A LECTURE ON AIDS FOR FIRST MBBS STUDENTS, DEPT OF BIOCHEMISTRY. A CLASS ON EPIDEMIOLOGY, VIROLOGY,HIV-MORPHOLOGY, GENOME, LIFE CYCLE,MODE OF TRANSMISSION, IMMUNOLOGY, PATHOPHYSIOLOGY AND PATHOGENESIS, LABORATORY DIAGNOSIS AND MANAGEMENT.

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

2. 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).

3. 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

4. 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.

5. 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

6. Protease ( p10)
Integrase (p32)
P17
Membrane
Antigen

7. 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

8. 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

9. 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.

10. 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.
gag
pol
vif vpu env
vpr
nef
tat
rev
U3 R U5

11. 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.

12. 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.

13. 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.

16. Modes of Transmission
• Sexual transmission
• Transmission by blood & blood products
• Maternal – fetal / infant transmission
• Occupational transmission : Health care workers,
Laboratory workers etc

17. 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

19. 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

20. 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

21. 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

22. 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

29. • The disease is characterized by,
1.Immuno suppression.
2.Secondary neoplasm
3.Neurological manifestations.
4.Opportunistic infections

30. 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

31. 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

32. Management of AIDS
ANTIRETROVIRAL 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)

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

34. 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.

35. • 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.

36. Thank You !