First indication came in 1981 from New York and LA,of a sudden outbreak
of two very rare diseases, Kaposi sarcoma and Pneumocystis carini
pneumonia in young adults who were homosexuals or addicted to injected
narcotics. This condition was named AIDS.
Discovered independently by Luc Montagnier of France and Robert Gallo
of the US in 1983-84
AIDS in India was 1st detected in commercial sex workers in
Tamil Nadu in 1986& has been growing very fast since then.
Causative agent- Human Immunodeficiency Virus(HIV), lentivirus
subgroup of family retroviridae.
AIDS is a global pandemic
2007-33.2 million individuals living with AIDS
ROUTES OF TRANSMISSION
IV drug use
Mother to baby
HUMAN IMMUNODEFICIENCY VIRUS
90-120 nm in size
Outer icosehedral shell and a
inner core enclosing RNAs
2 genetically different but related forms of HIV-HIV1
and HIV 2
HIV 2 more common in India
On basis of genetic analysis,HIV 1 can be subdivided
into 3 subgroups-M(major).O(outlier),N(neither)
Group M most common worldwide
M further divided into subtypes A to K.
Clade C is the fastest spreading worldwide.
THE HIV GENOME
Structural genes-gag, pol, env
Nonstructural genes and regulatory genes tat (transactivating gene)
nef (negative effector gene)
rev (regulator of virus gene)
vif (viral infectivity factor gene)
vpu (viral protein U)
vpr (viral protein R)
LTR (long terminal repeat)
Two major targets of HIV-immune system and central
Profound cell mediated immunodeficiency is the
Mainly affects CD4+Tcells,dendritic cells and
Enters body through mucosal tissues and blood--infects T cells,dendritic cells and macrophages--infection establishes in lymphoid organs---virus
remains latent ----active viral replication associated
In addition to direct killing of CD4+T cells,other mechanisms are:
HIV cause progressive architectural and cellular destruction of
Chronic activation of uninfected cells leads to activation induced
Loss of precursors of CD4+ T cells
Fusion of infected and uninfected cells-leads to balloning and cell
Apoptosis of uninfected CD4+T cells by binding of soluble gp120 to
CD4 molecule—activation through T cell receptorby antigens
INFECTION OF NON T CELLS
HIV1 can infect and multiply in terminally differentiated macrophages
They are reservoirs of infection
Mucosal dendritic cells transport to regional lymph nodes
Follicular ones are potent reservoir
Polyclonal activation ---germinal centre B cell hyperplasia, BM
plasmacytosis, hypergammaglobulinimia, formation of circulating immune
MAJOR ABNORMALITIES OF IMMUNE SYSTEM
Decreased T cell function:
Preferential loss of activated and memory T cells
Decreased delayed type hypersensitivity
Susceptibility to opportunistic infection
Susceptibility to neoplasm
Polyclonal B cell activation :
Hypergammaglobulinimia,circulating immune complexes
Inability to mount immune response to new antigens
Altered monocyte/macrophage function:
Decreased chemotaxis and phagocytosis
Decrease class II MHC expression
Diminished capacity to present antigen to T cells
NATURAL HISTORY OF HIV INFECTION
CDC CLASSIFICATION CATEGORIES OF HIV
B.Symptomatic ,not A
Non-hodgkin B cell lymphoma
Cervical cancer in women
Anal cancer in men
25-40% of HIV patients develop malignancy
EXPANDED WHO CASE DEFINITION FOR AIDS
An adult or adolescent(>12yrs) is considered to have AIDS if a test for HIV Ab
gives +ve result,and one or more of the following conditions are present
≥10% body wt loss or cachexia with diarrhoea or fever or both,intermittent or
constant,for atleast 1 month,not known to be due to a condition unrelated to
Candidiasis of esophagus
Clinically diagnosed life threatening or recurrent episodes of pneumonia with
or without etiological confirmation
Invasive cervical cancer
Hematological investigations- anaemia of chronic
disease,neutropenia,lymphopenia(CD4+Tcell),thromb ocytopenia.Raised ESR.
p/s: atypical lymphocytes having a plasmacytoid appearance.
CD4+:CD8+T cells- ratio is reversed
Hypergammaglobulinemia : IgG & IgA levels raised
Lymph node biopsy -follicular hyperplasia
CSF- lymphocytic pleocytosis
The presence of antibodies against HIV in human body is termed
HIV positivity & the person is called HIV positive
It takes 6-12 weeks after infection for antibodies to rise to
So,there is a window period during which infected person may
transmit the infection despite being seronegative.
During this window period p24 antigen capture assays are useful
LABORATORY DIAGNOSIS OF HIV INFECTION
Methods utilized to detect:
Viral nucleic acid
Virus in culture
Antibodies detected in ELISA include those directed against: p24, gp120,
gp160 and gp41, detected first in infection and appear in most individuals
Standard blood screening test
4th generation EIA test combine detection of Abs to HIV with detection of
p24 Ag for HIV
False positive EIA-
Abs to class II Ag
Acute viral infections
So EIA confirmed by western blot, p24 Ag capture assay or HIV RNA tests.
Most popular confirmatory test
The following antigens must be present: p17, p24, p31, gp41,
p51, p55, p66, gp120 and gp160.
Antibodies to gp31, gp41, gp 120, and gp160 appear later but are
present throughout all stages of the disease.
Advantage-multiple antigens elicit production of specific
antibodies and can be detected as discrete bands on western blot
Interpretation of results.
No bands, negative.
In order to be
interpreted as positive a
minimum of 3 bands
directed against the
must be present: p24,
p31, gp41 or
CDC criteria require 2
bands of the following: p24,
gp41 or gp120/160
Can be used to detect both virus and antibody to it.
Antibody detected by testing patient serum against antigen applied
to a slide, incubated, washed and a fluorescent antibody added.
Virus is detected by fixing patient cells to slide, incubating with
P24 ANTIGEN CAPTURE ASSAY
The p24-antigen screening assay is an EIA performed on serum or plasma.
P24 antigen only present for short time, disappears when antibody to p24
Greatest use as a screening test for persons suspected to have acute HIV
Test not recommended for routine screening as appearance and rate of
rise are unpredictable.
Sensitivity lower than ELISA.
Most useful for the following:
early infection suspected in seronegative patient
monitoring disease progress
CD4+ T CELL COUNT
Most widely used predictor of HIV progression.
Risk of progression to an AIDS opportunistic infection or
malignancy is high with CD4+T cell<200 cells/mcl
Percentage may be more reliable than CD4 count
Risk of progression to an AIDS opportunistic infection or
malignancy is high with percentage <20% in absence of treatment
Routine blood donor screening is done by nucleic acid testing.
3 assays are used where measurement of anti HIV Ab may be misleading—
Nucleic acid sequence based amplification (NASBA)
Determining need for therapy
Monitoring effects of therapy
Virus isolation can be used to definitively diagnose HIV.
Best sample is peripheral blood, but can use CSF, saliva, cervical
secretions, semen, tears or material from organ biopsy.
Cell growth in culture is stimulated, amplifies number of cells
Cultures incubated one month, infection confirmed by detecting
reverse transcriptase or p24 antigen in supernatant
VIRAL LOAD TEST
Viral load or viral burden is the quantity of HIV-RNA that is in the
RNA is the genetic material of HIV that contains information to
make more virus.
Viral load tests measure the amount of HIV-RNA in one milliliter of
Take 2 measurements 2-3 weeks apart to determine baseline.
Repeat every 3-6 months in conjunction with CD4 counts to
monitor viral load and T-cell count.
Repeat 4-6 weeks after starting or changing antiretroviral therapy
to determine effect on viral load.
TESTING OF NEONATES
Difficult due to presence of maternal IgG antibodies.
Use tests to detect IgM or IgA antibodies, IgM lacks sensitivity, IgA
Measurement of p24 antigen.
PCR testing may be helpful but still not detecting antigen soon
enough: 38 days to 6 months to be positive
TESTING IN PREGNANT MOTHER
Screening to be done in 1st trimester of pregnancy
Maternal IgG crosses placenta & persists in infant blood for 15
mths.so standard EIA HIV serologic tests cannot be used to diagnose
infection in infant
IgM & IgA in infants are assayed (but not reliable in 1st 3 mths after
HIV DNA PCR- diagnostic at 1 mth of age
Antiretroviral drugs target-protease,integrase,reverse transcriptase.
Highly active anti retroviral therapy( HAART )
Four approved classes of drugs in the HAART regimens
Nucleoside and nucleotide reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Major causes of morbidity are-cancer,accelerated cardiovascular
diseases,kidney diseases and liver diseases.
Proper screening of blood products before transfusion