to TB
• High rates of co-infection (HIV and TB)
• Can be prevented by:
• Treatment of latent TB infection (INH preventive therapy- IPT)
• Use of antiretroviral therapy
 Infants and children living with HIV should routinely be screened for TB as a part
of standard clinical care, whether they are receiving TB prophylaxis or ART.
 Hx of contact with TB patient (regardless of type of TB) is important
97
Tuberculosis Screening: Special Issues for
Children
• TB is difficult to diagnose in children
• Limited yield of diagnostic procedures:
• Poor sputum production
• Low yield of gastric aspiration
• Sputum induction and bronchoscopy not routinely used
• Multiple varied clinical manifestations
• Overlap with other HIV disease manifestations
• BCG vaccination results in false positive Tuberculin Skin Testing (TST)
• Limited sensitivity of TST in HIV-infected children
• Associated with severe complications
• Meningitis
• Miliary TB
98
Pediatric TB screening algorithm-Infant

Infant with Hx of contact with TB case

No Yes

Not eligible for IPT Well Symptomatic

Give IPT if no
Refer/work-up for TB
contraindications
99
 Work-up for TB

Active TB No active TB

Treat for common childhood

Treat for tuberculosis
illnesses

Further work-up if not

Give IPT if infant improved
improved

Screen for TB at every visit 100

 HIV infected child > 12 months

Screen for TB with any one of the following

Poor weight gain

Fever
Current cough
Contact Hx with TB patient

Negative screening Positive screening

Assess for CI for IPT Work-up for TB

101
 Give IPT if no CI
Active TB diagnosed?
 Defer IPT if CI

Yes No

Treat for TB Treat for common childhood

illnesses

Give IPT if child Further work-up if not

improved improved

Screen for TB at each visit

102
Approach to management of TB/HIV co – infection
Overlapping toxicities
Side Effects Anti-TB Drugs ARV Drugs

Skin rash PZA, RMP, INH NVP, EFV,ABC

Nausea, vomiting ETH, EMB, PZA, RMP, INH AZT, RTV, Kaletra

Hepatitis PZA, RMP, INH, ETH NVP, EFV, all PIs

Leukopenia, anemia INH, RMP AZT

Peripheral neuropathy INH d4T, ddI

Always add vit B-6 supplementation

103
HIV-infected children who develop TB while on ART

• For all HIV-infected children, anti-TB therapy should be started

immediately upon the diagnosis of TB; ART should continue
• Make adjustments to ART regimens as needed to decrease the
potential for toxicities and drug interactions:
• If on a regimen of 2 NRTIs + NVP, substitute EFV for NVP if child is 3 years
of age and above
• If on a regimen of 2 NRTIs + NVP and substitution with EFV is not possible,
ensure NVP is dosed at the maximum dose of 200 mg/m2 per dose twice daily
• If on a regimen of LPV/r, consider adding RTV to a 1:1 ratio of LPV: RTV to
achieve the full therapeutic dose of LPV

104
INH prophylaxis in infants and children (IPT)

• IPT should be administered after excluding active TB

• All HIV-infected infants and children exposed to TB through
household contacts, but with no evidence of active disease
• Children living with HIV (older than 12 months of age and including
those previously treated for TB), who are unlikely to have active
TB, and are not known to be exposed to TB
• HIV positives who are Children less than 12 months of age who are
HIV +ve who have contact with a TB case
• All children living with HIV who have successfully completed
treatment for TB disease should receive INH for an additional six
months
105
Clinical and Immunological Staging
Immunologic Staging
 In children younger than 5 years of age, CD4 percentage is
preferred for monitoring immune status (age related changes)
 Measure CD4 values when patients are clinically stable
 Any child with severe immune suppression is eligible for ART
independent of WHO stage

106
Revised WHO Clinical Staging of HIV/AIDS for Infants and
Children
Stage 1:
• Asymptomatic
• Persistent generalized lymphadenopathy
WHO Clinical Stage 2
• Unexplained persistent hepatosplenomegaly
• Papular pruritic eruptions
• Extensive wart virus infection
• Fungal nail infections
• Angular cheilitis
• Lineal gingival erythema (LGE)
• Extensive molluscum contagiosum
• Recurrent oral ulcerations
• Unexplained persistent parotid enlargement
• Herpes Zoster
• Recurrent or chronic URTIs (otitis media, otorrhoea, sinusitis, tonsillitis)
 WHO Clinical Stage 3
• Unexplained moderate malnutrition or wasting not adequately responding to standard
therapy
• Unexplained persistent diarrhoea (14 days or more)
• Unexplained persistent fever (above 37.5°C, intermittent or constant, for longer than
one month)
• Persistent oral candidiasis (after first 6-8 weeks of life)
• Oral hairy leukoplakia
• Acute necrotizing ulcerative gingivitis or periodontitis
• Tuberculosis (Lymph node and Pulmonary)
• Severe recurrent bacterial pneumonia
• Symptomatic lymphoid interstitial pneumonitis (LIP)
• Chronic HIV-associated lung disease including brochiectasis
• Unexplained anaemia (<8g/dl), neutropenia (<0.5 x 109/L) and/or chronic
thrombocytopenia (<50 x 109/L)
 WHO Clinical Stage 4
• Unexplained severe wasting, stunting or severe malnutrition not
responding to standard therapy
• Pneumocystis pneumonia
• Recurrent severe bacterial infection (e.g. empyema, pyomyositis, bone or
joint infection, meningitis, but excluding pneumonia)
• Chronic herpes simplex infection (orolabial or cutaneous for > 1 month
or visceral at any site)
• Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
• Extrapulmonary TB
• Kaposi sarcoma
WHO Clinical Stage 4
• CMV infection; retinitis or CMV affecting another organ, with onset at age older than 1
month
• CNS toxoplasmosis (after the neonatal period)
• Extrapulmonary cryptococcosis (including meningitis)
• HIV encephalopathy
• Disseminated endemic mycosis (coccidiomycosis, histoplasmosis)
• Disseminated non-tuberculous mycobacterial infection
• Chronic cryptosporidiosis (with diarrhoea)
• Chronic isosporiasis
• Cerebral or B cell non-Hodgkin lymphoma
• Progressive multifocal leukoencephalopathy (PML)
• Symptomatic HIV associated nephropathy or HIV-associated cardiomyopathy
HAPPY EASTER!

112
Clinical criteria for presumptive diagnosis of severe
HIV disease in infants and children <18 months of age
• A presumptive diagnosis of severe HIV disease should be made if:
 The infant is confirmed HIV antibody positive; and
 Diagnosis of any AIDS-indicator condition(s) can be made; or
 The infant is symptomatic with two or more of the following:
o Oral thrush
o Severe pneumonia
o Severe sepsis
Other factors that support the diagnosis of severe HIV disease in an HIV
seropositive infant include:
 Recent HIV-related maternal death
 Advanced HIV disease in the mother
 CD4 <20% in infant
* Confirmation of the diagnosis of HIV infection should be sought as soon as
possible 113
Steps to ART Initiation

• Confirm diagnosis
• Clinical evaluation (Clinical staging)
• Immunologic evaluation (immunological staging)
• Then determine eligibility
• Base line laboratory investigations
• CBC,LFT,RFT
• Assess family readiness
• Choose appropriate drug regimen
Process of Initiating ART

 Complete clinical assessment( including G&D)

 Insure medical criteria are met and no medical contra indications to ART,TB
excluded.
 Screen for and treat any inter-current or opportunistic infection
 Baseline laboratory assessment
 Assess patient’s and/or care givers readiness (adherence counseling)
 Consider disclosure issues depending on age and maturity
 Ensure access to nutrition and OI prophylaxis

115
Ethiopian Guideline for Starting ART in Infants &
Children
Age of the child
WHO
Availability of
Pediatric Age <12
CD4 cell assay >12 months
Stage months

CD4
4 Treat All
No CD4
CD4 Treat all except those with TB, LIP,OHL,
thrombocytopenia, and take into account CD4
3 No CD4 value
Treat all
CD4 CD4 guided
2 No CD4 TLC -guided
CD4 CD4 guided
1 No CD4 Do not treat
 Immunological criteria for starting HAART

Infants 12-35 months 36-59 months

Age < 12 months > 5 years

CD4% <20 <20 <15

All

Absolute CD4 <750 cells/ mm3 <350 cells/ mm3 < 200
WHO criteria for Starting ART in Infants &
Children/2010 revised
Age of the child
Availability
WHO
of
Pediatric Age <24
CD4 cell >24 months
Stage months
assay

CD4
4
No CD4
CD4 Treat All

3 No CD4
Treat all
CD4 CD4 guided
2 No CD4 TLC -guided
CD4 CD4 guided
1 No CD4 Do not treat
 Revised WHO Immunological criteria for starting HAART

Infants 24-59 months

Age < 24 months > 5 years

CD4% <25 <15

All

Absolute CD4 <750 cells/ mm3 < 350

When to start (National GL)
 All HIV exposed infants < 12months of age testing HIV positive by DNA PCR
regardless of stage and CD4 count
 HIV exposed infant <18 months meeting the WHO criteria for presumptive severe
HIV disease in the absence of virologic test
 Children with WHO Stage IV
 Children with WHO stage III
 Children with WHO Stages I and II should only initiate ART if they have evidence
of severe immune suppression
 Children with severe immune suppression independent of WHO stage

120
When to start ART in children (WHO 2010
recommendations)
• Infants and children < 24 months:
• All HIV infected infants and children < 24 months of age irrespective of stage
• Infants and children < 18 months with a diagnosis of presumptive severe HIV
disease
• Children 24 months and older:
• Clinical and immunological threshold should be used
• All HIV infected children  24 months with WHO stage 3 and 4 irrespective
of CD4

121
Reasons for Deferring Therapy

• Eligibility
• Intercurrent infections
• Medical problems e.g. anemia, renal, hepatic impairment, concurrent therapy
such as rifampicin
• Terminal illness
• Readiness
• No caregiver
• Serious adherence concerns
 Antiretroviral Medicines Available for Children

NRTI NNRTI PI
Stavudine(d4T)* Nevirapine(NVP)* Lopinavir/ritonavir
Zidovudine (AZT)* Efavirenz(EFV)* (LPV/r)*(Kaletra)
Lamivudine (3TC)* Ritonavir(RTV)*
Emtricitabine (FTC) Nelfinavir(NFV)*
Didanosine (ddI)* Indinavir(IDV)
Abacavir (ABC)* Atazonavir

* Available in paediatric formulation

New ARV drugs

• Fusion inhibitors– Enfuvirtide
• Integrase inhibitor – Raltegravir
• CCR5 Blockers - Maraviroc
Medical contra-indications
• Severe Anemia (Hb<6.9 gdl) Contraindication to AZT, replace with d4T
• Severe Neutropenia (ANC<250 mm3) AZT use requires close monitoring. Can
substitute d4T if ANC falls
• Severe Renal Insufficiency (Creatinine > 3 times normal) Contraindication to
ARV use. Patient not eligible for ART
• Severe Hepatic Insufficiency (LFTs > 5 times normal) Contraindication to NVP
use. Use EFV in children older than 3, PI treatment suggested for small children
• History of prior ARV use Potential for ARV resistance. Consult for expert
management
• Current use of rifampin containing TB regimen- Interactions with NVP. If CD4 is
high, consider deferring ART or use ritonavir containing regimen for children
under 3 and EFV containing regimen for children older than 3
124
Preferred first line regimens
Children < 3 years Children  3 years

ZDV + 3TC + NVP ZDV + 3TC + NVP/EFV

or or
ABC+3TC+NVP ABC + 3TC + NVP/ EFV
or or
D4T+3TC+NVP D4T+3TC+NVP/EFV

Infants up to 24 months with history of PMTCT or NNRTI exposure

AZT + 3TC + Kaletra Or NB: NVP based therapy should be

used when Kaletra is not available
ABC+3TC+Kaletra Or

d4T +3TC + Kaletra

125
First line regimens in specific situations
Situation Regimen

Severe anemia NVP + 2NRTIs (avoid AZT)

< 3 yrs with TB PI + 2NRTI or

treatment 3NRTIs (AZT-3TC-ABC or d4T-3TC-ABC)

> 3 yrs with TB EFV + 2NRTI or

treatment 3NRTI (AZT-3TC-ABC or d4T-3TC-ABC)

Adolescents with TDF + (FTC or 3TC) + NNRTI

hepatitis B

126
Preferred 2nd line regimens
Preferred second line regimen

First line regimen at failure RTI components (NRT PI component

or NNRTI)

2NRTI + 1 NNRTI ABC + 3TC or LPV/r

AZT or d4T containing ABC + ddI
PLUS

ABC containing AZT +3TC or

AZT +ddI
LPV/r
Triple NRTI ddI + EFV or NVP

127
Pediatric ART: Important Principles

• Dosage is by weight – child must be weighed at each clinic visit and dosage
checked with new weight
• Change to tablets or capsules whenever available
• Capsules can be opened and taken immediately with food or water
• Tablets can be crushed and given immediately with water or little food
Drug Side effects
Abacavir (ABC) HA, GI upset and rash,lactic acidosis, hepatomegaly with
steatosis, potentially fatal hypersensitivity reaction
Didanosine (ddI) diarrhea, abdominal pain, N/V.
increased LFTs, lactic acidosis with hepatomegaly and
steatosis, peripheral neuropathy, hyperuricemia.
pancreatitis which is rare in children.
Lamivudine (3TC) Safest of all NRTI’s,HA, nausea, abdominal pain.
Stavudine (d4T) HA and GI intolerance,peripheral neuropathy, lipoatrophy.
lactic acidosis with severe hepatomegaly and steatosis.
Zidovudine (AZT neutropenia, anemia, granulocyptopenia, macrocytosis, and
or ZDV) HA,myositis, myopathy, mitochondrial disease.
Nevirapin (NVP) skin rash, HA, nausea, diarrhea. Steven Johnsons syndrome,
TEN, fatal hepatitis.
Efavirenze (EFV) skin rash, somnolence, insomnia, abnormal dreams,
confusion, hallucinations.increased LFTs,Teratogenicity
Lopinavir/ diarrhea, nausea, vomiting,, increase in blood lipids
ritonavir (kaletra) pancreatitis, diabetes,hepatic toxicity, fat redistribution.
Nelfinavir diarrhea, nausea, vomiting,asthenia, abdominal pain, rash,
lipodystrophy.
Single drug substitution for toxicity in children
First-line ARV drug Most frequent significant toxicity Suggested first-line
for the ARV drug* ARV drug substitution
ABC Hypersensitivity reaction AZT
AZT Severe anemia or neutropenia d4T or ABC
Lactic acidosis ABC
Severe gastrointestinal intolerance d4T or ABC
d4T Lactic acidosis ABC
Peripheral neuropathy
Pancreatitis AZT or ABC
Lipoatrophy/metabolic syndrome
EFV Persistent and severe central nervous system
toxicity NVP
Potential teratogenicity
NVP Acute symptomatic hepatitis EFV
Hypersensitivity reaction Triple NRTI (disadvantage,
Severe or life threatening rash (Stevens- may be less potent)
Johnson Syndrome) PI (disadvantage,
premature start of second-
line ARV drug)
 Drug combination that should not be used
d4T + AZT both drugs work through common metabolic pathways

d4T + ddI both drugs have overlapping toxicities

*TDF + ddI both drugs work through common metabolic pathways

*TDF + ABC both drugs select for the K65R mutation

* TDF is not used in pediatric age group because of bone demineralization

Treatment failure in children

• Should be defined after at least 6 months of ART

• The most common cause is poor adherence

• Where possible, viral load should be used to confirm suspected

clinical or immunological treatment failure

132
Issues to consider regarding treatment failure
• Check adherence-was it adequate
• Treatment failure defined based on growth failure-nutrition,
inter-current illness
• Developing TB while on 1st line regimen-what is the response
to anti-TB
• Exclude IRIS
• Do not measure CD4 during inter-current illness

133
Criteria to define treatment failure
Clinical definition of treatment failure

The detection of new or recurrent WHO clinical stage 3 or

4 events in a child on ART for 24 weeks and is adherent to
therapy

134
Immunological definition

• Developing or returning to the following thresholds after 24 weeks of

ART in an adherent child:
• <24 months- based on clinical criteria and /or virologic assessment with expert
opinion
• ≥2 years to <5 years of age CD4 count of <200 cells/mm3 or %CD4+ <10
• ≥5 years of age CD4 count of <100 cells/mm3

135
Virologic treatment failure in children
• A persistent viral load over 5,000 copies/ml in a child
adherent to ART regimen for more than 24 weeks.

136
Clinical and CD4 Definition of Treatment Failure in Children

Usually is considered after 6 months or more of ARV:

137
Immune Reconstitution Inflammatory Syndrome (IRIS)

• IRS/IRIS is characterized by a clinical deterioration after starting ART,

• is a result of the immune system interacting with latent infections.
• It is important to differentiate IRS from treatment failure
• management is very different.
• Unlike in treatment failure there will be an increament in the CD4 count
(%) and reduction in viral load.
• Treatment failure results in disease progression with development of
opportunistic infection or malignancy after drugs have been given sufficient
time to induce a protective degree of immune restoration (at least 24 weeks of
ARV therapy).
• There will be a decline in CD4 and an increament in viral load

138
Cont…
• IRIS usually occurs within the first several weeks after initiation of
HAART if there is a subclinical infection present at baseline.
• Several different pathogens can be reactivated causing IRS.
• In children the commonest is Mycobacterium tuberculosis, others are
Mycobacterium avium complex, Cryptococcus neoformans, Varicella
Zoster virus and Herpes Simplex virus.
• Management of IRS includes specific treatment for the infection and
symptomatic therapy.
• In severe cases glucocorticoids are helpful.

139
TB Treatment and HAART
• Growing evidence that better outcomes if a patient is treated with
HAART earlier in TB treatment
• weigh against risks (drug interactions, IRIS)
• Critically ill patient with severe immunosupression - Start anti TBc
and start ART after two weeks.
• If patient has advanced immunosupression and relatively well then
finish intensive phase and start ART during continuation phase.
• If patient is stable with moderate to advanced immunosupression
delay ART until he/she finishes anti TB and re-evaluate

140
Cont…
• Recommended ARV’s with anti Tb drugs:
• If ≥ 3 years and weight > 10kg:
• AZT + 3TC + EFV
• If <3 years or weight < 10kg:
• AZT + 3TC + ABC or
• AZT + 3TC + super-boosted PI (e.g. LPV/r+RTV)
• After TB treatment complete, change to the usual first line HAART

141
National Infant Feeding Recommendations in the Context
of Maternal HIV Infection
Ethiopia’s preferred infant feeding option for HIV-infected women:
• Exclusive breastfeeding for 1st 6 months
• Appropriate complementary foods should be introduced at 6
months with continued breastfeeding
• Breastfeeding should stop only when a nutritionally adequate diet
without breast milk can be provided (usually after 18 months)
• Infants determined to be HIV-infected should continue to
breastfeed according to recommendations for the general
population( until 2 years of age)

142
Risk factors for post-natal HIV transmission
• Mother with recently acquired infection
• Advanced HIV disease is in the mother
• High viral loads in blood or breast milk
• Low CD4 counts
• Longer exposure to breast milk
• Transmission of HIV can occur at any point during lactation
• Transmission rates increase with duration of breast-feeding
• Mixed feeding
• Maternal breast problems
• Mastitis
• Cracked nipples
• Conditions of baby’s mouth
143
How can postnatal transmission be decreased?
• Screen All mothers for HIV
• Treat All mothers
• Treat all pregnant and lactating HIV-infected women .
• Actively support exclusive breastfeeding for as long as possible until 6
months
• Avoid mixed feeding
• Avoid early weaning
• Avoid abrupt weaning
• Complementary feeding should be initiated after 6 months and
breastfeeding should continue until at least 18 months

144
National Recommendations
Alternative infant feeding option:
• For women who choose to use replacement feeding, every effort
should be made to ensure that it is done SAFELY

• Home-modified animal milk shall be used only as a temporary gap-

filling measure, for short duration, otherwise infant formula is
preferred for the 1st 6 months of life

145
Common Illnesses and opportunistic
infections in HIV-infected children

146
Common Infections
• Recurrent bacterial infections
• Account for about 20% of AIDS defining illnesses in infants and children
• Most are caused by encapsulated organisms such as S. pnuemoniae and
Salmonella, others are Staphylococcus, Enterococcus etc
• Most common serious infections are – pneumonia, bacteremia, sepsis and
meningitis (account for more than 50% of infections in HIV-infected children)
• Clinical features
• Similar as in HIV uninfected children, but may have protracted fulminant
course with rapid progression
• Management
• Same as in non HIV-infected children
• Occasionally may require longer duration of treatment 147
Pneumonia
• Major cause of morbidity and mortality in HIV-infected children and is
one of the most common reasons for hospitalization
• S. pneumoniae and H. influenzae type b, and S. aureus are the most
frequent pathogens
Clinical Manifestations:
• Same as in non HIV-infected children.
• However, recurrent episodes (2 or more episodes per year or more than 3
episodes in a life time) and bacteremia are more common.
• Severe recurrent bacterial pneumonia suggests moderate to severe
immune suppression (WHO Stage3).
148
• Diagnosis:
• Clinical
• CXR is indicated specially if recurrent and/or severe or does not
respond to standard treatment management
• Treatment:
• Same as in non HIV-infected children
• Children who do not respond to standard therapy should be
investigated for Tuberculosis.

149
Opportunistic Infections (OI)

Definition :-
• OIs are infections that develop as a result of damage to the
immune system
• OIs take advantage of the opportunity provided by a
weakened immune system
• Infections tend to appear at predictable stages of immune
deterioration
Natural History of HIV Infection
500 vaginal candidiasis
skin disease
fatigue
bacterial pneumonia
CD4 Count

herpes zoster
oral hairy leukoplakia, thrush,
fever, diarrhea, weight loss
200 Kaposi’s sarcoma, non-Hodgkin’s lymphoma
Pneumocystis carinii pneumonia
100 Toxoplasmosis, esophageal candidiasis,
cryptococcosis
50
CMV, MAC, CNS lymphoma

Time
Cont…
• 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
• In children with severe immunodeficiency clinical manifestations may
vary

152
Pneumocystis Pneumonia (PCP)

Epidemiology
• Caused by Pneumocystis jiroveci- fungus
• In HIV-infected children, highest incidence during the first year of life
and usually peaks at 3-6 months of age
• High morbidity and mortality rate - major cause of severe pneumonia
(15-30%) and death (30-50%) in HIV-infected infants
• AIDS defining condition – WHO Stage 4
Pneumocystis Pneumonia (PCP)
• Accounts for 57% AIDS-defining cases among infants < 1 year
• Acquired in childhood – 80% are serology positive by 2-4 years
• CD4 count is not a good indicator of risk in infants. Count drops
rapidly before PCP develops
Clinical Manifestations

• Onset can be abrupt or insidious

• Low grade fever or afebrile
• Marked respiratory distress (chest in-drawing, cyanosis, inability to
drink, marked tachypnea)
• Ausculatation: clear chest or diffuse fine crepitations
• Poor response to standard antibiotic treatment
• Pulse oximetry: severe persistent hypoxia (paO2 < 90%)
• Occasionally, associated with other HIV symptoms including oral
thrush, lymphadenopathy, and/or weight loss
Diagnosis
• PCP is a clinical diagnosis
• CXR:
• may be normal
• bilateral diffuse parenychmal infiltrates with “ground glass” or
reticulogranualr appearance
• Isolation of organism in:
• Induced sputum
• Broncho-alveolar lavage
• Tissue biopsy
• Tests not routinely done
PCP Chest X-Ray
Management

• Initiate therapy promptly on clinical suspicion, along with treatment

for bacterial pneumonia
• Treatment
• Give high dose cotrimoxazole 20 mg/kg of trimethoprim per day
intravenously OR orally given in 3-4 divided doses for 21 days
• Add prednisone at 2 mg/kg/day for 7-14 days if child is in severe respiratory
distress (taper if treatment > 7 days)
Cont…

• Supportive
• Provide oxygen therapy
• Maintain and monitor hydration
• Provide paracetamol for pain (caution in babies less than 3 months)
• Continue therapy for bacterial pneumonia
• Follow-up
• After an acute episode provide PCP prophylaxis for life
• Counseling and testing must be provided for family and the appropriate referrals for services
be made
• Management alternatives
• Clindamycin and primaquin
• Dapsone
Pneumocystis Pneumonia:
Prevention - Cotrimoxazole Prophylaxis
• Highly effective in preventing PCP but also effective in preventing
other infections:
• Pneumococcus
• Non-typhoidal salmonella
• Toxoplasmosis
• Isospora belli
• Other bacterial infections
• Malaria (plasmodium falciparum)
• Reduces morbidity, mortality and hospitalization in HIV- infected
children
Guidelines for Cotrimoxazole (CTX) Prophylaxis

• All HIV-exposed infants beginning at 4-6 weeks of age until breastfeeding

cessation and exclusion of HIV infection
• All HIV infected children < 12 months
• regardless of CD4 or clinical status
• HIV-infected children aged between 1-4 years
• WHO Stages 2, 3 or 4 regardless of CD4
• WHO Stage 1 if CD4 cell count is < 25%
• HIV-infected children >5 years, as recommended for adults
• CD4 < 350 irrespective of clinical stage
• Where CD4 is not available, WHO Stage 3, 4
• All children with prior PCP pneumonia
• Children < 18 mo with presumptive severe HIV disease
When to stop CPT
A. Secondary prophylaxis
 Life-long
B. Primary prophylaxis
 In general, continued prophylaxis is recommended in resource limited
settings, irrespective of immune response to ART

162
Candida: Epidemiology
• Most common fungal infections in HIV-infected children caused by
candida species
• Oral thrush and nappy dermatitis occur among 50-85% of HIV-
infected children
• Candida albicans most common cause of mucosal and esophageal
candidiasis
• Esophageal candidasis is WHO Stage 4 condition – associated with
low CD4 and high viral load
• Disseminated infection infrequent, but more likely with co-infection
with HSV or CMV
 Common Oral Manifestations
• Oral candidiasis is the most common
oral condition in HIV infected
children

• Three forms
• Atrophic (erythematous) • Management
candidiasis • Oropharyngeal:
• Pseudomembraneous • Nystatin 100,units/ml;1-2ml
four times a day
• Angular Cheilitis • Oral miconazole gel 2.5 ml twice
aday.
• Fluconazole 3-6mg/kg daily for
7-14 days
• Dysphagia and poor oral intake, • Esophageal disease: Fluconazole
irritability indicates involvement of 6mg/kg on day one then 3-6mg/kg
daily for minimum of 14-21 days
the esophagus 164
Oral ulcerations
• Ulcers on gums, hard palate and edges of the lips, but any mucosal
surface may be involved

• Presents as vesicles which rupture to become painful, irregular ulcers

• Recurrent forms are more severe, extensive and persistent in HIV

patients.

165
Herpetic ulceration

166
Common Skin Manifestations: Bacterial skin
infections
• Folliculitis, cellulitis, skin
abscesses impetigo, furunculosis
and paronychia may occur with
increasing frequency
• Staphylococcus aureus is the
cause in most bacterial skin
infections
• Good hand washing is needed to
prevent spread of lesion
• Treatment: Erythormycin or
cloxacillin
167
Impetigo
Common Skin Manifestations: Molluscum
contagiosum
Common childhood viral
infection characterized by:
discrete, dome shaped, pearly
white papules with central
umblication
Transmitted by skin to skin
contact, self limited in most cases
Extensive Molluscum
In HIV-infected children
Treatment
M.congtagiosum tends to be
extensive- covering > 5% of the  ART
body surface area  Treatment: liquid nitrogen,
curettage
168
A child with molluscum before and after ART

169
Common Skin Manifestations: Scabies
• Pruritic papular eruptions
• In infants and children tend to
involve the sole and the palms
• Diagnosis is made clinically
• Norwegian Scabies: generalized
scaling and enlarged crusted Scabies lesions on mother and infant
plaques
• Treatment:
• 5% permethrin
• Benzylbenzoate lotion 25%
• 10% sulfur ointment
Norwegian scabies
Source: Common Skin Diseases In Africa, Colette van Hees & Ben Haafs 170
Common Skin Manifestations: Seborrheic
Dermatitis/eczema
• Extensive and an early non specific sign Seborrheic dermatitis of the axilla
of HIV infection in infants
• Thick yellow scales on the scalp but thin
scales over the rest of the body
• High recurrence
• Treatment
• Topical steroids

Source: Common Skin Diseases In

Africa, Colette van Hees & Ben Haafs 171
Common Skin Manifestations: Pruritic Papular
Eruptions (PPE)
• Chronic papular lesion
• Etiology unknown
• Evenly distributed over the trunk and
extremities
• A marker of worsening
immunosuppression and may be
stigmatizing
• Risk of secondary bacterial infection
• Treatment:
• Antihistamines and steroids

Papular Pruritic Eruptions

Source: Common Skin Diseases In Africa, Colette van Hees & Ben Haafs

172
Common Skin Manifestations: Viral
Infections

• Herpes Zoster
• Recurrent, atypical and • Chickenpox
• May be prolonged and complicated by
chronic, multidermatomal bacterial infection or visceral
and may need use of dissemination or pneumonitis
acyclovir
Source: Common Skin Diseases In Africa, Colette van Hees & Ben Haafs
173
Common CNS Manifestations
• Occurs in 50 – 90% of perinatally infected children in developing
countries, with a median onset at 19 mo
• Manifestations may range from subtle developmental delay to
progressive encephalopathy
• Encephalopathy may be :
• The initial manifestation of the disease or may
• Present much later when severe immune suppression occurs

174
Cont…
• Most common form is progressive encephalopathy
• Loss or plateau of developmental milestones
• Cognitive deterioration
• Impaired brain growth resulting in acquired microcephaly
• With progression, marked apathy, spasticity, hyperreflexia and gait
disturbances and loss of language and other motor skills
• CT shows cerebral atrophy in 85% of children
• The encephalopathy may progress intermittently, with periods of
deterioration followed by transiently stable plateaus
• Older children may exhibit behavioral problems and learning disabilities

175
• Focal neurologic signs and seizures are unusual and may imply a co-
morbid pathologic process
• CNS lymphoma
• Toxoplasmosis
• Tuberculoma
• Stroke

176
Common Cardiovascular Manifestations
• Dilated cardiomyopathy, persistent tachycardia and left ventricular
hypertrophy are common
• With advanced disease high frequency of autonomic instability leads
to rhythm abnormality
• Gallop rhythm, tachypnea, hepatosplenomegaly indicates CHF
• Anticongestive therapy is effective
• Cardiac complications are associated with poor prognosis

177
Common GI Manifestations
• Most frequent GI symptoms: persistent or recurrent diarrhea with
malabsorption, abdominal pain, dysphagia and failure to thrive
• A variety of pathogens cause GI symptoms:
• Bacteria (salmonella, campylobacter, MAC)
• Protozoa (Giardia, cryptosporidium, Isosporia, microsporida)
• Viruses (CMV, HSV, Rotavirus)
• Fungi (Candida)
• MAC and protozoal infections are severe and protracted
• Other GI manifestations are
• Chronic liver inflammation with or without jaundice
• Pancreatitis with or without abdominal pain
• Chronic cholecystitis
• Management depends on underlying pathology
• Diarrheal illnesses are managed as per the IMCI guideline
178
 Common Hematologic Manifestations
• Unexplained Anemia: • Leukopenia:
• Up to 1/3 (30%) of infected
• 20– 70% of HIV-infected children
children • ANC < 1000/mm3
• Hb < 8g/dL • Other causes: drugs, OI like CMV,
• Causes: chronic infection, MAC
poor nutrition, autoimmune
factors, virus associated
conditions (hemophagocytic • Thrombocytopenia:
syndrome, parvovirus B19 red • 10– 20% of infected children
cell aplasia), or the adverse • Platelet count < 50,00/mm 3

effect of drugs (zidovudine). • Causes: drugs, autoimmune, OIs,

ARV drugs 179
Common Malignant Diseases
Generally less frequent compared to adults and
represent less than 2% of AIDS defining illnesses in
children
Most frequent:
Non Hodgkins lymphoma
Primary CNS lymphoma
Leiomyosarcoma
Acute lymphoblastic leukemia
Epstein-Barr virus is associated with most cases of
lymphomas and all cases of leiomyosarcoma
180
Common Malignant Diseases- KS
• Kaposi sarcoma due to human
herpes virus 8 occurs less
frequently than in the adults
• Vascular tumor that presents on
the skin and internal organs
• Treatment
• Optimize ART
• Chemotherapy

Source: Common Skin Diseases In Africa, Colette van Hees & Ben Haafs

181