Download Clinical Course of HIV Infection

Natural Course of HIV
Infection
HAIVN
Harvard Medical School AIDS
Initiative in Vietnam
1
Learning Objectives
By the end of this session, participants
should be able to:
 Describe the natural progression of
HIV infection
 Explain the factors that influence the
progression of HIV infection
2
Basic Concepts of HIV
Virology
3
Overview of Virology

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Viruses are classified as either DNA or
RNA viruses
The building blocks of viral genes are
nucleotides
RNA and DNA are made of nucleotides,
which code for the production of
proteins
These proteins are the components of
the virus (envelope, antigens, enzymes
etc)
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Overview of HIV Virology


HIV is an RNA virus consisting of
9200 nucleotides
HIV is a “retrovirus”, meaning:
• replication occurs from RNA to DNA
using the enzyme Reverse Transcriptase
• DNA created is then integrated into the
host cell genome (T lymphocyte)
• further HIV virus (RNA and proteins) are
then produced using this DNA complex
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HIV Structure
6
Definitions (1): CD4 Cell
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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
The number of CD4 cells in the body,
or the CD4 cell count, indicates
extent of HIV-induced immune
damage
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Definitions (2): Viral Load
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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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Definitions (3): HIV Testing
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HIV antibody test identifies
antibodies to the HIV virus in the
blood
It takes 1-3 months following HIV
infection for the antibodies to be
detected on a standard HIV antibody
test
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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
11
Natural Progression of HIV
Disease
1000
CD4+ cell Count
900
Asymptomatic
Relative level of
Plasma HIV-RNA
800
700
600
500
CD4+ T cells
TB
Acute HIV
infection
syndrome
HZV
400
300
OHL
200
PPE
100
0
OC
PCP
TB
CMV, MAC
0 1 2 3 4 5
Months
1
2
3
4
5
6
Years After HIV Infection
7
8
9
10
11
12
Variable Progression of HIV
infection
Long term non-progression
CD4
500
Typical Progression
OI
200
OI
Rapid progression
Death
5yrs
10yrs
Death
15yrs
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Natural Progression of HIV
Infection
HIV progresses through various stages
which include:
Primary HIV Infection
2. Latent Period
3. Symptomatic HIV Infection
4. AIDS (advanced HIV Infection)
1.
14
Primary HIV Infection (1)
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Occurs 2-4 weeks after acquiring HIV
infection
Symptoms last 1-2 weeks and most
commonly include:
•
•
•
•
•
Fever
Myalgia/arthralgia
Pharyngitis
Adenopathy
Rash
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Primary HIV Infection (2)
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Seroconversion usually occurs within
4 –12 weeks, so HIV antibody tests
are usually NEGATIVE in this period
If primary HIV infection is suspected
and HIV test is negative, repeat test
after 1 and 3 months
HIV Viral Load testing can diagnose
acute HIV infection
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Primary HIV Infection (3)

A generalized rash is a common
finding:
• 5-10 mm macular or papular
erythematous lesions
• appears 48-72 hours after fever starts
• lasts for 5 – 8 days
• most often involves the face and trunk
• typically not pruritic
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Rash Associated with Primary HIV
Infection (1)
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Rash Associated with Primary HIV
Infection (2)
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Primary HIV Infection: Treatment
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Treatment is supportive
• Treat fever with paracetamol
• Treat pain with NSAIDS or opiates
• Maintain adequate hydration

Counsel patient on preventing
transmission to others
• Viral load at this stage is very high
ARV medications are not indicated for acute HIV
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infection
Latent Period
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Also known as asymptomatic HIV
disease
Characterized by gradual decline in
CD4 count
Patients may be healthy for 5-10
years before symptoms develop
• Symptoms can develop when CD4 <
500 cells/mm3
• OIs develop when CD4 < 200 cells/mm3
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Symptomatic HIV Infection
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Generally occurs when CD4 < 500
Conditions that may be seen when CD4
count is 200 – 500 include:
•
•
•
•
•
•
•
•
Generalized lymphadenopathy
Fatigue
Prolonged fevers or diarrhea for > 1 month
Oral or vaginal candidiasis
Bacterial pneumonia
Pulmonary tuberculosis
Herpes zoster (Zona)
Malignancy (Cervical cancer, lymphoma)
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Manifestations of HIV Infection Vary
Greatly
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Some patients with
CD4 > 200 can be
ill with many
symptoms
Some patients with
low CD4 < 100 can
feel healthy with
no symptoms at all

All patients have
decreased immune
function and are at
risk for OIs when:
• WHO Clinical Stage
3 or 4,
• CD4 < 200
• TLC < 1200
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AIDS (Advanced HIV Infection)
Final stage in the natural progression of HIV Infection
Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.
Criteria for Diagnosis
Advanced
HIV
Infection
Any condition under clinical stage 3 or 4
(presumptive or definitive diagnosis)
and/or
CD4 cell count < 350 cells/mm3
AIDS
Any condition under clinical stage 4
(presumptive or definitive diagnosis)
or
CD4 cell count < 200 cells/mm3
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What Factors Affect the Rate of
Disease Progression?

Speeds disease
progression:
• Age
• Symptoms during
primary HIV
• Nutritional status
• Opportunistic
infections (eg: TB)
• High viral load
• Intravenous drug
use?

Slows disease
progression:
• OI Prophylaxis with
cotrimoxazole
• Antiretroviral
Therapy
25
Laboratory Testing in HIV Patients
Two common tests used to evaluate
and follow HIV patients are:
• CD4 cell count
• Total Lymphocyte Count (TLC)
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CD4 Count (1)
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Normal CD4 count in adults is 5001500
In children < 5 years old, CD4 count
is higher and more variable
• Therefore, % CD4 cells is used to follow
HIV disease in children
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CD4 Count (2)
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Best test to measure effect of HIV on
immune system
Correlates with risk for developing OIs
and risk of death
Can be used to make treatment
decisions, e.g.:
• When to start prophylactic medications or
ARV treatment
• Which OIs are most likely when patient has
acute symptoms
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Total Lymphocyte Count (TLC)
(1)

If CD4 testing is not available, TLC and
WHO Clinical Staging can be used to:
• Estimate level of immunosuppression
• Decide when to treat with prophylactic
medications and ARV
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TLC < 1200 indicates CD4 may be low
Patients considered immune
suppressed, need cotrimoxazole
prophylaxis when WHO stage 2, 3 or 4
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Total Lymphocyte Count (TLC)
(2)
The Total Lymphocyte Count is easy to
calculate from the results of a CBC:
TLC = WBC x % Lymphocytes
Example: Hb 12.0
Hct 38%
WBC 4,800
Plt 165,000
65% Neutro
25% Lympho
9% Mono
1% Eos
What is the TLC?
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Key Points
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On average, it takes 5-10 years from
time of initial HIV infection to
become ill or have symptoms
CD4 count is best way to estimate
degree of immune suppression
If CD4 testing is not available, TLC
and WHO Clinical Staging can be
used to evaluate immune system
status
31
Thank you!
Questions?
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