This powerpoint, deals with HIV pathophysiology, signs and symptoms, mode of transmission and diagnostic parameters.
Purely based on clinical pharmacist perspective.
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
HIV Pathophysiology, by Dr. Vishnu
1. HIV PATHOPHYSIOLOGY: ALL
YOU NEED TO KNOW
Dr. Vishnu R Nair, Pharm-D, RPh,
Dip. (Nutrition),
Assistant Professor (Dept. of
Pharmacy Practice),
NIMS Institute of Pharmacy.
HIV: THE SILENT KILLER
2. DEFINITIONS:
HIV (Human Immunodeficiency Virus): Virus, that
attacks cells which help in fighting infections
reduces immunity of the affected person
Refer: https://www.hiv.gov/hiv-
basics/overview/about-hiv-and-aids/what-are-hiv-
and-aids
AIDS (Acquired Immunodeficiency Syndrome): Late
stage of HIV infection, that occurs when the body’s
immune system is badly damaged due to HIV.
EPIDEMIOLOGICAL STATISTICS:
38 million people are living with HIV worldwide
African region remains worst affected (1 out of
every 25 people have HIV)
Refer: https://www.who.int/gho/hiv/en/
In India:
a.2.1 million people living with HIV
b.Third largest HIV epidemic in the world
c.Prevalence age of disease: 15-49 years
3. d.50% of HIV cases in India concentrated in
Maharashtra, Tamil Nadu & Andhra Pradesh
(mostly contracted heterosexually)
e.8% of HIV cases in India concentrated in
North-East (Manipur) [among intravenous drug
abusers].
f.Refer: https://www.avert.org/professionals/hiv-
around-world/asia-pacific/india
ETIOLOGIC AGENT:
STRUCTURE OF HIV VIRUS.
4. AIDS caused by a HIV virus
RNA virus in nature (retrovirus)
ROUTES OF TRANSMISSION:
1.Sexual transmission:
Constitutes 75% of all HIV transmissions
Other STDs (gonorrhea, chlamydial infections)
help in HIV spreading
Transmission from male-to-male & male-to- female
more potent than female-to-male.
2.Transmission via blood & blood products:
Occurs due to:
a.Intravenous drug abusers (sharing needles,
syringes)
b.Haemophiliac patients receive large
amounts of blood from multiple donors high
risk!
c.Blood transfusions (if blood/ blood product is
infected with HIV)
5. 3.Vertical transmission:
Also known as perinatal transmission
Occurs either via:
a.Mother to fetus transmission
b.Through breast milk.
4. Occupational transmission:
Improper disposal of biological wastes
renders health-care professionals at high risk of
HIV!
5. Transmission by other body fluids:
Saliva, tears, sweat, urine, breast milk, CSF, etc...
6. PATHOGENESIS:
Major principle: Depletion of CD4+ T-cells
(Helper T-cells) results in profound
immunosuppression!!
Explained via the following steps:
A.Selective tropism for CD4+ molecule
receptor
B.Internalisation
C.Uncoating & viral DNA formation
D.Viral integration
E.Viral replication
F.Latent period & immune attack
G.CD4+ T-cell destruction
H.Viral dissemination
I.Impact of HIV infection on other immune
cells.
7. 1. Selective tropism for CD4+ molecule receptor:
HIV enters into body uses its gp120
envelope to bind to CD4+ T-cell
Tropism means affinity
In other words, HIV has affinity for
CD4+ T-cell binds to it.
2. Internalization:
HIV binds to CD4+ T-cell receptor surface
For entering into cell membrane HIV uses
CCR (Chemokine coreceptor)
3. Uncoating & viral DNA formation:
Once virus enters into T-cell cytoplasm
Viral RNA gets converted into DNA, using
enzyme reverse transcriptase
8. ss-DNA formed
ss-DNA forms ds-DNA using enzyme DNA
polymerase
This viral DNA undergoes frequent mutations
Thus, HIV is incurable (less response to anti-
retroviral therapy)!!
4. Viral integration:
Viral DNA in cytoplasm
Enters into nucleus of host T-cell, using
enzyme integrase
Viral particle at this stage provirus (stage of
virus, where it enters into T-cell DNA, and
becomes part of host cell DNA).
9. 5. Viral replication:
HIV provirus
Part of host cell DNA
Host cell DNA transcripts for viral RNA, using tat
gene
Viral particles multiply, with the help of:
RNA viral particles fill cytoplasm of CD4+ T-
cell
acquire protein coating
Released cytokines cause spread of infection
to other body sites (e.g., CNS infection caused
by TNF-α)
IL-4, IL-5, IL-6,
IL-10
(produced by
TH2 cells)
IL-2, Interferon-
alpha (produced
by TH1 cells)
10. 6. Latent period & immune attack:
Virus may remain inactive in the
infected T-cell for long time periods
(known as latent period)
During latent period immune
system gets activated
Antibodies, macrophages, CD4+ &
CD8+ T- cells try to eliminate virus
in vain!!!
7. CD4+ T-cell destruction:
Viral particles inside cell form buds
on the cell-wall of host cell
Through buds virus detaches from
host cell causes damage to cell
membrane death of host cell!
11. 8. Viral dissemination:
Once host cell is killed (broken up) viral
particles get released into blood spread to
all body parts & infect more CD4+ T-cells!
Causes viraemia!
HIV through circulation enters lymphoid
tissues (lymph nodes, spleen) multiplies
further
Finally, lymphoid tissues become
reservoir of virus!
9. Impact of HIV infection on other immune cells:
Effects include:
Immune system
parameter
Impact of HIV infection
Macrophages Become reservoir of HIV
Infection
Dendritic
follicular cells of
lymph node
HIV causes massive
enlargement of follicle centres
causes lymphadenopathy
12. B-cells
CD4+ T-cells activate B-
cells
Reduction in T-cells (due to
HIV infection)
causes reduction in B-
cells
NK cells Reduced Helper T-cells
reduced cytokine production
reduces NK cells
CD8+ T-cells Increased.
Net effect of HIV on immune system: Profound
immunosuppression!!!
Severe immunosuppression makes victim
vulnerable to opportunistic infections &
tumours eventual death!!!
13. CLINICAL MANIFESTATIONS
OF HIV INFECTION:
Manifestation Important catchpoints
Wasting syndrome
Involuntary loss of body weight
(>10%)
Reasons include:
1.Malnutrition
2.Hyper-metabolism
3.Malabsorption
4.Anorexia
5.Complications of multiple
opportunistic infections.
Persistent
generalized
lymphadenopathy
Enlarged lymph nodes
Damage to lymph nodes
increased risk of opportunistic
infections
GI system
Due to opportunistic infections:
a)Chronic watery/bloody diarrhoea
b)Oral candidiasis
c)Anorexia
d)Mucosal ulcers
e)Abdominal pain
In advanced stage/AIDS:
a) GI tumors (Kaposi’s sarcoma)
18. For further reference check on the
following links:
1.https://www.youtube.com/watch?v=5g1ijp
BI6Dk
2.https://www.youtube.com/watch?v=Qm2
wV- wCCOI
3.https://www.youtube.com/watch?v=8sipX8
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THANK YOU!!!