Virology and

Pathogenesis of HIV
Infection
 Session Objectives
By the end of the training the participants will be able to
 Describe what is HIV and AIDS

 Describe the routes of HIV transmission and it’s

preventive measures

 Understand the progression of HIV infection and it’s

correlation with Immune response of the body

 Understand the basics of Anti Retroviral Therapy (ART)

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 What is HIV?
 HIV stands for Human Immunodeficiency Virus

 HIV attaches to the White Blood Cells in the body and slowly
kills them

 HIV cannot be destroyed by the body - an infected person

carries HIV for life

 There are medicines (Anti Retro Viral Treatment- ART)

available, which can prolong life if taken regularly

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 What is AIDS?
Acquired Immunodeficiency Syndrome

A Acquired (not inherited but contracted after birth)

I Immune (weakens the immune system)

D Deficiency (of certain white blood cells –Helper T4

lymphocytes in the immune system)

S Syndrome (a group of symptoms or illnesses as a result of

HIV infection)
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What is the difference between
HIV and AIDS?

 HIV is a virus and AIDS is a disease

 HIV infection is merely the presence of virus in the body

 AIDS is deficiency in the body’s defence mechanism or

immune system due to the presence of HIV

 HIV infection leads to AIDS, depending on the body’s

defence mechanism

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 Basics of HIV
 The human immunodeficiency viruses 1 and 2 (HIV-1, HIV-2)
originated from the simian immunodeficiency viruses (SIVs) of
primates
 HIV-1 was first isolated in 1983 and HIV-2 in 1986 and they
represent two different epidemics
 The SIV of chimpanzees (SIVcpz) gave rise to HIV-1 in
humans, and the SIV of the sooty mangabey monkey (SIVsm)
to HIV-2 in humans

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 Classification of HIV
 The two human immunodeficiency viruses, HIV-1 and HIV-2,
are members of the family of Retroviruses, in the genus of
Lentiviruses
HIV Classifications

M N O
Major New Outlier

HIV-1 Sub types: A through K, excluding I

Predominant sub type in India:HIV-1M:C

 In India HIV -1 (Subtype C) is predominant.

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 Structure of HIV-1

Approximately 100 nm in diameter.

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 Structure of HIV
 It has a lipid envelope, in gp 36 in case of HIV-2
which glycoprotien gp41 is
embedded.
 Gp36 in case of HIV 2.
 Glycoprotien gp120 is
attached.

These two viral proteins are responsible for attachment to

the host cell and are encoded by the env gene.

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 Structure of HIV
 Inside envelope is a
nucleocapsid (p17) which
surrounds a central core of
protein, p24.
 Within this core, are two
copies of single-stranded
RNA (the virus genome).
 The virus also contains
three enzymes –
 Reverse transcriptase
 Integrase and
 Protease
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Routes of Transmission of HIV

Infected
blood/blood
products
 Prevention of HIV Transmission

 Sexual Transmission: Safe sexual practices, using condoms

etc.
 Transmission through blood and blood products:
 Ensure screened blood and blood products are used (Safe
blood and blood products, rationale use of blood)
 Through needles (IDUs), needle stick and occupational
exposure:
 Standard work precautions and PEP (safe needles including
for IDUs)
 HIV positive mother to the baby: PPTCT program

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HIV is NOT transmitted by…

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 Who is at Risk…?
 Anybody is at risk of HIV if infected fluids from an HIV-positive
person enters their body through open sores, cut or any other
route.
 HIV does not exclusively affect certain groups of people.
 If people living with HIV are on antiretroviral treatment and
have an undetectable viral load, the risk of HIV transmission
is greatly reduced

One cannot tell if another person is living with HIV just by looking
at them. People living with HIV are the same as everyone else

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 Quiz????

Can you tell if the person is living with HIV just by looking at
them?

People living with HIV are the same as everyone else

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 Susceptibility of HIV
 HIV is a highly fragile virus. Needs living cells to survive.
The methods used for sterilization and disinfection to kill the
virus.
 Autoclaving at 121°C at 15psi pressure for 20 minutes
 Dry heat 160°C for 1 hr. (holding time)
 Boiling for 20 minutes
 1% Sodium hypochlorite
 Ethanol 70%
 Povidone iodine (PVI) – 10%
 Glutaraldehyde (activated) 2% for 30 minutes

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 Susceptibility of HIV
• HIV is stable for several hours at a pH between 3 and 10
• HIV is stable over several hours against the influence of physical
conditions like ultraviolet light, gamma irradiation or ultrasonic waves
• The half-life (t/2) of HIV in solution is approximately 30 min at 56 °C,
1 min at 60 °C and less than 1sec at temperatures above 65 °C.
• Treatment of lyophilised HIV preparations at 100 °C (dry heat) for 10
min inactivates HIV completely

Transfus Med Hemother 2016;43:203-222 https://doi.org/10.1159/000445852

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 Susceptibility of HIV

• At lower temperatures HIV is relatively stable: t/2 is at 20 °C

approximately 9 h, at 4 °C several months and below −70 °C
indefinitely.
• Half-Life Time in Blood and Plasma at body temperature of HIV is
approximately 2 days and at 4 °C approximately 1 month.

Transfus Med Hemother 2016;43:203-222 https://doi.org/10.1159/000445852

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 Life Cycle of HIV

CD4 cell

HIV
Step One: Attachment
Life Cycle of HIV- Attachment

CD4 Binding

Co-receptor
(CCR5 or CXCR4)

CD4

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 Life Cycle of HIV- Fusion

FUSION
Life Cycle of HIV- Virion Entry

Virion entry
Life Cycle of HIV- Reverse
Transcription of Viral RNA

HIV RNA
Life Cycle of HIV- Formation of HIV
DNA

Reverse transcription

HIV DNA
Life Cycle of HIV- Translocation
of HIV DNA to Nucleus

Translocation to nucleus
Life Cycle of HIV- Integration
of HIV DNA into Host DNA

Integration
Life Cycle of HIV- Proviral DNA
Expression

Transcription / Translation
of HIV mRNA / polyprotein
Life Cycle of HIV- Release of HIV

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 HIV vs. Immune System (1/2)
 White blood cells (WBCs) are the most important part of
immune system.
 When HIV enters the body, CD4 - T lymphocyte (type of
WBCs) are attacked.
 The virus multiplies inside CD4 cells and infects other CD4
cells.
 Each generation of viruses is slightly different.
 This constant evolution helps HIV keep one step ahead of
the immune system. Immune cells can only look for viruses
that resemble the previous generation of HIV, so the virus
constantly ‘escapes’ the immune system.

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 HIV vs. Immune System (2/2)
 CD4 T-cells gradually decline in number.

 This is because they are killed by HIV and also because

they are over-activated and this leads to increased T-cell
death.

 Various opportunistic infections such

as Pneumocystis pneumonia and Candida infection develop
when the CD4 cell count falls.

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Typical HIV-1 infection: Lab
Markers for diagnosis and
monitoring
 Window period
 Time taken from day of HIV infection to
positive HIV antibody test (ELISA/RAPID)

 Most HIV infected patients seroconvert

within six months

 HIV seroconversion is the time when a

person first develops antibodies for HIV.
 During this period, an HIV antibody
test will still be negative. The word
just means that your serological
status is converting from being HIV
antibody negative to HIV antibody
positive.

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 Pathogenesis of HIV Infection
 In the absence of antiretroviral
therapy, the natural course of the
disease is generally as follows:
 Primary Infection
 Asymptomatic Phase
 Symptomatic Phase
 In primary HIV infection, only about
50% of infected individuals are
symptomatic with fever and
lymphadenopathy.
 After seroconversion (when anti-HIV
antibodies are detectable), there
follows an asymptomatic period of
2-15 years.
 During this period, viral replication
continues at a high rate 34
 Pathology of HIV Infection
 During primary HIV infection
 Virus is easy to isolate
 CD4 lymphocyte count drops
rapidly for a short period, before
recovering to almost normal
levels
 Asymptomatic phase
 Viruses evolve into a more
heterogeneous population, and
are less easy to isolate
 There is a steady decline in the
CD4 count.
 Symptomatic Phase
 CD4 count drops quickly as the
patient approaches end-stage
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disease.
 Rate of progression of HIV
infection without ART
Based on kinetics of virologic and immunologic events three
dominant patterns of HIV disease are described.

1.80-90% of HIV infected are typical progressors survival time

appx. 11 years.

2.5-10% are “rapid progressors” with median survival time of

3-4 years.

3.7-10% of HIV-infected individuals do not experience

disease progression for extended period of time and are
called “long term non progressors” (LTNPs).
 Earlier it was called
Pneumocystis
carinii pneumonia

Pneumocystis jiroveci Pneumonia

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 WHO staging system for HIV
infection in adults and
adolescents >13 years of age
Clinical Stage Signs & Symptom Performance Scale
Clinical stage I Asymptomatic Asymptomatic,
Persistent generalised lymphadenopathy normal activity
Clinical stage II Weight loss, <10% of body weight. muco- Symptomatic,
cutaneous manifestations , Recurrent upper normal activity.
respiratory tract infections

Clinical stage III Weight loss, >10% of body weight. In bed more than
Unexplained chronic diarrhoea, prolonged normal but less
fever , Oral candidiasis than half of normal
daytime during the
previous month.
Clinical stage IV HIV wasting syndrome In bed more than
Toxoplasmosis of the brain. normal but more
Cryptococcosis, extra pulmonary TB etc than half of normal
daytime during the
previous month 38
 Detection of HIV Infection

 Clinical symptoms of HIV infection are not characteristic to

enable diagnosis
– Acute infection may be asymptomatic
– Infection may be/is silent until last stages (AIDS)
 Only way to diagnose HIV infection is by laboratory testing for
specific antibodies and/or the structural components of HIV

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 Anti retro viral therapy (ART)

 Standard antiretroviral therapy (ART) consists of the

combination of antiretroviral (ARV) drugs to maximally suppress
the HIV virus and stop the progression of HIV disease.

 ART drugs act on various stages of replication of the virus in

the body and interrupt the process of viral replication.

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 Life Cycle and ARTs site of
action
Fusion/Entry
Inhibitors
Protease
Inhibitors

Reverse
Transcriptase
Inhibitors
Integration
Inhibitors
 ART works: Progression to
AIDS/Death
30
% Patients Progressing

25 Dual
No Therapy
Therapy
20 Mono-
Therapy
15

1
0 Triple Therapy
5

0
1 2 3 4 5 6 7 8 9 10 11 12 13

Months
JAMA 1998
 Key points
 HIV is a virus whereas AIDS is a disease
 All AIDS patients have HIV infection, BUT not all HIV infected
patients have AIDS
 Infection is primarily transmitted through four routes
 Everyone is at a risk of acquiring the infection
 HIV is a very fragile virus and gets killed easily
 It attaches to the CD4 T lymphocytes and destroys them
 In the absence of ART, CD4 cell count falls, PLHIV’s immunity
is compromised and they develop opportunistic infections
 Only way to diagnose HIV infection is by laboratory tests

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Thank You

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