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HIV and AIDS
HIV
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The human immunodeficiency virus (HIV) is
a lentivirus (a subgroup of retrovirus) that causes
the acquired immunodeficiency syndrome
(AIDS).
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AIDS is an infectious disease of the
immune system caused by human
immunodeficiency virus (HIV). AIDS is
characterized by a decrease in the number
of helper T cells, which causes a severe
immunodeficiency that leaves the body
susceptible to a variety of potentially fatal
infections.
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HIV infects vital cells in the human immune
system such as helper T cells (specifically CD4+
T cells), macrophages, and dendritic cells.
HIV is the causative agent of
AIDS
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Human immunodeficiency virus
retrovirus
most common type: HIV-1
HIV-1: distributed worldwide
HIV-2:mainly endemic in west Africa
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HIV: belongs to a group of viruses known:
known as as RETROVIRUSES (type of viruses
that carry their genetic material in the
form of ribonucleic acid[RNA] rather than
deoxyribonucleic acid [DNA].
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Human Immunodeficiency Virus is a lot like other viruses,
including those that cause the "flu" or the common cold. But
there is an important difference – over time, your immune
system can clear most viruses out of your body. That isn't the
case with HIV – the human immune system can't seem to get
rid of it.
HIV can hide for long periods of time in the cells of your body
and that it attacks a key part of your immune system – your Tcells or CD4 cells. Your body has to have these cells to fight
infections and disease, but HIV invades them, uses them to
make more copies of itself, and then destroys them.
Over time, HIV can destroy so many of your CD4 cells that
your body can't fight infections and diseases anymore. When
that happens, HIV infection can lead to AIDS.
When was it discovered?
 AIDS
was first recognized in June
5, 1981.
HIV and AIDS
an infectious agent – Kaposi’s Sarcoma
1981 - 26 cases of Kaposi’s sarcoma
• Young
• Male
• San Francisco and New York
• All Homosexuals
1981-1999: 46,684 definite cases in
United States
AIDS Definition
• AIDS is currently defined as the presence
of one of 25 conditions indicative of severe
immunosuppression
OR
• HIV infection in an individual with a CD4+ cell count
of <200 cells per cubic mm of blood
• AIDS is the end point of an infection that is continuous,
progressive and pathogenic
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The virus can be spread (transmitted):
Through sexual contact -- including oral,
vaginal, and anal sex
Through blood -- via blood transfusions or
needle sharing
From mother to child -- a pregnant woman can
transmit the virus to her fetus through their
shared blood circulation, or a nursing mother
can transmit it to her baby in her breast milk
Other methods of spreading the virus are rare
and include accidental needle injury, artificial
insemination with infected donated semen, and
organ transplantation with infected organs.
HIV entry into cells
Important HIV components
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Gp120 + CD4 RECEPTORS
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Viral reverse transcriptase : produces
complementary DNA using the viral RNA
template
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Provirus: Viral DNA is transported into the
nucleus and is integrated into the chromosome
Function of T cells
Macrophages:
The Trojan Horse
Macrophages form a reservoir outside
the blood
Carry virus into different organs (brain)
macrophages sustain HIV production for a long
time without being killed by virus
STAGE 1 : Primary HIV infection
This stage of infection lasts for a few weeks and is often accompanied by a
short flu-like illness.
 STAGE 2 : is stage lasts for an average of ten years and, it is free from major
symptoms, although there may be swollen glands. The level of HIV in the
peripheral blood drops to very low levels but people remain infectious and
HIV antibodies are detectable in the blood, so antibody tests will show a
positive result.
Research has shown that HIV is not dormant during this stage, but is very
active in the lymph nodes. A test is available to measure the small amount of
HIV that escapes the lymph nodes. This test which measures HIV RNA (HIV
genetic material) is referred to as the viral load test
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STAGE 3 : Symptomatic HIV infection
Over time the immune system becomes severely damaged by HIV. Initially
many of the symptoms are mild, but as the immune system deteriorates the
symptoms worsen.
Symptomatic HIV infection is mainly caused by the emergence of
certain opportunistic infections that the immune system would normally
prevent. This stage of HIV infection is often characterised by multi-system
disease and infections can occur in almost all body systems. Unless HIV itself
can be slowed down the symptoms of immune suppression will continue to
worsen.
 STAGE 4 : Progression from HIV to AIDS
 As the immune system becomes more and more damaged the individual may
develop increasingly severe opportunistic infections and cancers, leading
eventually to an AIDS diagnosis.
 In adults and children (aged 5 or over) the progression to AIDS is diagnosed
when any condition listed in clinical stage 4 is diagnosed and/or the CD4
count is less than 200 cells/mm3 . The criteria for diagnosing AIDS may
differ depending on individual country guidelines.
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Common with CD4 count below 200 cells/mm3:
Bacillary angiomatosis -- skin sores caused by a bacteria called Bartonella, which may be caused by
cat scratches
Candida esophagitis -- painful yeast infection of the esophagus
Pneumocystis jiroveci pneumonia "PCP pneumonia," previously called Pneumocystis carinii pneumonia,
caused by a fungus
Common with CD4 count below 100 cells/mm3:
AIDS dementia -- worsening and slowing of mental function, caused by HIV
Cryptococcal meningitis -- fungal infection of the lining of the brain
Cryptosporidium diarrhea -- extreme diarrhea caused by a parasite that affects the gastrointestinal
tract
Progressive multifocal leukoencephalopathy-- a disease of the brain caused by a virus (called the
JC virus) that results in a severe decline in mental and physical functions
Toxoplasma encephalitis -- infection of the brain by a parasite, called Toxoplasma gondii, which is
often found in cat feces; causes lesions (sores) in the brain
Wasting syndrome -- extreme weight loss and loss of appetite, caused by HIV itself
Common with CD4 count below 50/mm3:
Cytomegalovirus infection -- a viral infection that can affect almost any organ system, especially
the large bowel and the eyes
Mycobacterium avium -- a blood infection by a bacterium related to tuberculosis
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Typical Symptoms of AIDS tend to be:
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Weight reduction
Chills
Swollen lymph
Vitality loss
Diarrhoea
Persistent nausea
Coughing
Shortness of breath
Seizures
Painful swallowing
Lapse of memory
Continual headaches
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Today, according to the Centers for Disease
Control and Prevention, a person may also be
diagnosed with AIDS if they are HIV-positive and
have a CD4 cell count below 200 cells/mm3, even
if they don't have an opportunistic infection.
AIDS may also be diagnosed if a person develops
one of the opportunistic infections and cancers that
occur more commonly in people with HIV
infection. These infections are unusual in people
with a healthy immune system.
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the individual has had Pneumocystis carinii
pneumonia
OR
one of the above defining illnesses
AND
a CD4+ T-cell count <200 cells/µl or a
CD4+percentage <14%
TEST
Purpose
Serological tests:
ELISA
Initial Screening
Latex Agglutination
Initial Screening
Western Blot Analysis
Confirmation Test
Immunofluorescence
Confirmation Test
Other tests:
p24 antigen
Early Marker of Infection (detection of a recent
infection)
Virion RNA RT-PCR
Detection of virus in blood (detection of a recent
infection) and to confirm treatment efficacy.
CD4:CD8 T-cell Ratio
Staging the disease and to confirm treatment
efficacy.
Isolation and culture of virus
Only available in research labs.
P24 antigen (nucleocapid)
 produced
early in infection
 present in the patient's bloodstream
Reverse Transcriptase Polymerase Chain Reaction (RTPCR)
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for VIRAL LOAD
to detect HIV RNA in plasma
first 2-4 weeks of infection, when
patients may be seronegative and yet
are infective
Western blot: definitive diagnosis
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Antibody specific for HIV gp120 or gp160
(detectable within 4-8 weeks post-exposure)
However in 5% of the patients antibodies may
not be detectable for 6 months or more.
Western Blot
Band pattern
Interpretation
 Lane 1, HIV+ serum
(positive control)
 Lane 2, HIV- serum
(negative control)
 Lane A, Patient A
 Lane B, Patient B
 Lane C, Patient C
CD4+, CD8+ counts
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CD4+ is monitored every 3-6 months
-when to start PCP therapy
-monitor antiviral therapy
-when to start antiviral therapy
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Normal CD4+ levels:500 to 1600
Normal CD8+ levels: 375 to 1100
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Abnormal values
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CD percentage: refers to the total lymphocytes; more
reliable indicator of HIV; predictor of HIV disease
progression
CD4+
<200 = start PCP therapy
<100= toxoplasmosis; crytpcoccosis
<75= MAC
CD4+ percentage
>28%=normal
14-27%= intermediate
<14%= clinical AIDS
Abnormal values
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CD4/CD8 ratio
abNormal: 0.9 to 1.9
In HIV, CD8 appears increased due to decrease
of CD4
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There is no cure for AIDS at this time. However, a variety of treatments are available
that can help keep symptoms at bay and improve the quality and length of life for those
who have already developed symptoms.
Antiretroviral therapy suppresses the replication of the HIV virus in the body. A
combination of several antiretroviral drugs, called highly active antiretroviral therapy
(HAART), has been very effective in reducing the number of HIV particles in the
bloodstream. Preventing the virus from replicating can improve T-cell counts and help
the immune system recover from the HIV infection.
HAART is not a cure for HIV, People on HAART with suppressed levels of HIV can
still transmit the virus to others. There is good evidence that if the levels of HIV remain
suppressed and the CD4 count remains high (above 200 cells/mm3).
However, HIV may become resistant to one combination of HAART, especially in
patients who do not take their medications on schedule every day. Genetic tests are
now available to determine whether an HIV strain is resistant to a particular drug. This
information may be useful in determining the best drug combination for each person,
and adjusting the drug regimen if it starts to fail.
When HIV becomes resistant to HAART, other drug combinations must be used to try
to suppress the resistant strain of HIV.
HAART (Highly Active Antiretroviral
Therapy)
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available since 1995
results in suppression of viral replication
halts damage to the immune system
partially restores the immune system leading to
partial restoration of immune function
fewer opportunistic infections and longer life for
the patients.
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DrugsAzidothymidine (AZT, zidovudine, Retrovir)
prolongs survival but does not eliminate the virus,
Inhibits proviral DNA synthesis but does not
eliminate the virus.
Dideoxyinosine(ddI, didanosine, videx) mechanism
of action is similar to AZT
A promising vaccine for the most common serious
infection(PCP) in people with HIV could reach
clinical trials next year: 2013.
When to start treatment
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history of an AIDS-defining illness or with a
CD4 T-cell count <350 cells/mm3.
Antiretroviral therapy should also be
initiated in the following groups of patients
regardless of CD4 T-cell count:
a. Pregnant women
b. Patients with HIV-associated
nephropathy
c. Patients coinfected with HBV
PREVENTION
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The male latex condom is the single most effective
available technology to reduce the sexual transmission
of HIV and other sexually transmitted infections.
oil-based lubricants such as petroleum jelly, butter, and
lard not be used with latex condoms
dissolve the latex, make the condoms porous
water-based lubricants