AIDSPRESENTED BY: DR.BISWAJEETA SAHA(PG)

DEPT OF PATHOLOGY,KIMS,BBSR

INTRODUCTION 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

Sexual route

IV drug use

Mother to baby

Body fluids

HUMAN IMMUNODEFICIENCY VIRUS Icosehadral(20 sided)

enveloped 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)

PATHOGENESIS

Two major targets of HIV-immune system and central nervous system

Profound cell mediated immunodeficiency is the hallmark

Mainly affects CD4+Tcells,dendritic cells and macrophages.

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 with infection

In addition to direct killing of CD4+T cells,other mechanisms are:

HIV cause progressive architectural and cellular destruction of lymph nodes

Chronic activation of uninfected cells leads to activation induced cell death

Loss of precursors of CD4+ T cells Fusion of infected and uninfected cells-leads to

balloning and cell death 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

Macrophages HIV1 can infect and multiply in terminally differentiated

macrophages They are reservoirs of infection

Dendritic cells Mucosal dendritic cells transport to regional lymph nodes Follicular ones are potent reservoir

B cells Polyclonal activation ---germinal centre B cell hyperplasia, BM

plasmacytosis, hypergammaglobulinimia, formation of circulating immune complexes

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

T CE

CDC CLASSIFICATION CATEGORIES OF HIV

Clinical categories

1≥500cells/μl

2200-499cells/μl

3≤200cells/μl

A.asymptomatic,acute HIV,persistent generalized lymphadenopathy

A1 A2 A3

B.Symptomatic ,not A or C

B1 B2 B3

C.AIDS indicator conditions

AIDS DEFINING OPPORTUNISTIC INFECTION AND NEOPLASMS Protozoal and helminthic infection Cryptosporidiosis Toxoplasmosis

Fungal infection Pneumocystosis Candidiasis Cryptococcosis Coccidioidomycosis Histoplasmosis

Bacterial infections Mycobacteriosis Nocardiosis

Viral infections Cytomegalovirus HSV Varicella zoster Progressive multifocal leukoencephalopathy

NEOPLASMS

Kaposi’s sarcoma

Non-hodgkin B cell lymphoma

Cervical cancer in women

Anal cancer in men

25-40% of HIV patients develop malignancy

ORAL CANDIDIASIS

KAPOSI SARCOMA

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 HIV infection

Cryptococcal meningitis

Pulmonary/extrapulmonary TB

Kaposi’s sarcoma

Neurological impairment

Candidiasis of esophagus

Clinically diagnosed life threatening or recurrent episodes of

pneumonia with or without etiological confirmation

Invasive cervical cancer

LABORATORY INVESTIGATIONS

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

HIV POSITIVITY

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 detectable levels.

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:

Antibody

Antigen

Viral nucleic acid

Virus in culture

ELISA 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 Sensitivity->99.5% 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 Auto antibodies Hepatic disease Recent influenza Acute viral infections

So EIA confirmed by western blot, p24 Ag capture assay or HIV RNA tests.

WESTERN BLOT

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

following antigens

must be present:

p24, p31, gp41 or

gp120/160.

CDC criteria require 2

bands of the following:

p24, gp41 or

gp120/160

INDIRECT IMMUNOFLOURESCENCE

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 antibody.

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 appears.

Greatest use as a screening test for persons suspected to

have acute HIV syndrome.

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

newborns

CSF

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—

RT-PCR

Branched DNA

Nucleic acid sequence based amplification (NASBA)

USE-

Diagnosis

Initial prognosis

Determining need for therapy

Monitoring effects of therapy

VIRUS ISOLATION

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 releasing virus.

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 blood.

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 blood.

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 more promising.

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 birth)

HIV DNA PCR- diagnostic at 1 mth of age

TREATMENT

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 Protease inhibitors Fusion inhibitors

Major causes of morbidity are-cancer,accelerated

cardiovascular diseases,kidney diseases and liver diseases.

PREVENTION

Monogamous Relationship

Protected Sex

Sterile needles

Proper screening of blood products before

transfusion

THANK YOU