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HIV and AIDS
PM2 PATHOPHYSIOLOGY
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
When was it discovered?
 AIDS
5,1981
was first recognized in June
HIV and AIDS
Pneumocystis pneumonia
107 cases of Pneumocystis carinii pneumonia
United States, pre-AIDS epidemic
AIDS epidemic has resulted in 166,368 cases up to 1999
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
HIV and AIDS
Two rare diseases in the gay community linked
to
IMMUNOSUPPRESSION
OPPORTUNISTIC INFECTIONS
Lymphadenopathy
cases
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diffuse, undifferentiated non-Hodgkins lymphoma
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1977- 1980: No cases in the young male (20 - 39
years old) population of the San Francisco area
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March 1981 - January 1982: four cases within 10
months
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Gay-Related Immune Deficiency
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Acquired Immune Deficiency Syndrome
(AIDS)
HIV and AIDS
Distinguishing characteristics
• Clusters of infected men
• Apparent concentration within sexually interactive
groups
• High numbers of sex partners
Suggests an infectious agent
HIV and AIDS
More evidence for an infectious agent
Different ways of getting a similar syndrome
• Blood transfusions
• Intravenous drug use
• Hemophilia (clotting factor)
Female sex partners of AIDS-positive IV drug users and
hemophiliacs
Haitian origin
HIV and AIDS
1983: The 4H Club
• Homosexuality among males
• Hemophilia
• Heroin use
• Haitian origin
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
AIDS Statistics
• Approximately 40,000,000 people in the world
are HIV-infected
•14,000 new HIV infections occur daily around
the world
-Over 90% of these are in developing
countries
-1000 are in children less than 15 years
of age
-Of adult infections, 48% are in women
Modes of transmission
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most common means in the world:
sexual contact
blood or blood product transfusion (before routine
testing)
transplanted tissue (before routine testing)
IV drug use with shared needles
transplacental (in utero) or by perinatal infection of
neonates (breast milk)
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
Population Polymorphism
EVERY new virus has at least one mutation!
The HIV that infects a patient is very different from that seen
by the time AIDS appears
4 stages of HIV infection
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Stage I: asymptomatic
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Stage II:
minor mucocutaneous manifestations
recurrent upper respiratory tract
infections
4 stages of HIV infection
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Stage III:
unexplained chronic diarrhea>1 month
severe bacterial infections
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Stage IV:
toxoplasmosis of the brain
candidiasis of the esophagus, trachea,
bronchi or lungs
Kaposi's sarcoma
AIDS-defining diseases
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Candidiasis of bronchi, trachea, or lungs
Candidiasis esophageal
Cervical cancer (invasive)
Coccidioidomycosis, disseminated or
extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal for longer
than 1 month
Cytomegalovirus disease (other than liver, spleen
or lymph nodes)
AIDS-defining diseases
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Encephalopathy (HIV-related)
Herpes simplex: chronic ulcer(s) (for more than 1
month); or bronchitis, pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (for more than 1
month)
Kaposi's sarcoma
Lymphoma Burkitt's, immunoblastic or primary
brain
Mycobacterium avium complex
AIDS-defining diseases
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Mycobacterium, other species, disseminated or
extrapulmonary
Pneumocystis carinii pneumonia
Pneumonia (recurrent)
Progressive multifocal leukoencephalopathy
Salmonella septicemia (recurrent)
Toxoplasmosis of the brain
Tuberculosis
Wasting syndrome due to HIV
However, when an individual shows negative lab results for HIV
infection, the diagnosis of AIDS is still considered if:
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1) the patient has not undergone high-dose corticoid
therapy,other immunosuppressive/cytotoxic therapy in the
three months before the onset of the indicator disease
OR
2) the patient has not been diagnosed with Hodgkin's
disease, non-Hodgkin's lymphoma, lymphocytic leukemia,
multiple myeloma, or any cancer of lymphoreticular or
histiocytic tissue, or angioimmunoblastic
lymphoadenopathy
OR
3)the patient does not have a genetic immunodeficiency
syndrome atypical of HIV infection, such as one involving
hypogamma globulinemia
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AND
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.
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
Normal: 0.9 to 1.9
In HIV, CD8 appears increased due to decrease
of CD4
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1. Nonnucleoside Reverse Transcriptase Inhibitors
(NNRTIs)
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2. Nucleoside Reverse Transcriptase Inhibitors
(NRTIs),
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3. Protease Inhibitors (PIs)
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4. Fusion Inhibitors
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1. Nonnucleoside Reverse Transcriptase Inhibitors
(NNRTIs)
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2. Nucleoside Reverse Transcriptase Inhibitors
(NRTIs),
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3. Protease Inhibitors (PIs)
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4. Fusion Inhibitors
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.
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