HIV infection in children is a major public health problem, especially in Sub-Saharan Africa. Over 2.5 million children are living with HIV globally, with over 95% of pediatric infections resulting from mother-to-child transmission. Factors like high HIV prevalence in women of childbearing age and subtype C's increased virulence have led to high rates of pediatric infection in Tanzania and SSA. HIV depletes CD4+ T cells, impairing immune function and leaving children susceptible to opportunistic infections. Disease progression varies but can be rapid, with mortality high in infants under 2 years old due to inability to control high viral loads.

1. HIV infection in children
Paediatrics

2. Paediatric HIV Infection:
Epidemiology, biology, and
pathophysiology
Adapted from the National AIDS Control Program Curriculum
THE UNITED REPUBLIC OF TANZANIA
MINISTRY OF HEALTH & SOCIAL WELFARE

3. 2.5 million children, 90% in SSA
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4. • 1.3 million people (5.7%)
• 10% < age 15
• 12000 infant infections annually
Tanzania
• Prevalence 1.9%
Kilimanjaro region
Introduction: HIV epidemiology
UNGASS/TACAIDS (2010).

5. Modes of HIV Transmission to Children
• MTCT – responsible for 95% of infected infants
• Sexual transmission (adolescents/abuse)
• Transfusion of infected blood
• Unsterile injection procedures (2.5% in both adult
and paediatric population)
• Scarification

6. Factors Contributing To High HIV Prevalence In
Children In Sub-saharan Africa
• High prevalence of infection in women of
childbearing age
• Efficiency of MTCT where infection rates
among women (15-49 yrs) in Tanzania range
from 2% (Manyara) to 15.2% (Mbeya)

7. Consequences of the HIV Epidemic on Children
AIDS impacts children in many ways
• Increased infant and childhood morbidity
• Increased infant and childhood mortality
• Increase in number of orphaned children
• Increased deprivations in various forms;
– Mental
– Psychological
– School dropouts
• Abuse : Physical, Sexual

8. HIV epidemiology - summary
• Over the past 2 decades HIV has spread worldwide with devastating
epidemiological consequences particularly in Sub Saharan Africa
• MTCT is the greatest mode of transmission of HIV infection in
children.
• The burden of HIV/AIDS among Tanzanian children is high: 72,000
new infections each year, 140,000 total infections, and a high
proportion of orphaned children (11% of children under 18)

9. HIV biology

10. 4/23/2015
The Biology of the Human Immunodeficiency Virus
HIV – 1
• Is found worldwide
• Is the main cause of
the worldwide
pandemic
NB: Unless otherwise
specified, ‘HIV’ in this
training refers to HIV-1
HIV – 2
• Mainly found in West Africa,
Mozambique and Angola.
• Causes a similar illness to
HIV – 1
• Less efficiently
transmissible, rarely causing
vertical transmission
• Less aggressive, slower
disease progression
There are two types of HIV:

11. 4/23/2015
HIV-1 SUBTYPES
• HIV-1 has many subtypes: A-K
• A-E are the predominant subtypes
– A: W. Africa, E. Africa, Central Africa East Europe &
Middle East
– B: N. America, Europe, Middle East, E. Asia, Latin
America
– C: S. Africa, S. Asia, Ethiopia
– D: E. Africa
– E: S. E. Asia

12. 4/23/2015
HIV-1 Subtype Distribution in Africa
• East and Central Africa
has mainly subtype A
and D.
• Southern Africa mainly
subtype C.
• West Africa mainly A
• Different subtypes can
combine to form
diverse recombinants.

13. 4/23/2015
HIV SUBTYPE C
• This is the most virulent subtype.
• It has higher transcription rates.
• In Tanzania is associated with higher MTCT
rates than subtype A.
• Is associated with faster disease progression in
adults.

14. 4/23/2015
Viral Enzymes
• The most important are Reverse Transcriptase (RT), Protease and Integrase.
• RT converts viral single-stranded RNA into a single strand deoxyribonucleic
acid (DNA).
– DNA polymerizes to form a double stranded DNA (dsDNA)
– DNA is incorporated into host nucleus as the proviral DNA.
• Integrase facilitates integration of the dsDNA into the host’s chromosomal
DNA.
• Protease enzyme splits generated macro-proteins into smaller viral proteins
(core, envelope & regulatory proteins and enzymes) which are then
incorporated into the new viral particles.

15. 4/23/2015
HIV - Replication
Fusion & viral entry
Reverse
transcription
Integration
Transcription -
Translation
Protease
activity
Assembly
& budding
HIV Life Cycle

16. 4/23/2015
HIV biology - summary
• Rapid replication of HIV causes genetic diversity
of the virus
• Knowledge of HIV structure is important in
understanding the mechanism of ARV drugs
• Current ARV drugs act mainly by antagonizing
various HIV enzymes necessary for viral
replication

17. HIV pathophysiology

18. Cells Of The Immune System
• Found in blood and tissues
• In blood mostly are white blood cells (WBC)
– Macrophages act as clearing cells
– Neutrophils attack bacteria
– Eosinophils attack helminths (and mediate
allergies)
– B-lymphocytes make antibodies

19. Cells of the Immune System
– T-lymphocytes
• Responsible for attacking viruses, fungi and
some bacteria
• T helper cells central in orchestrating
function of other immune cells
– T killer cells are able to destroy infected cells

20. How HIV Affects the Immune System
• HIV attaches to cells of the immune system with
special surface markers called CD4 receptors
• The following immune cells have CD4 receptors
• T-Lymphocytes – CD4 Cells
• Macrophages
• Monocytes
• Dendritic cells

21. HIV Effect on Immune System
• The hallmark of HIV/AIDS is profound
immunodeficiency as a result depletion of
CD4+ T lymphocytes.
• The CD4+ T cell dysfunction is two fold:
– Reduction in numbers
– Impairment in function

22. HIV Effect On Immune System
• Reduction in the CD4 cell number and the
effects on their function reduces the capacity
of the body to fight infectious diseases
• Individuals with HIV infection are therefore
increasingly susceptible to many infections
especially at later stages of HIV infection

24. HIV Effect On Other Parts Of Immune System
• Lymphoid tissue destruction
• CD8+ cell dysfunction
• B cell abnormalities
• Thymic dysfunction
• Autoimmune abnormalities

25. Immunological Parameters in Children:
Background
Immunological Parameters
• Absolute CD4 count higher in healthy children than in
adults.
• Absolute CD4 count varies with age
• Normal absolute CD4 counts slowly decline to adult levels
• CD4 percentage does not change with age.
• In children < 5 yr CD4 percentage is the preferred
immunological parameter for monitoring disease
progression.

26. Immunological Parameters in
Children: Background
Age-related Decrease in CD4+ Number
0
2000
4000
6000
Age in Months
CD+Number/mm3
5th percentile
95th percentile
4 12 24 6090

27. Immunological Parameters in
Children: Background
Age-related Decrease in CD4+
Percentage
0
20
40
60
80
Age in Months
CD4+%
5th percentile
95th percentile
4 12 24 6090

28. Natural History: Immunologic
Parameters
• CD4 count/percentage declines with disease
progression
• Rapid decline results in risk of developing AIDS or
death as CD4+ cell percentage decreases below
15–20%.
– Prognosis poorer in infants <12 months than in older
children

29. Natural History: Immunologic
Parameters
• CD4+ T cell count and CD4% are useful when caring for HIV-infected
infants and children
• The CD4+ T cell count or percentage value is used in conjunction with
clinical indicators to guide antiretroviral treatment decisions
– CD4+ T cell values can be associated with considerable intra-patient
variation.
– Transient decreases may be associated with intercurrent illnesses &
vaccinations
– CD4+ T cell values are best measured when patients are clinically
stable.

30. HIV RNA in Children
The HIV RNA pattern in perinatally infected infants
differs from infected adults (90% pediatric HIV is perinatally-
acquired)
In Infants:
• RNA levels are low at birth.
• Increase to high levels > 100,000-millions of copies/ml by 2 months
of age.
• Remain high throughout the first year of life.
• Decline slowly over the next few years to “set point”.

31. VL VL
Adults Infants
“Set point”
3 months 1 yr
HIV RNA Response in Infants Compared to
Adults
•The mortality in young children under 2 years is very high
•Infants have much higher viral loads than adults

32. HIV RNA In Children
• This pattern is due to inability of the
infant’s immature immune system to
contain viral replication.
• There is also a greater number of HIV
susceptible cells.
• High RNA levels and low CD4 counts (<15%)
are independently predictive of increased
risk of progression to AIDS and death.

33. HIV RNA in Children
• Children > 12 months with HIV RNA >100,000 copies/ml are at
higher risk for disease progression and death
• Prognostic value of RNA in infants < 12 months old is less than
in older children
– CD4 percentage therefore is a better prognostic indicator of risk of
disease progression and death in infants < 12 months

34. HIV Disease Progression In Children In Africa
Category 1 (25 – 30%):
Rapid disease progression; infants die within 1 year. Disease
acquired in utero or perinatally.
Category 2 (50 – 60%):
Children who develop symptoms early in life.
Deteriorate and die by 3 to 5 years.
Category 3 (5 – 25%):
Long-term survivors who live beyond 8 years of age.

35. Progression
Early Severe Form Characterized by
• Low birth weight
• Developmental delay
• Persistent oral candidiasis
• Recurrent/persistent diarrhoea
• Recurrent bacterial/fungal infections
• Severe encephalopathy before 18 months
• High viral load at birth
• Rapidly decreasing CD4 counts

36. Progression
Slow Progression
• Opportunistic Infections after 2 - 10 years
• No encephalopathy, growth stunting common
• Lymphoid interstitial pneumonitis (LIP), parotitis
• Recurrent bacterial and fungal infections
• Skin problems
• AIDS related cancers
• Low viral loads at birth, stable CD4 counts for 2 - 10 years then
slow decline

37. Natural History of HIV
Factors that related to disease progression are:
• The child’s immature immune system
• Size of infecting viral dose
• Maternal disease status
• Infant peak viremia
• Infant CD4+ cell counts