Introduction on HIV - Health[e]Foundation

HIV/AIDS and Treatment
Manado, Indonesia
16 november
HIV [e] EDUCATION

HIV is a…
1. DNA-virus
2. RNA-virus
3. Parasite
0% 0% 0%
DNA-virus
RNA-virus
Parasite

HIV
HIV is a RNA-virus.
HIV is an RNA virus which uses DNA for its
replication.
A virus is unable to replicate (reproduce) on its
own and must first infect a living cell in order to
replicate.

HIV has to infect living cells in order
to replicate…
What kind of cells?
1. Erythrocytes
2. Lymphocytes
3. Thrombocytes
0% 0% 0%
Erythrocytes
Lymphocytes
Thrombocytes

The lifecycle of HIV-1…

Cellular CD4 receptor
Human DNA chromosome
CD4 ( T Helper) Cell

Reverse transcriptase
Cellular CD4 receptor
gp41
HIV
HIV RNA chromosome
Human DNA chromosome
CD4 ( T Helper) Cell

1. HIV approaches CD4
cell
4. Fusion of cell and
virus
2. HIV-CD4 interaction
3. Connection gp41

Cellular CD4 receptor
HIV RNA chromosome
Human DNA chromosome
CD4 ( T Helper) Cell

Cellular CD4 receptor
RNA
nucleotides
HIV RNA chromosome
Human DNA chromosome
CD4 ( T Helper) Cell

Reverse transcriptase
Cellular CD4 receptor
RNA
nucleotides
DNA
nucleotides
HIV RNA chromosome
Human DNA chromosome
CD4 ( T Helper) Cell

Reverse transcriptase
Cellular CD4 receptor
HIV RNA chromosome
HIV DNA provirus
Human DNA chromosome
CD4 ( T Helper) Cell

Integrase
Cellular CD4 receptor
Reverse transcriptase
HIV RNA chromosome
HIV DNA provirus
Human DNA chromosome
CD4 ( T Helper) Cell

Reverse transcriptase
Cellular CD4 receptor
HIV RNA chromosome
HIV DNA provirus
Human DNA chromosome
CD4 ( T Helper) Cell

Cellular CD4 receptor
HIV
HIV RNA chromosome
HIV DNA provirus
Human DNA chromosome
CD4 ( T Helper) Cell

Acute HIV-infection

From HIV- exposure at mucosal
surface to spreading to organs….
How long does it take?
1. 10 minutes
2. 1 day
3. 11 days
4. Three months
0% 0% 0% 0%
10 minutes
1 day
11 days
Three months

Day 0
Day 0-2
Exposure to HIV at
mucosal surface (sex)
Virus collected by
dendritic cells, carried
to lymph node
Day 3-11
HIV replicates in
CD4 cells, released
into blood
Day 11 on
Kahn JO, Walker BD. N Engl J
Med. 1998;339:33-39.
Virus spreads to
other organs

29 year old man, no medical history
2 weeks of malaise, myalgia and since a couple days
a rash
Four weeks ago unprotected sex
Complaints of severe fatigue, no weight loss or
mouth sores
1week ago his GP gave him antibiotics with no
effect
Physical exam: temperature of 38.3 C, diffuse
adenopathy, maculopapular rash

Rash

Test results
HIV RNA: 63.700 copies/ml
HIV antibody: negative
What is your diagnosis?
Acute HIV-infection

Primary HIV Infection: Signs &
Symptoms
80-90% of patients will be symptomatic
A mononucleosis-like like illness of non-specific
signs and symptoms
Signs and symptoms typically begin 1-4 weeks
post-exposure
Kahn JO, Walker BD. N Engl J Med. 1998;339:33-39.
Schacker T, et al. Ann Intern Med. 1996;125:257-264.

Primary HIV Infection:
Common Signs & Symptoms
fever
86
lethargy
74
myalgias
rash
headache
pharyngitis
59
57
55
52
N = 160 patients with PHI in
Geneva, Seattle, and Sydney
adenopathy
44
0 10 20 30 40 50 60 70 80 90 100
% of patients
Vanhems P et al. AIDS 2000; 14:0375-0381.

Typical Risk of Unprotected
Exposures
Estimated Average Per Contact Transmission Risk (%)
Shared Needles 0.7%
Occupational Needlestick 0.3 %
Male to female, vaginal sex 0.2%
Female to male, vaginal sex 0.1%
Receptive oral sex with male 0.03%

How long is your diagnostic window?
The current HIV-antibody screening tests are able to
recognise almost 99.5 % of HIV– infections……
A. 2 weeks
B. 1 month
C. 3 months
D. 1 year
….after primary HIV infection
0% 0% 0% 0%
2 weeks
1 month
3 months
1 year
90

How long is your diagnostic
window?
The current HIV-antibody screening tests are able
to recognise almost 99.5% of HIV-infections…
A. 2 weeks
B. 1 month
C. 3 months
D. 1 year
…..after primary infection with HIV

Typical Course of Primary HIV
HIV RNA
1 mil
100,000
10,000
1,000
100
10
Exposure
HIV
RNA
Symptoms
Ab
+
_
HIV-1 Antibodies
0 3 14 21 28 35
Days

HIV-markers and disease
progression

HIV Disease Progression
Progression can be monitored by:
Clinical markers:
HIV/AIDS-related conditions
Laboratory markers
Increase in blood virus load
Decrease in CD4 cell count

CD4 Count, Viral Load, and Clinical Course
Primary
Infection
Seroconversion
Plasma HIV RNA
10.000.000
1.000.000
100.000
10.000
1.000
100
10
Plasma RNA Copies
CD4 Cells
Intermediate Stage
AIDS
CD4 Cell Count
1,000
500
1
4-8 Weeks Up to 12 Years 2-3 Years

HIV Infection is characterized by a steady
decline in the number of CD4 cells
Acute
Infection
CD4 Cell Count (cells/mm³)
1,000
500
200
Asymptomatic HIV Infection AIDS
CD4 cell count
high risk of opportunistic infections
4-8 Weeks Up to 12 Years 2-3 Years
Time

Association between opportunistic
infections and CD4 + -lymphocyte count
CD4 + -lymphocyte count
(cells/µl)
400
300
200
100
50
Herpes Zoster
Tuberculosis
Oral candidiasis
time
Pneumocystis carinii pneumonia
Esophageal candidiasis
Toxoplasmosis, cryptococcosis
Mycobacterium avium complex
Cryptosporidiosis, PML

Antiretroviral therapy

What is antiretroviral therapy?
ART Antiretroviral
Therapy
ARV Antiretroviral
cART
combination
Antiretroviral
Therapy
HAART Highly
Active
Antiretroviral
Therapy

What kind of classes do we have?
NRTI’s
NNRTI’s
PI’s
(Entry inhibitors)
(Fusion inhibitors)
(Integrase inhibitors)

Available FDA approved drugs
Classes
NRTIs
NNRTI
Protease inhibitors
AZT
DDI
DDC
D4T
3TC
ABC
AZT/3-TC
ZT/3TC/ABC
TDF
FTC
3TC/ABC
TDF/FTC
NVP
Etravirine
EFV
Fusion inhibitors
Enfuvirtide
CCR5 antagonist
Maraviroc
Integrase inhibitor
Raltegravir
Saquinavir
Darunavir
Indinavir
Nelfinavir
Amprenavir
Lopinavir/rtv
Atazanavir
Fosamprenavi
Tipranavir

PI
NRTI NRTI +
or
(the “NRTI backbone”)
NNRTI

Combination of at least 3 drugs, usually:
2 NRTIs (the “NRTI backbone”), plus:
1 NNRTI or 1-2 PIs
Therapy with only one or two agents allows
HIV to overcome therapy through resistance
mutations

Goals of HAART
Prolong life and improve quality of life
Achieve maximal suppression of HIV
Low (undetectable) viral load
Reverse immune system damage
Increase CD 4 -count

Initiation of Antiretroviral
Therapy: Key Considerations
Symptoms & Opportunistic Infections
CD4 count
Anticipated Adherence - patient ‘readiness’

CDC A:
Asymtomatic
Lymphaden.
B:
Symptomatic
C:
AIDS defining
illness
1
>500 CD4
Deferal
treatment
start
treatment
Start
treatment
2
200-499 CD4
200-350 start
treatment
Start
treatment
Start
treatment
3

When to start?
DHHS Guidelines 2008 update january

Male 28 years, HIV+
CD4 cell count: 150/µl, retrosternal pain
1. Yes
2. No
Start HAART?
0%
0%
Yes
No
90

Male 28 years, HIV+
CD4 cell count: 370/µl, retrosternal pain
Start HAART?
1. Yes
2. No
0%
0%
Yes
No
90

Male 42 years, HIV+, dry cough since three
weeks, breathing frequency 40/min
CD4 cell count: 170/µl
X-thorax:
Start HAART?
1. Yes
2. No
0%
0%
Yes
No
90

Male 42 years, HIV+, dry cough since three
weeks, breathing frequency 40/min
CD4 cell count: 220/µl
X-thorax:
Start HAART?
1. Yes
2. No
0%
0%
Yes
No
90

Male 42 years, HIV+, dry cough since three weeks,
breathing frequency 40/min, CD4 cell count: 170/µl
X-thorax:
When to start HAART?
1. Now
2. 2-8 Weeks
3. 3 months
0% 0% 0%
Now
2-8 Weeks
3 months
90

Woman 34 years old; HIV+, Unexplained weight
loss; 66 kg 46 kg, CD4 cell count: 410/µl
Start HAART?
1. Yes
2. No
0%
0%
Yes
No
90

The treatment of patients with
symptomatic conditions (CDC B)
or an AIDS defining illness (CDC C)
should not depend on a CD4 cell
count!

Pfffffffff
finished!