Download Natural course of HIV Infection in children

Natural History
of HIV Infection in Children
HAIVN
Harvard Medical School AIDS
Initiative in Vietnam
1
Learning Objectives
By the end of this session, participants
should be able to:
 Describe the characteristic, structure of
HIV
 Describe the and transmission route of
HIV
 Describe the HIV life cycle
 Explain HIV pathogenesis
 Describe the natural history of HIV
disease progression in children
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Basic Concepts
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HIV Virology



HIV: Human Immunodeficiency Virus
HIV is an RNA virus
HIV is a “retrovirus”:
• replication occurs from RNA to DNA
using the enzyme “reverse transcriptase”
• the DNA created is then integrated into
the host cell genome (T lymphocyte)
• further HIV virus is then produced using
this DNA complex
• Two types: HIV1 and HIV2
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HIV Virion
p24
HIV virion taken with
electronic microscope
Source of pictures: wikipedia
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CD4 Cell – Definition

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CD4 cell is one type of T-Lymphocyte
HIV binds with receptors on the CD4
cell to enter and infect the cell
After infection, the number of CD4
cells gradually declines over time
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CD4 Count - Definition


The CD4 cell count is the number of
CD4 cells in a cubic millimeter of
blood
The CD4 cell count indicates extent
of HIV-induced immune damage
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Viral Load – Definition



The viral load is the amount of HIV in
the blood
The level of HIV in the blood
indicates the magnitude of HIV
replication and rate of destruction of
CD4 cells
The viral load test measures the
amount of HIV RNA in the plasma
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How is HIV Transmitted?

Blood/Parentally
• IV drug use
• Occupational exposure (needle sticks)

Unprotected sexual contact with
infected partner/s
• Heterosexual or homosexual

Perinatally (mother to child)
• During pregnancy and labor
• Through breastfeeding
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Transmission Activity
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Estimated HIV Risk for a Single
Exposure to HIV Source
Blood Transfusion
Mother to child
25-35%
IDU needle sharing
0.67%
Occupational needle stick
Receptive anal sex
Receptive vaginal sex
Insertive anal sex
90%
0.3%
0.5%
0.1%
0.065%
Insertive vaginal sex
0.05%
Receptive oral sex
0.01%
Insertive oral sex
(CDC, MMWR, 2005)
0.005%
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What Characterizes HIV
Transmission?

HIV is spread only
through exposure
to certain bodily
fluids:
•
•
•
•
Blood
Semen
Vaginal secretions
Breast milk

In order for HIV to
be spread, infected
fluids need to be
exposed to:
• a mucous
membrane (vagina,
eye, mouth)
• broken skin
• blood (needle stick,
infusion)
HIV is difficult to transmit even through risky
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behaviors
How is HIV not Spread?
HIV is NOT transmitted through casual
contact such as:
•
•
•
•
•
•
Hugging or kissing
Coughing or sneezing
Sharing utensils, cups or bowls
Sharing toilets
Swimming pools
Insect bites
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How Does HIV Infect
the Human Cell?
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5
1
6
HIV
RNA
2
Reverse transcriptase
3
4
7
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HIV Pathogenesis
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What Happens after HIV Virus
Enters the Bloodstream?

Virus:
• enters dendritic cells and macrophage and
• is carried to regional lymph nodes, and:


infects CD4 cells
produces virions, which in turn infect other CD4
cells
• also goes into other body compartments
Virus causes deaths of massive number
of memory CD4 cells (impairing ability
to fight infections later on)
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Pathogenesis of HIV-infection:
Compartments
Dendritic cells, macrophage
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Pathogenesis of HIV-infection (1)

Rapid HIV virus production results in:
• depletion of CD4 lymphocytes and
• a weakened immune system

HIV may also lay dormant in the host
cell after integration into host DNA
(the reservoir)
• These viruses are not affected by ARVs
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Pathogenesis of HIV-infection (2)
Two main types of injury caused by HIV
Direct injury
• encephalopathy
• peripheral
neuropathy
• cardiomyopathy
• nephropathy
Indirect injury
• Immuno-suppression:
• opportunistic infections
• malignancies
• Immuno-dysregulation:
• Autoimmune: thyroid
dysfunction, psoriasis
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Natural History
of HIV Infection in Children
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Natural History
Untreated HIV infection
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Bimodal Progression of AIDS and
Deaths in HIV-infected Children
AIDS
Deaths
1 year
5 year
Deaths
10 - 35%
40 – 50%
AIDS
25 – 30%
40 – 43%
Immune suppression
10 -20%
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>50%
Patterns of HIV Disease
Progression in Children (1)
Rapid
progressors
• 10-25% of infants develop
profound immunosuppression and
AIDS usually within the first 2
years of life
Slow
progressors
• About 75% children have a slower
progression to AIDS with a mean
time of 5-6 years
Long-term
nonprogressors
• Some children remain asymptomatic
for a long time without ART
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Patterns of HIV Disease
Progression in Children (2)

Long-term non-progressors:
• Prevalence: about 2%, similar to adults
• Definition:

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Age ≥10
Never have CDC category B/C disease
(=WHO stage 3/4)
CD4 > 25%
Never been on ARV except AZT
Source: Warszawski et al. Clinical Infectious Diseases 2007; 45:785–94
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What are Risk Factors for
Disease Progression in Children?


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In utero or perinatal transmission
High viral load and advanced disease
in mother
Stage III/IV conditions, esp.
encephalopathy
Low CD4 cells/percentage
High plasma viral load
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Risk Factors for
Disease Progression in Children

NOTE: Normal CD4 or low VL does
not have predictive value in young
children < 2, i.e. those with normal
CD4 or low VL can still develop
severe disease and die.
This is the basis for treating
all HIV-infected children under 2 y.o
regardless of clinical and immunological stage
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Common OIs/Conditions in
Vietnamese Children
 Infants may be symptomatic in the 1st year,
after that, the majority of them tend to be:
• asymptomatic or
• only with mild symptoms
 Below is the list of common OIs/conditions:
• Respiratory infections,
including PCP
• Tuberculosis
• Oral candidiasis
• Diarrhea
•
•
•
•
•
PPE/dermatitis
Herpes varicella zoster
Otitis media
Hepatosplenomegaly
Failure to thrive
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Plasma Viremia in
Vertically HIV-infected Infants
Copies/ml
Viremia is extremely high
in the first 6 months,
then gradually declines
Viral load
Time
6 months
Viral Load
(Copies/
ml
Birth – 6
≥106
months
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105 -105.5
months
5 years
≤ 105
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CD4 Percentage/Count:
Which to Use?
Age
Parameter
to use
CD4
percentage
< 5 y.o
(%) is
preferred
Comment
 the absolute CD4 count is
generally not used due to:
• high inter-measurement
variability and
• age-related decline
 CD4% is more constant
 the CD4 count pattern is
similar to that of adults in
≥ 5 y.o CD4 count
this age group
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Role of CD4 Percentage/Count

CD4 is extremely useful for:
•
•
•
•
when to start prophylactic medications
when to start ARV treatment
monitoring response to treatment
predicting risk for OI’s
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Natural History of
HIV infection treated with ART
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HIV infection treated with ART

Combination ART is associated with
improvement in:
• virologic,
• immunologic, and
• clinical health for HIV-infected adults
and children
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Declines in mortality rates in HIV infected children
during the HAART era
7.2
Between 1994 and 2000, the
mortality rate decreased 7.2 to 0.8
deaths per 100 person-years;
mortality rate was inversely
associated with HAART treatment
0.8
Brady MT, Oleske JM, Williams PL, et al. Declines in mortality rates and changes in causes of death in HIV-1infected children during the HAART era. J Acquir Immune Defic Syndr 2010; 53:86.
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Effectiveness of pediatric antiretroviral therapy in
resource-limited settings
70 % of children attained virologic suppression
increase of 13.7 percent in CD4 percentage
Ciaranello AL, Chang Y, Margulis AV, et al. Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a
systematic review and meta-analysis. Clin Infect Dis 2009; 49:1915.
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Key Points

After infecting CD4 cells, HIV multiplies
rapidly, resulting in:
• depletion of CD4 lymphocytes
• weakened immune system

3 patterns of HIV disease progression in
children are :
• Rapid progressors
• Slow progressors
• Long-term non-progressors

In infants infected perinatally, viremia is
extremely high in the first 6 months, then
gradually declines
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Key Points

CD4 count is the best way to:
• Determine degree of immune suppression
• Make treatment decisions
• Monitor for treatment response

Combination ART is associated with
improvement in:
• Virologic
• Immunologic
• Clinical health for HIV-infected children.
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Thank you!
Questions?
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