AIDS

ACQUIRED
IMMUNODEFICIENCY
SYNDROME (AIDS)
AIDS is a disease caused by the retrovirus
human immunodeficiency virus (HIV) and
characterized by profound
immunosuppression that leads to
opportunistic infections, secondary
neoplasms, and neurologic manifestations.
ROUTE OF TRANSMISSION
1. Sexual transmission:
 M/C mode of transmission
 75% of cases
 Homosexual /bisexual male
 Heterosexual sex
 Male to male, male to female and female
to male transmission.
2.Parenteral transmission / transmission via
blood and blood products.
 Seen in 20-25% of cases
 Seen in 3 conditions.
1. Intravenous drug abusers,
2. Hemophiliacs who received factor VIII
and factor IX concentrates, and

3. Random recipients of blood transfusion.
3. Perinatal transmission / mother-to-infant
transmission / vertical transmission
 Infected mothers can transmit the infection to
their offspring by three routes
1. In utero by transplacental spread
2.During delivery through an infected birth
canal, and
3. After birth by ingestion of breast milk.
 Transmission during birth (intrapartum) and in
the immediate period thereafter (peripartum) is
considered to be the most common mode.
4. Occupational transmission:
 Seen in health care workers, lab workers
and those engaged in disposal of waste
sharps.
 Universal precaution: Disinfecting and
sterilizing all reusable devices and use of
bleaching solution for disinfecting all
blood spillages.
 Seroconversion has been documented after
accidental needle-stick injury or exposure of non-
intact skin to infected blood in laboratory
accidents.
 After needle-stick accidents, the risk of
seroconversion is believed to be about 0.3%.
 Antiretroviral therapy given within 24 to 48
hours of a needle stick can reduce the risk of
infection eightfold.
 By comparison, approximately 30% of those
accidentally exposed to hepatitis B–infected blood
become seropositive.
5. Transmission by other body fluids:
 Saliva, tears, sweat, urine.
 Semen, vaginal secretions, cervical
secretions.
 Breast milk, CSF etc.
HIV INFECTION CANNOT BE
TRANSMITTED BY
 Casual personal contact in the household,

workplace, or school.
 Shaking hands, hugging, sharing house
hold facilities like beds, toilets, utensils
etc.
HIV contaminated waste products can be
sterilized and disinfected
 Sodium hypochlorite
 5% formaldehyde
 70% ethanol
 2% glutaraldehyde
 β- propionolactone
 HIV is heat sensitive and can be inactivated
at 56̊ C for 30 minutes.
ETIOLOGY OF HIV
 HIV, a non transforming human retrovirus

belonging to the Lentivirus family.
 Two genetically different but related forms
of HIV isolated from AIDS patients.
1. HIV-1: United States, Europe, and
Central Africa,
2. HIV-2: West Africa and India.
STRUCTURE OF HIV
 HIV-1 virion is spherical and contains an
electron-dense, cone-shaped core
surrounded by a lipid envelope derived from
the host cell membrane.
 The virus core contains
(1) The major capsid protein p24;

(2) Nucleocapsid protein p7/p9;
(3) Two copies of genomic RNA; and
(4) The three viral enzymes (protease,
reverse transcriptase, and integrase).
 The viral core is surrounded by a matrix
protein called p17 which lies underneath the
virion envelope.
 Studding the viral envelope are two viral
glycoproteins, gp120 and gp41, which are
critical for HIV infection of cells.
 HIV-1 RNA genome contains 3 important
genes
1. gag (group antigen) for core protein.
2.pol (polymerase) for reverse
transcriptase
3. env (envelope) for envelop proteins.
 other accessory genes
 tat, rev, vif, nef,vpr, and vpu

 tat (transactivator) gene causes a 1000-fold
increase in the transcription of viral genes
and is therefore critical for virus replication
PATHOGENESIS OF HIV INFECTION AND AIDS
 While HIV can infect many tissues, there are two
major targets of HIV infection: the immune
system and the central nervous system.
 Hallmark of AIDS: Profound immune deficiency,
primarily affecting cell-mediated immunity.
 Largely related to depletion of CD4+ T cells
(helper T cells) resulting in profound
immunosuppression.
 Macrophages and dendritic cells are also targets of
HIV infection.
 HIV enters the body through mucosal
tissues and blood
 First infects T cells as well as dendritic
cells and macrophages.
 The infection becomes established in
lymphoid tissues, where the virus may
remain latent for long periods.
 Active viral replication is associated with
more infection of cells and progression to
AIDS.
LIFE CYCLE OF HIV
 Life cycle of HIV consists of

1. Infection of cells
2. Integration of the provirus into the host cell
genome
3. Activation of viral replication, and
4. Production and release of infectious virus
HIV INFECTION OF NON-T CELLS
 Circulating monocytes, tissue macrophages
and dendritic follicular cells of lymph
nodes are also infected.
 HIV infected monocytes and macrophages
do not get destroyed but become a
reservoir of HIV infection.
 Infected dendritic follicular cells of the
lymph nodes causes massive enlargement of
lymph nodes.
HIV INFECTION OF NERVOUS SYSTEM
 Infected CD4+ monocytes-macrophages carry

infection to microglia.
 Direct infection of astrocytes and
oligodendrocytes.
 Neurons are not invaded by HIV but are
affected due to attachment of gp120 and by
release of cytokines by HIV-infected
macrophages.
MAJOR ABNORMALITIES OF IMMUNE
FUNCTION IN AIDS
T cell abnormalities:
 Lymphopenia
 CD4+ T cell depletion
 CD8+ T cell lymphocytosis
 Reversal of CD4:CD8 cell ratio
 Decreased production of cytokines by
CD4+ T cells.
 Decreased ADCC by CD8+ T cells.
B cell abnormalities:
 No direct viral damage
 Decrease Ig production
 Polyclonal activation
 Hypergammaglobulinemia
 Circulating immune complexes

 NKcell abnormalities
 No direct viral damage
 Decreased number
 Decreased cytotoxicity
 Monocyte-Macrophage cell abnormalities

 No destruction
 Decreased chemotaxis
 Decreased cytotoxicity
 Decreased class II HLA expression.
NATURAL HISTORY OF HIV INFECTION
 HIV disease begins with acute infection,
which is only partly controlled by the
adaptive immune response, and advances to
chronic progressive infection of peripheral
lymphoid tissues.
 3 phases of clinical manifestions.
1. Acute HIV/ retroviral Syndrome

2. Middle, chronic phase
3. Clinical AIDS/ final crisis phase
Acute HIV/ retroviral Syndrome (3-12 weeks)
 Entry of HIV in body leads to
 High level of plasma viremia
 Formation of anti HIV antibody after 3-6 weeks of

initial exposure.
 Initially, sudden marked reduction in CD4+ T cells
followed by return to normal level.
 Rise in CD8+ T cells.
 Appearance of self limited non specific flu like acute

viral illness:
 sore throat, fever, myalgia, skin rash and rarely
aseptic meningitis.
 Resolve spontaneously in 2-3 weeks.
MIDDLE, CHRONIC PHASE (10-12 YEARS)
 Viremia due to viral replication continues.
 Moderate fall in CD4+ T cell count
 Cytotoxic CD8+ T cell count remains high
 Clinically this stage is a stage of latency
 Patient may be asymptomatic or may

develop mild constitutional symptoms
and persistent generalised
lymphadenopathy.
Clinical AIDS/ final crisis phase
 Characterized by profound
immunosuppression and onset of full- blown
AIDS.
 Marked increase in viremia
 CD4+ T cell count is markedly reduced
(<200 cells/µl)
REVISED CDC HIV/AIDS CLASSIFICATION
Phase Early, acute Middle, Final, crisis

chronic
Period after 3-6 weeks 10-12 years Any period

infection upto death
CDC A B C
clinical
category
CDC CD+ T ≥ 500/µl 200-499/µl <200/µl
cell count
Category A : include
 Asymptomatic cases
 Persistent generalized lymphadenopathy
(PGL)
 Acute HIV syndrome
Category B : include
 Symptomatic cases
 Condition secondary to CMI
 Bacillary dysentry
 Mucosal candidiasis
 Fever
 Oral hairy leukoplakia
 ITP
 PID
 Peripheral neuropathy
 Cervical dysplasia
 CIS cervix
Category C : include
 AIDS surveillance case definition
 Mucosal candidiasis
 Cancer uterine cervix
 Bacterial infection (TB)
 Fungal infections (histoplasmosis)
 Parasitic infections (pneumocystis carinii
pneumonia)
 Malnutriton
 Wasting of muscles
PATHOLOGICAL LESION AND CLINICAL
MANIFEATION OF AIDS
TESTS FOR DIAGNOSIS OF AIDS

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ACQUIRED

2. Hemophiliacs who received factor VIII

and factor IX concentrates, and

 Casual personal contact in the household,

 HIV, a non transforming human retrovirus

(1) The major capsid protein p24;

 tat, rev, vif, nef,vpr, and vpu

 Life cycle of HIV consists of

 Infected CD4+ monocytes-macrophages carry

 No direct viral damage

 Circulating immune complexes

 Monocyte-Macrophage cell abnormalities

1. Acute HIV/ retroviral Syndrome

 Formation of anti HIV antibody after 3-6 weeks of

 Appearance of self limited non specific flu like acute

 Patient may be asymptomatic or may

Phase Early, acute Middle, Final, crisis

Period after 3-6 weeks 10-12 years Any period

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