HIV infection in children
Paediatrics
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
2.5 million children, 90% in SSA
3LPM
8.7% of pregnant
12000 New HIV infections yearly in
• 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).
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
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)
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
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)
HIV biology
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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:
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
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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.
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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.
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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.
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HIV - ReplicationFusion & viral entry
Reversetranscription
Integration
Transcription -Translation
Protease activity
Assembly& budding
HIV Life Cycle
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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
HIV pathophysiology
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
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
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
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
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
HIV Effect On Other Parts Of Immune System
• Lymphoid tissue destruction
• CD8+ cell dysfunction
• B cell abnormalities
• Thymic dysfunction
• Autoimmune abnormalities
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.
Immunological Parameters in Children: Background
Age-related Decrease in CD4+ Number
0
2000
4000
6000
Age in Months
CD
+ N
um
ber/m
m3
5th percentile
95th percentile
4 12 24 6090
Immunological Parameters in Children: Background
Age-related Decrease in CD4+
Percentage
0
20
40
60
80
Age in Months
CD
4+
% 5th percentile
95th percentile
4 12 24 6090
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
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.
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”.
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
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.
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
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.
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
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
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