Download Physiological Factors in ill health (HIV / AIDS)

AIDS
• Acquired immune deficiency syndrome
• A group of illnesses resulting from immune system
damage caused by infection with HIV.
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Human Immunodeficiency Virus (HIV)
structure.
• The outer shell of the virus is known as the viral
envelope.
• Embedded in the viral envelope is a complex protein
known as env, which consists of an outer protruding
cap glycoprotein (gp) 120, and a stem gp41.
• Within the viral envelope is an HIV protein called p17
(matrix), and within this is the viral core or capsid,
which is made of another viral protein p24 (core
antigen).
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• The major elements contained within the viral core are:
- two single strands of HIV RNA
- a protein p7 (nucleocapsid)
- three enzyme proteins
p51 (reverse transcriptase)
p11 (protease)
p32 (integrase)
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HIV Replication
• HIV has a diameter of 1/10,000 of a millimetre.
• HIV belongs to class of viruses called retroviruses
• These have genes composed of ribonucleic acid (RNA)
molecules.
• Retroviruses, like all viruses, can only replicate within a
living host cell because they contain only RNA and
they do not contain DNA.
• Retroviruses use RNA as a template to make DNA.
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• Infection begins when HIV particle encounters a
T-Helper cell with a surface molecule called CD4.
• Virus particle uses gp120 to attach itself to the cell
membrane
• Then enters the cell.
• Within cell, virus particle releases its RNA
• The enzyme reverse transcriptase then converts the
viral RNA into DNA.
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• New HIV DNA moves into the cell's nucleus
• With the help of the enzyme integrase its then inserted
into the host cells DNA.
• Once in the cell's genes HIV DNA is called a provirus.
• The HIV provirus is then replicated by the host cell,
which can then release new infectious virus particles.
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Origins of HIV
1). Simian Virus
• HIV part of family of viruses – Lentivirusus
• Lentiviruses found mainly in non human primates
• Primate Lentiviruses collectively known as
Simian (monkey) viruses (SIV)
• Simian immunodeficiency virus (SIV)
• HIV accepted as a descendant of SIV
HIV – 1 corresponds to SIV in green monkey
HIV – 2 corresponds to SIV in chimpanzee
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2). Crossed species?
• Virus crossed from chimps to humans
• Zoonosis – transfer of virus from animals to humans
e.g.
• Eating chimp for food
• Iatrogenic transfer (via medical experiments)
- Oral polio vaccine Chat. Grown in chimp kidney cells
in Congo. Contamination of vaccine with chimp SIV
- Vaccine given to 1x106 people in Belgium Congo,
Ruanda and Urundi
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Transmission of HIV
• Cannot survive dry conditions.
• No air transmission, body fluids only
• Blood Products
• Drug Misuse
• Sexual Transmission
• Mother to child transmision
- pregnancy
- labour and delivery
- breastfeeding
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HIV Subtypes
• 2 types of HIV:
- HIV-I, predominant type
- HIV-2, less easily transmitted
• Both HIV-I and HIV-2 transmitted by:
- sexual contact, through blood, and from mother
to child
• They appear to cause clinically indistinguishable AIDS.
• However, HIV-2 is less easily transmitted
• Period between initial infection and illness is longer in
the case of HIV-2.
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• HIV-I mutates readily
• HIV-I has many different strains
• Strains classified into 2 groups:
- Group M - 10 distinct subtypes (A-J)
- Group O - other subtypes
• Subtypes differ in:
1. Mode of transmission
subtype B – homosexual contact / intravenous drug use
subtype E / C – heterosexual transmission
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2.
Genetic composition
3.
Subtype distribution
B;
Americas, Japan, Australia, Europe
A,D;
Africa
C;
South Africa, India
E;
Central Africa, Thailand, Asia
F;
Brazil, Romania
G,H;
Russia, Central Africa
I;
Cyprus
O;
Cameroon
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The Groups of Antiretroviral Drugs
• There are three main groups of anti-HIV drugs.
• Each of these groups attacks HIV in a different way.
- Reverse Transcriptase Inhibitors
- Protease Inhibitors
- Fusion or Entry Inhibitors
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Reverse Transcriptase Inhibitors
• 2 Types:
(a) Nucleoside Reverse Transcriptase Inhibitors
(b) Non-Nucleoside Reverse Transcriptase Inhibitors
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Nucleoside Reverse Transcriptase Inhibitors
• First type of drug available to treat HIV infection (1987)
• HIV needs enzyme reverse transcriptase to be able
to infect healthy cells and reproduce itself in a person's
body.
NRTIs:
- inhibit reverse transcriptase.
- drugs slow down the production of the reverse
transcriptase enzyme
- make HIV unable to infect cells and duplicate itself.
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Non Nucleoside Reverse Transcriptase Inhibitors
• Drugs started to be approved in 1997
• These drugs also stops HIV from infecting cells by
intervening with the trancriptase of the virus.
• The non-nucleoside drugs work slightly differently from
the nucleoside analogues
• They bind in a different way to the cell's reverse
transcriptase.
• The non-nucleoside drugs block the duplication and the
spread of the HIV.
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Protease Inhibitors
• The third type of antiretrovirals.
• Inhibit protease.
• Almost every living cell contains protease.
• Protease is a digestive enzyme that breaks down
protein and is one of the many enzymes that HIV uses
to reproduce itself.
• The protease in HIV attacks the long healthy chains of
enzymes and proteins in the cells and cuts them into
smaller pieces.
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• The infected smaller pieces of proteins and enzymes
continue to infect new cells.
• Protease inhibitors (PI) take effect before the protease
in HIV has the chance to break down the protein and
enzymes.
• The PI slow down the duplication of the virus and so
prevent infection of new cells.
• The NRTIs and NNRTIs only have an effect on newly
infected cells.
• PI are able to slow the process of immature noninfectious virus becoming mature and infectious.
• PI also work in cells that have been infected for a long
time, by slowing down the reproduction of the virus.
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Fusion or Entry Inhibitors
• Fourth group of antiretrovirals called Fusion or Entry
Inhibitors.
• These drugs have yet to be approved and are currently
going through clinical trials in the UK and the USA.
• The surface of HIV carries proteins called gp41 and
gp120.
• These are the proteins, which allow HIV to attach itself
to, and enter into cells.
• By blocking one of these proteins, fusion inhibitors slow
down the reproduction of the virus.
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• For example, T-20, the fusion inhibitor that is closest to
approval, sticks to the protein gp41.
• The T-20 fusion inhibitor differs from the other
antiretrovirals in that it needs to be injected.
• T-20 is a protein and cannot be taken orally, since it
would be digested in the stomach.
• It is hoped that the results from the T-20 trials across
the USA and Europe will completed and returned to the
Federal Drug Agency (FDA) by autumn 2002.
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Progression of HIV
• Acute retroviral syndrome – flu, cough, rash
• Asymptomatic phase – 5-6 years
• Symptomatic phase – AIDS
• Opportunistic infection – Pneumonia, cancers
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