HIV / AIDS
Kolářová M., EPI
Autumn 2015
Fosfolipid membrane
gp120 surface glykoprotein
gp 41 transmembrane
glykoprotein
p 17M protein - matrix
p 24 protein – nucleocapsid core
RNA genome
reverzní transkriptáza
p 7, p 9
proteiny on the nucleic acide
HIV/AIDS
HIV - Human Immunodeficiency Virus is classed with the
Retroviridae family, Lentivirus genus. HIV occurs in two types:
HIV - 1 and HIV - 2. Both types have similar epidemiological
features, but different serological response and geographic
distribution. .
Only infected man is the source of infection, in either the sick with manifestations of
AIDS or a latent infection, (ARC - AIDS-Related Complex, PGL - Persistent
Generalised Lymphadenopathy) or a symptomless carrier.
Blood - borne By blood derivates and HIV- contaminated blood.
Use of contaminated needles and syringes in drug administration.
Sexually-transmitted, when injury of the mucosa and bleeding occur.
Sexually transmitted Through sperma, vaginal secreta in homo and heterosexual
intercourse.
From mother to child (15 to 30 %) Vertical transmission - prenatally, perinatally or
possibly through the mother´s milk.
General.
General
The source of
infection
Route of
transmission
Susceptibility
Etiology:
Preventive measures:
Health education promoting a responsible approach to sex - use of condoms.
To prevent contamination of blood tins and derivates.
Supporting the programme of taking/giving needles and syringes from/to intravenous drug addicts.
Virus classification
Group: Group VI (ssRNART)
Family: Retroviridae
Genus: Lentivirus
Species:Human immunodeficiency virus1
Species:Human immunodeficiency virus 2
Diagram of HIV is different in structure from other
retroviruses.
It is about 120 nm in diameter (120 billionths of a
meter; around 60 times smaller than a red blood
cell) and roughly spherical.
It is composed:
of two copies of positive single-stranded RNA that codes
for the virus's nine genes enclosed by a conical capsid
composed of 2,000 copies of the viral protein p24.
The single-stranded RNA is tightly bound to nucleocapsid
proteins, p7 and enzymes needed for the development of
the virion such as:
•reverse transcriptase, * proteases, * ribonuclease and
* integrase.
A matrix composed of the viral protein p17 surrounds the
capsid ensuring the integrity of the virion particle.
This is, in turn, surrounded by the viral envelope
which is composed of two layers of fatty molecules
called phospholipids taken from the membrane of a
human cell when a newly formed virus particle buds
from the cell.
Embedded in the viral envelope are proteins from
the host cell and about 70 copies of a complex HIV
protein that protrudes through the surface of the
virus particle.
This protein, known as Env, consists of a cap made
of three molecules called glycoprotein (gp) 120, and
a stem consisting of three gp41 molecules that
anchor the structure into the viral envelope.
This glycoprotein complex enables the virus to
attach to and fuse with target cells to initiate the
infectious cycle.
Both these surface proteins, especially gp120, have
been considered as targets of future treatments or
vaccines against HIV.
Of the nine genes that are encoded within the RNA
genome, three of these genes, gag, pol, and env, contain
information needed to make the structural proteins for new
virus particles. env, for example, codes for a protein called
gp160 that is broken down by a viral enzyme to form gp120
and gp41.
The six remaining genes, tat, rev, nef, vif, vpr, and vpu (or
vpx in the case of HIV-2), are regulatory genes for proteins
that control the ability of HIV to infect cells, produce new
copies of virus (replicate), or cause disease.
HIV primarily infects vital cells in the human immune
system such as helper T cells (specifically CD4+ T cells),
macrophages and dendritic cells.
HIV infection leads to low levels of CD4+ T cells through
three main mechanisms:
•firstly, direct viral killing of infected cells;
•secondly, increased rates of apoptosis in infected cells;
•and thirdly, killing of infected CD4+ T cells by CD8
cytotoxic lymphocytes that recognize infected cells.
When CD4+ T cell numbers decline below a critical level,
cell-mediated immunity is lost, and the body becomes
progressively more susceptible to opportunistic infections.
The AIDS epidemic was discovered June 5, 1981, when
the U.S. Centers for Disease Control and Prevention (CDC)
reported a cluster of Pneumocystis carinii pneumonia (now
classified as Pneumocystis jiroveci pneumonia) in five
homosexual men in Los Angeles.
The disease was originally dubbed GRID, or Gay-Related
Immune Deficiency, but health authorities soon realized
that nearly half of the people identified with the syndrome
were not homosexual men.
In 1982, the CDC introduced the term AIDS to describe the
newly recognized syndrome, though it was still casually
referred to as GRID.
In 1983, scientists led by Luc Montagnier at the Pasteur
Institute in France first discovered the virus that causes
AIDS. They called it lymphadenopathy-associated virus
(LAV).
A year later a team led by Robert Gallo of the United States
confirmed the discovery of the virus, but they renamed it
human T lymphotropic virus type III (HTLV-III).
The dual discovery led to considerable scientific
disagreement, and it was not until President Mitterrand of
France and President Reagan of the USA met that the
major issues were resolved.
In 1986, both the French and the U.S. names for the virus
itself were dropped in favour of the new term, human
immunodeficiency virus (HIV).
In 2005 alone, AIDS claimed an estimated 2.4–3.3
million lives, of which more than 570,000 were
children.
It is estimated that about 0.6% of the world's living
population is infected with HIV.
A third of these deaths are occurring in sub-Saharan
Africa, retarding economic growth and increasing
poverty.
According to current estimates, HIV is set to infect
90 million people in Africa, resulting in a minimum
estimate of 18 million orphans.
Subtypes:
HIV 1 - group“M” (major) – subtypes A, B, C, D, E, F, G, H, I,…
(expected other)
Subtypes:
A – West and Middle Africa
B – Europe, North and sud America, Thailand
C – Sud Africa, Indie
D – Middle Africa
E – Middle Africa, Thailand, Indie
F – Brazilie, Romania, Zair
G – Middle Africa
H – Gabun, Zair
I – Africa
Subtypes:
- group „O“ (outlier) – subtyp O, …
-(expected other)
O – Gabun,
- group „N“ (novel)
N – Africa
AIDS – Acquired ImmunoDeficiency Syndrome
SIDA – Syndrome d´ImmunoDeficience Acquise
SPID – Syndrom Priobretěnovo ImunoDeficita
HIV - Human Immunodeficiency Virus
Human immunodeficiency virus (HIV) is a retrovirus
that causes acquired immunodeficiency syndrome (AIDS) =
a condition in humans in which the immune system begins
to fail, leading to life-threatening opportunistic infections.
Previous names for the virus include
human T-lymphotropic virus-III (HTLV-III),
lymphadenopathy-associated virus (LAV),
and AIDS-associated retrovirus (ARV)
HIV infection in humans is now pandemic.
As of January 2006, the Joint United Nations Programme
on HIV/AIDS (UNAIDS) and the World Health Organization
(WHO) estimate that
AIDS has killed more than 25 million people since it was
first recognized on December 1, 1981, making it one of the
most destructive pandemics in recorded history.
Antiretroviral treatment reduces both the mortality
and the morbidity of HIV infection, but routine access
to antiretroviral medication is not available in all
countries.
If untreated, eventually most HIV-infected individuals
develop AIDS (Acquired Immunodeficiency
Syndrome) and die; however about one in ten
remain healthy for many years, with no noticeable
symptoms.
Treatment with anti-retrovirals, where available,
increases the life expectancy of people infected
with HIV. It is hoped that current and future
treatments may allow HIV-infected individuals to
achieve a life expectancy approaching that of the
general public
• Upon entry of the target cell, the viral RNA genome is
converted to double-stranded DNA by a virally encoded
reverse transcriptase that is present in the virus particle.
• This viral DNA is then integrated into the cellular DNA by
a virally encoded integrase so that the genome can be
transcribed.
• Once the virus has infected the cell, two pathways are
possible:
• either the virus becomes latent and the infected cell
continues to function,
• or the virus becomes active and replicates, and a large
number of virus particles are liberated that can then
infect other cells.
Two species of HIV infect humans: HIV-1 and HIV-2.
HIV-1 is thought to have originated in southern Cameroon
after jumping from wild chimpanzees (Pan troglodytes
troglodytes) to humans during the twentieth century.
HIV-2 may have originated from the Sooty Mangabey
(Cercocebus atys), an Old World monkey of GuineaBissau,
Gabon, and Cameroon.
HIV-1 is more virulent. It is easily transmitted and is the
cause of the majority of HIV infections globally.
HIV-2 is less transmittable and is largely confined to West
Africa. HIV-1 is the virus that was initially discovered and
termed LAV.
• Three of the earliest known instances of HIV-1
infection are as follows:
• A plasma sample taken in 1959 from an adult male
living in what is now the Democratic Republic of
Congo.
• HIV found in tissue samples from a 15-year-old
African-American teenager who died in St. Louis in
1969.
• HIV found in tissue samples from a Norwegian
sailor who died around 1976.
• Although a variety of theories exist explaining the transfer of HIV
to humans, no single hypothesis is unanimously accepted, and the
topic remains controversial.
• The most widely accepted theory is so called 'Hunter' Theory
according to which transference from chimp to human most likely
occurred when a human was bitten by a chimp or was cut while
butchering one, and the human became infected.
• The London Times published an article in 1987 stating that WHO
suspected some kind of connection with its vaccine program and
AIDS-epidemic. The story was almost entirely based on
statements given by one unnamed WHO advisor. The theory was
supported only by weak circumstantial evidence and is now
disproven by unraveling the genetic code of the virus and finding
out that the virus dates back to the 1930s.
• Transmission
Exposure Route Estimated infections per 10,000 exposures to an
infected source:
• Blood Transfusion 9,000
• Childbirth 2,500
• Needle-sharing injection drug use 67
• Receptive anal intercourse* 50
• Percutaneous needle stick 30
• Receptive penile-vaginal intercourse* 10
• Insertive anal intercourse* 6.5
• Insertive penile-vaginal intercourse* 5
• Receptive fellatio* 1
• Insertive fellatio* 0.5
* assuming no condom use
• Since the beginning of the pandemic, three main
transmission routes for HIV have been identified:
• Sexual route. The majority of HIV infections are acquired
through unprotected sexual relations. Sexual transmission
can occur when infected sexual secretions of one partner
come into contact with the rectal, genital or oral mucous
membranes of another.
Blood or blood product route. This transmission route
can account for infections in intravenous drug
users, hemophiliacs and recipients of blood
transfusions (though most transfusions are checked
for HIV in the developed world) and blood products.
It is also of concern for persons receiving medical
care in regions where there is prevalent
substandard hygiene in the use of injection
equipment, such as the reuse of needles in Third
World countries. HIV can also be spread through
the sharing of leaches.
Health care workers such as nurses, laboratory
workers, and doctors, have also been infected,
although this occurs more rarely.
People who give and receive tattoos, piercings and
scarification procedures can also be at risk of
infection.
Mother-to-child transmission (MTCT). The transmission of
the virus from the mother to the child can occur in utero
during the last weeks of pregnancy and at childbirth. In
the absence of treatment, the transmission rate between
the mother and child is 25%. However, where drug
treatment and Cesarian section are available, this can be
reduced to 1%. Breast feeding also presents a risk of
infection for the baby.
• HIV-2 is transmitted much less frequently by the MTCT
and sexual route than HIV-1.
HIV has been found at low concentrations in the:
saliva,
tears and
urine of infected individuals,
but there are no recorded cases of infection by
these secretions and the potential risk of
transmission is negligible.
The use of physical barriers such as the latex
condom is widely advocated to reduce the sexual
transmission of HIV.
Spermicide, when used alone or with vaginal
contraceptives like a diaphragm, actually increases
the male to female transmission rate due to
inflammation of the vagina;
it should not be considered a barrier to infection.
Research is clarifying the relationship between male
circumcision and HIV in differing social and cultural
contexts, however critics point out that any
correlation between circumcision and HIV is likely to
come from cultural factors (which govern not only
whether someone is circumcised, but also their
sexual practices and beliefs)
Even though male circumcision may lead to a
reduction of infection risk in heterosexual men by
up to 60%, UNAIDS believes that it is premature to
recommend male circumcision as part of HIV
prevention programs.
Trials, in which some uncircumcised men were randomly
assigned to be circumcised in presumably sterile
conditions and others were not circumcised, conducted in
Kenya and Uganda found that men who were
uncircumcised were twice as likely to contract the human
immunodeficiency virus (HIV) compared with circumcised
counterparts.
South African medical experts are concerned that the
repeated use of unsterilized blades in the ritual
circumcision of adolescent boys may be spreading HIV.
Kaposi's sarcoma in a 20-year old man who had AIDS.
New“ strategy under N. Ramjee, 2006
A, B, C, D, E, F, G, H, (I)
A – abstinence
B – be faithful – být si vzájemně věrný, buď věrný
C – kondom (mužský kondom)
C = také femidom neboli kondom
D – diafragma (poševní) with spermicid
D – dental dam – dentální rouška
E – exposure prophylaxis
F – female initiated microbicides
G – genital tract infections – therapy
H – HSV 2 suppression Herpes simplex 2
I – „imunity induced by vaccine“ ?????