AIDS

PRESENTED BY: DR.BISWAJEETA SAHA(1ST YR PG) MODERATOR: DR. N. SAHU, 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 moleculeactivation through T cell receptorby antigens

INFECTION OF NON T CELLS

HIV1 can infect and multiply in terminally differentiated macrophages They are reservoirs of infection

Macrophages

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
A.asymptomatic,acute HIV,persistent generalized lymphadenopathy B.Symptomatic ,not A or C C.AIDS indicator conditions

1 500cells/l
A1

2 200-499cells/l
A2

3 200cells/l
A3

B1

B2

B3

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

Kaposis 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 Kaposis 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 EIAAbs 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)

USEDiagnosis 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