a lecture on aids for mbbs 2014

For I MBBS By Liji Nair, Assistant Professor, Department of Biochemistry

AIDS (Acquired Immuno Deficiency

Syndrome)Introduction:

• AIDS is a retroviral disease caused by human

Immuno deficiency virus (HIV)

• AIDS is invariably fatal since there is no cure.

• Based on clinical manifestation, the disease was

named as acquired Immuno deficiency

syndrome (AIDS).

Epidemiology

• AIDS is a global disease with an alarming increase

in the incidence of occurrence

• It is assumed that the virus entered in India in 1980

• India has the second largest number of HIV

infected people

The sooty mangabey source of HIV-2 and the chimpanzee source of HIV-1

Virology of HIV

• AIDS is caused by a retro virus, HIV.

• HIV is a single stranded RNA VIRUS

• They replicate with the help of the reverse

transcriptase (RT) or RNA dependent DNA

polymerase.

Morphology of HIV(Structure of the virus)

• The virus is spherical with a diameter of about 110 nm

• It contain a core, surrounded by a lipid envelop

derived from host plasma membrane.

• The core of the HIV has two strands of genomic

RNA.

• The protein components are named after its

molecular weight

Protease ( p10)

Integrase (p32)

P17Membrane

Antigen

Major Core proteins

• Reverse transcriptase (RT) : p66 and p55

• Endonuclease : p32

• Proteases : p10

• Nucleocpsid protein (p9)

• The viral core is surrounded by the major

capsid Ag : p24

• The outer shell is composed of the membrane

Ag, P17

Surface Antigens

• The lipid membrane of the virus is studded

with two glycoprotein, gp120 and gp41

• gp120 , surface Ag is important for the viral

infection and the detection of AIDS

Reverse transcriptase • The hallmark of a retrovirus.

• Following the entry into the host cells, the genetic

information from the RNA of HIV is transcribed

into DNA by the viral Reverse transcriptase (RT)

• Viral RT is a RNA dependent DNA polymerase

• Here RNA acts as a template

• HIV has an extra ordinary rate of replication.

HIV Genome

5’ 3’LTR LTR

gag – core proteins (including p24)

pol – envelope glycoproteins

env – enzymes (RT, protease, Integrase)

tat, rev, nef, vif, vpu, vpr – proteins in the modification of host cell

to enhance virus growth and regulate viral gene

expression

LTR – Long Terminal Repeats- for initiation of transcription.

gagpol

vif vpu env

vpr

nef

tat

revU3 R U5

HIV LIFE CYCLE :

HIV entry, replication and release

1. HIV binds to cell surface via receptors (CD4

molecules and co receptors) CD4 molecules

are present on the surface of T-helper cells.

Macrophages, monocytes, Langerhans cells

& glial cells are also susceptible.

2. Viral uncoating in cytoplasm.

3. Viral genome trancribed to DNA copy by

reverse trancriptase.

4. DNA copy integrates into host cell DNA by

integrase.

5. Following cell activation viral genes are

transcribed & translated by the host cell

mechanism.

6. HIV proteases cleaves the functional viral

proteins from polypeptides (protease inhibitor

drugs acts here).

7. Virion assembly takes place.

8. Viral release from the cell surface by budding

and Cell lysis.

Modes of Transmission

• Sexual transmission

• Transmission by blood & blood products

• Maternal – fetal / infant transmission

• Occupational transmission : Health care workers,

Laboratory workers etc

Immunology

• CD4 (T-helper) lymphocytes are decreased in

number immunodeficiency

• Macrophages & monocytes act as the reservoir of

HIV infection, which disseminate the virus to various

organs

• Reduced T-killer cytotoxic activity

• Poor antibody response and lowered lymphokines

Natural course of the disease

Three distinct phases are identified

1. Acute phase (Window period): is the initial

body response to HIV infection.

• It is characterized by high rate of virus

production, which are lodged in the lymphoid

tissue, but it cannot be detected easily

• This phase lasts for 8 – 12 months

2) Chronic phase

• During this period body tries to contain the virus.

• Person may appears normal (immune system is

intact)

• Is a carrier state & can transmit the disease

• Antibodies to HIV are found in the blood (hence

this phase is also referred as seropositive period)

• Lasts for 5 – 10 years

3) Crisis state ( AIDS disease)

• Clinical manifestations appear

• Plasma level of virus is tremendously increased

• Immune suppression occurs

• Is characterized by opportunistic infections

• Patients usually die within about 2 years

Pathophysiology & Pathogenesis

• Primary HIV Infection – Initial viremia &

dissemination of virus – also experience acute

HIV related syndrome.

• Establishment of chronic and persistent infection

• Advanced HIV disease

• The disease is characterized by,

1.Immuno suppression.

2.Secondary neoplasm

3.Neurological manifestations.

4.Opportunistic infections

Laboratory diagnosis of AIDS

1. The detection of Antibodies in the circulation by

ELISA

But there is a slight chance for false positive result

2. Western blot analysis : Is a more specific test for HIV

antibodies.

Antibodies against six different components of the

virus are analyzed.

Western blot analysis employed for confirmation

of ELISA positive patients

3. T–Helper count is lowered. (normal level is

>400/cmm)

In AIDS the level is always <300 cmm

4. PCR can be used to detect the presence of HIV

genes in the peripheral blood lymphocytes

The number of HIV particle in the blood is

estimated

Management of AIDSANTIRETROVIRAL THERAPY

• RT inhibitors

- Nucleoside analogues (NRTIs):

Eg: AZT (Zidovudine), Abacavir, Stavudine,

Lamivudine, Zalcitabine etc

- Non nucleoside analogues(NNRTIs)

Eg: Loviridine, Nevirapine, Delavirdine etc

• Protease Inhibitors

Indinavir, Ritonavir, Nelfinavir etc

Combination of drugs – HAART

(Highly Active Anti Retroviral

Therapy)

Prevention

• Public education and awareness - to limit the spread of HIV infection

To limit the spread……….

• Avoidance of extra marital relationships.

• Blood samples should be tested before

transfusion.

• Syringes and needles should be properly

sterilized.

• Disposable syringes and needles are to be used

and destroyed immediately after use.

• Boiling for 10 minutes – inactivate the virus

• Ordinary autoclaving at 120ºC for 20 minutes –

effective to sterilize instruments and gloves.

• Heat sensitive instruments must be

decontaminated by immersing in 2%

glutaraldehyde.

• Blood spills by washing with 1% sodium

hypochlorite solution with 10,000 ppm chlorine.

Thank You !