The document provides an overview of HIV and AIDS, including: - The origin and history of HIV, tracing it back to transfers from chimpanzees to humans in Africa in the late 19th/early 20th century. - The structure and life cycle of HIV, which involves adsorption, penetration, reverse transcription, integration, transcription, and assembly/release of new virus particles. - How HIV interacts with and affects the immune system, preferentially infecting CD4+ T cells and macrophages/monocytes and ultimately causing immunosuppression. - The four stages of HIV infection: primary infection, asymptomatic stage, symptomatic stage, and AIDS.

1. HIV & AIDS
Presented By:

2. CONTENTS
 Introduction of HIV  HIV vaccines
 History & origin  Microbicides
 Crossgenesis & systematic  Agents And Factors
position Responsible For Causing
 Structure AIDS other than HIV
 Antigenic variation &  Some myths about AIDS
diversity  Current researches on
 HIV genome AIDS
 Life cycle
 Working of immune system
 Pathogenesis & stages of
HIV infection
 Clinical features
 Epidemiology &
transmission
 Diagnosis

3. HIV
Human Immunodeficiency Virus
Similar to SV40 & HTLV
An HIV particle is around 100-150 billionths of a meter in diameter.
Genetic material is ss-RNA
HIV exhibits cell tropism for CD4 receptor cells
• The property of particular microorganism to infect a particular cell is called cell
tropism.

4. HISTORY
HIV probably transfers to humans in Africa between 1884 and 1924.
The name “AIDS” – Acquired Immuno Deficiency Syndrome – is created:1982
Montagnier reported causative agent of AIDS & called it LAV:1983
Gallo isolated reterovirus & called it HTLV-III :1983
Scientists identify HIV (initially called HTLV-III or LAV) as the cause of AIDS: 1984
An HIV test is licensed for screening blood supplies :1985
AZT is the first drug approved for treating AIDS :1987
The Joint United Nations Programme on AIDS (UNAIDS) is established :1995

5. Origin
The 'hunter' theory
• The most commonly accepted theory
• SIVcpz was transferred to humans as a result of
chimps being killed and eaten or their blood
getting into cuts or wounds on the hunter.
The oral polio vaccine (OPV) theory
• live polio vaccine needs to be cultivated in living
tissue, and initially it was grown in kidney cells
taken from local chimps infected with SIVcpz.

6. The hepatitis B theory
• chimpanzees, contaminated with numerous viruses,
were used to produce hundreds of hepatitis B vaccine
doses administered to central African Blacks along
with homosexual men.
The conspiracy theory
• A survey carried out in the US, identified a significant
number of African Americans who believe HIV was
manufactured as part of a biological warfare
program, designed to wipe out large numbers of
black and homosexual people.
• Most contradicted theory as thought to be iatrogenic.
• Supports for hepatitis B theory

7. CROSS GENESIS
HIV-2 corresponds to SIVsm, a strain of
the Simian Immunodeficiency Virus
found in the sooty mangabey, which is
indigenous to western Africa.

8. Family
RETEROVIRIDAE
SUB FAMILY
LENTIVIRINAE
Subgroup
LENTIVIRUS

9. Generalized Structure of HIV
 Viral envelope (lipid membrane)
 72 little spikes, which are formed from the
proteins gp120 and gp41
 Matrix, which is made from the protein p17
 Viral core (capsid) is bullet-shaped and is made
from the protein p24
 Three enzymes reverse transcriptase,
integrase and protease
 Two identical strands of RNA.

10. Envelope
Matrix layer
Capsid
Reverse
transcriptase

11. Antigenic variation & diversity
 Highly mutable virus
 Exhibits frequent antigenic variation as well as
differences in other features such as nucleotide
sequences, cell tropism & cytopathology
 Not only are there differences between isolates of HIV
from different places or persons but also between
sequential isolates from same person & even between
those obtained from different site of the same person at
the same time
 This is due to the reverse transcription.
 These hypermutant forms of HIV are known as
"circulating recombinant forms" or CRFs

12. Antigenic structure
 HIV has 3 antigen types:
 Envelope antigen- glycosylated polyproteins & antibodies to
these proteins are always present in the serum of HIV infected
person.
 Core antigen- antibodies to these proteins are also present in
the serum of HIV infected person.
 RT antigen (reverse transcriptase)- antibodies are found in
the patient of AIDS.

13. Groups
Virus Types
(subtypes)
M
(A, B, C, D, F,
G, H, J, K)
O
HIV 1
N
HIV
P
HIV 2 No data

14. Genome of HIV
HIV has following genes
• Genes coding for structural proteins-
• Gag, pol, env
• Genes coding for non structural & regulatory proteins-
• Vif, vpr, tat, rev, vpu, nef
rev
gag vif tat tat nef
pol vpr vpu env

15. Genes coding for structural proteins
 gag- determines the core & shell of the virus
 P17, P 24, P55
 pol- codes for the 3 enzymes found in the core of virus
 Polymerase reverse transcriptase, integrase, protease
 env- determines the synthesis of envelope glycoprotein
gp160
 Gp120, gp41
gag
pol env

16.  Vif- viral infectivity factor gene influences the infectivity of
viral particles.
 Vpr- stimulates the promoter region of virus.
 Tat- trans activating gene which enhances the expression
of all viral genes.
 Rev- regulator of virus gene which enhances the
expression of structural proteins.
 Vpu (HIV1)/ Vpx (HIV2)- enhances the maturation &
release of progeny virus from cells.
 Nef- negative factor gene which downs the replication of
virus. rev
vif tat tat nef
vpr vpu

17. 1. ADSORPTION
2. PENETRATION
3. REVERSE
TRANSCRIPTION
LIFE CYCLE OF

18. 4. INTEGRATION
5. TRANSCRIPTION
6. ASSEMBLY
& RELEASE
LIFE CYCLE OF

19. 1. ADSORPTION
2. PENETRATION
3. REVERSE
TRANSCRIPTION
4. INTEGRATION
5. TRANSCRIPTION
6. ASSEMBLY
& RELEASE
LIFE CYCLE OF

20. HIV and the Immune System
When infection occurs through a mucosal surface, the virus is taken up by
submucosal Langerhans cells, which transport it to the regional lymph nodes,
where it is transmitted to CD4+ T cells
When the virus is introduced directly into the blood stream, it will most likely
be filtered in the spleen, adsorbed by Monocytes, macrophages, and related
cells, which express CD4-like molecules
The preferential infection of macrophages and related cells vs. CD4
lymphocytes depends on the affinity of HIV strains for co-receptors. The
infection of macrophages involves interaction with chemokine receptors
(CCR-5 or CKR-5) while the infection of CD4+ T cells involves the CXCR-4
molecule.

21. The infection of monocytes, macrophages, and
related cells is productive but not cytotoxic, and
the infected cells become a source of persistent
viral infection.
In Humoral immune response, neutralizing
antibodies, which inhibit the infectivity of free
HIV in vitro, directed against epitopes of gp120
and gp41. ADCC-promoting antibodies, are also
potentially protective, which react with gp160.

22. On the negative side, enhancing antibodies, which
react with gp41 antibodies and enhance HIV
infectivity by an unknown mechanism, have also
been demonstrated.
Cell-mediated immune responses involve MHC-I
restricted CD8+ T lymphocytes, which recognize a
variety of epitopes in gag, env, nef, and pol HIV
proteins. Thus, cell-mediated immunity seems able
either to block infection or to reduce viral replication
to levels tolerated by the immune system.

23. Monocytes, macrophages, dendritic
cells
Functional changes in these cells,
also some destruction of TH cells,
Immunosuppressive viral molecules
CD4
receptors TH
CEL Depressed immune response initially to
L HIV later to unrelated microbial antigens
Poor CMI responses neutralizing
antibodies produced plus weak T cell
response
Failure to eliminate infection Loss of control of latently carried
microbes
Virus persists immune defect slowly
increases, virus load increases, Disease ARC/AIDS
patients remains infectious for life

24. Stages of HIV infection
4 stages of HIV infection
Primary: No symptoms at all
Asymptomatic :
• Lasts for an average of ten years
• This stage is free from symptoms
Symptomatic
• The symptoms are mild
• Emergence of opportunistic infections and cancers
AIDS
• The illnesses become more severe leading to an AIDS diagnosis
• Secondary or combined immunodeficiency syndrome

26. Clinical Features of HIV Infection
The natural course of HIV infection is as follows:
1. Seroconversion illness
2. Incubation period
3. AIDS-related complex
or persistent generalized
lymphadenopathy, and

27. 4. AIDS
• Opportunistic
Infections
• Opportunistic Tumors
• Neurological
manifestations
• Dermatological
Manifestations
• Gastrointestinal
Manifestations
• Manifestations in
children and during
pregnancy

28. Opportunistic Infections
 Protozoal  Bacterial
 Pneumocystis carinii  Mycobacterium avium
(now thought to be a fungi) complex
 toxoplasmosis of the brain  Extrapulmonary TB
 crytosporidosis with  Salmonella septicaemia
diarrhoea  multiple or recurrent
pyogenic bacterial infection
 Fungal  Viral
 candidiasis (oesophagus,  CMV
trachea, lungs)  HSV
 crytococcosis, extrapulmonary  VZV
histoplasmosis
 coccidiodomycosis

29.  Opportunistic Tumors
 Burkitt's lymphoma
 Burkitt's-like lymphoma
 Diffuse large B-cell
lymphoma (DLBCL)
 Primary central nervous
system lymphoma Tumours in kaposi’s
sarcoma
 Kaposi’s sarcoma (very
common amongst HIV
patients)
 Hodgkin's disease
 Anal and rectal carcinomas
 Hepatocellular carcinomas
 Head, neck and lung cancer
etc. Enlarged & lobulated
tonsils

30. Neurological Dermatological
manifestations manifestations
• Organic Psychosis And • oral hairy leucoplakia
Complete Dementia
• itching maculopapular
eruption
• Subacute Encephalitis
• Seborrhoeic eczema
• Acute
meningoencephalitis, • allergic exanthemas and acne
like eruptions
Aseptic meningitis • Herpes zoster, Cobdylomata
acuminatum, Verruca vulgaris,
Molluscum contagiosum
• Peripheral neuropathy

31. Immunological abnormalities
Features that Other features
characterizes AIDS
• Lymphopenia • Decreased in vitro
lymphocyte proliferative
• Selective T cell response to antigens
deficiency (T4:T8 • Decreased cytotoxic
ratio inversion) response by T cells & NK
• Decreased delayed cells
hypersensitivity • Decreased antibody
response to new
• Hypergammaglobuline antigens
mia • Altered monocyte
• Polyclonal activation function
of B cells • Elevated level of immune
complexes in serum

32. Epidemiology

33.  The National Family Health Survey conducted between 2005 and 2006
measured HIV prevalence among the general adult population of India
 Age group HIV prevalence (%)
Male Female Total
15-19 0.01 0.07 0.04
20-24 0.19 0.17 0.18
25-29 0.43 0.28 0.35
30-34 0.64 0.45 0.54
35-39 0.53 0.23 0.37
40-44 0.41 0.19 0.30
45-49 0.48 0.17 0.33
Total age 15-49 0.36 0.22 0.28
 NACO showed that by the end of 2005 the total number of reported AIDS
cases in India was 116,905, of which 34,177 were women. Around a third of
these were among people younger than 30 years.
 AIDS is pandemic.

34. Transmission of
HIV
Types of exposure Approximate chance of infection per exposure
Unprotected Sexual intercourse 0.1-1.0%
Blood & blood products >90%
Tissue & organ donation 50-90%
Injection & surgicals 0.5-1.0%
Mother to baby (MTCT) 30%

35. Diagnosis
Mainly 2 laboratory
administration are
employed
• Immunological tests
• Specific tests/ serological tests/
HIV test

36. Immunological tests
Total leukocyte & lymphocyte count<2000/mm³
T cell subset assay- T4:T8 ratio reversed
• CD4+T cell count< 200/mm³
Platelet count-thrombocytopenia
Raised IgG & IgA levels
Diminished CMI by skin tests
Lymph node biopsy

37. Specific tests (HIV test)
Antigen detection
Virus isolation- Coculture
technique
Polymerase chain reaction
Antibody detection: includes
serological tests like
• ELISA/EIA
• Western blot test

38. Prophylaxis
Health education
Protected sexual relationship
Safe blood transfusion
Use of sterile surgical equipments & needles
Replacement feeding & abortion (MTCT)
Public awareness

39. Treatment
Approaches to the treatment of
AIDS includes
The treatment & prophylaxis of
Infections & tumours
General management &
rehabilitation
Immunorestorative measures
Specific anti HIV agents

40.  Specific anti-HIV agents
 Integrase Inhibitors- Isentress
 Entry Inhibitors- Fuzion
 Non-Nucleosides Reverse Transcriptase Inhibitors (NNRTI's)-
Intelence, AZT (Zidovudine) etc.
 Nucleotide Analogs- Vireads
 Protease Inhibitors (PI's)- Prezista
 Nucleoside Reverse Transcriptase Inhibitors (NRTI's)- Retrovir etc.
 Combination Medications- Combivir
 Hydrea - Hydroxyurea

41. HIV vaccines
An AIDS vaccine does not yet exist, but efforts to develop a
vaccine against HIV and AIDS have been underway for many
years
Since 1987, more than 30 vaccine candidates have been
tested
An AIDS vaccine could be effective in either of two ways
• Preventive vaccine
• Therapeutic vaccine

42. Pre exposure: Post-infection:
Preventive vaccine Therapeutic vaccine
Product recombinant Product recombinant
envelope vaccine envelope core protein
Aim: to Aim: to
immunize stimulate the
against HIV immune
infection with system to
molecules redouble its
copied from natural effort
viral surface or to defeat HIV
core

43. Developing an AIDS vaccine is a very
difficult challenge for scientists
• Nobody has ever recovered from HIV infection, so
there is no natural mechanism to imitate
• HIV destroys the immune system cells that are
meant to fight against it
• Soon after infection, HIV inserts its genetic material
into human cells, where it remains hidden from the
immune system
• HIV occurs in several subtypes, each of which is
very different from the others
• Within each subtype, HIV is highly variable and
constantly changing
• There are no good animal models to use in
experiments

44. Microbicide
A microbicide is something designed to destroy microbes
(bacteria and viruses) or to reduce their ability to establish
an infection
A microbicide would share many of the advantages of an
AIDS vaccine
The first microbicide candidates developed were made from
barrier gels, among them nonxoynol-9 and cellulose sulfate.
More recent trials have been testing antiretroviral-based
microbicides, which aim to prevent HIV infection

45. A microbicide could work in at least four different ways:
• Kill or inactivate HIV
• Stop the virus entering human cells
• Enhance the body’s normal defense mechanisms against HIV
• Inhibit HIV replication
It would be especially useful for women
An effective microbicide must be made into a
commodity that people will want to use regularly, such
as a cream, gel or vaginal ring.

46. Agents And Factors Responsible For
Causing AIDS
other than HIV
 AIDS in hemophiliacs relates to the use of corticosteroids and
other immunosuppressive agents to prevent the development of
antibodies.
 The chronic use of medications containing glucocorticoids at
high doses by inhalation caused severe impairment of the
immune defenses of the lungs and the upper respiratory tract.
This led to the infection of the lungs and other organs with
opportunistic microorganisms and the development of cancer

47.  AIDS in Africa results from malnutrition, the consequent release
of endogenous cortisol, and opportunistic diseases. Atrophy in
the thymus and lymphoid tissue in people suffering from
malnutrition has been known since 1925; malnutrition also
impairs T cells functions.
 Kaposi's sarcoma (KS), an AIDS-indicator disease, developed in
HIV -negative patients chronically treated with glucocorticoids
and people suffering from severe malnutrition.

48. Some myths about AIDS
 The virus being transmitted through mosquitoes which have
bitten someone with HIV
 You CAN’T get HIV from coughing or sneezing and certainly not
from swimming pools, showers or toilets
 In southern Africa, there was a belief that if a man has sexual
intercourse with a virgin, it will cure his AIDS

49.  The “gay plague” was seen as God’s disapproval of
homosexuality which is described in the traditional Bible as a sin.
It was the Almighty’s way of punishing gays for their “lewd”
behaviour.
 Many people mistakenly believe that what destroys HIV in the
test tube must also work in the human body. This is one reason
why a number of disinfectants and other chemicals have been
wrongly promoted as cures for AIDS like armenicum, colloidal
silver etc.

50. Current researches on AIDS
National Institute of Medical Research where scientists
have discovered that a gene found in rhesus monkeys can
prevent HIV. The same gene in humans can’t block the
virus but it appears that only one change is needed to
enable it to do so. If this proves to be the case it would be
a remarkable breakthrough in the search for a cure
There are various vaccine treatment strategies. One
involves the injection of so-called "naked" DNA. The DNA
contains genes that code for gag, a viral component
thought to be critical to the development of AIDS

51. Highly Active Anti-Retroviral Therapy (HAART) consists drug mixture
typically contains a nucleoside analog, which blocks genetic replication,
and inhibitors of two enzymes that are critical enzyme in the making of
new virus (protease and reverse transcriptase).
Clinical trials for phase one of the HIV/AIDS vaccine being developed in
India is in final stage upto December 2010 with scientists from
Tuberculosis Research Centre (TRC), Chennai, and National AIDS Research
Institute (NARI), Pune
Second phase of AIDS vaccine trials completed under international
project- Nov.2010
Majority of the current research is focusing on the development of
antiretrovirals and improving their effectiveness.

52. Some key words
 Cell tropism: The property of particular organism to infect a
particular cell is called cell tropism.
 Zoonosis: transmission of pathogens from animals to human
 SIVcpz: Simian immuno virus of chimpanzee
 Seroconversion: conversion of serotypes or antigenic variance
 Antigenic variation: the sequence of changes that occur
frequently in the antigenic structure of the organism.
 Iatrogenic: man-made event
 Cytokines: a soluble substance which can communicate with
other immune cells for the presence of antigens
 Chemokines: chemotactic cytokines

53. References
 www.wikipedia.org
 www.avert.com
 www.originofaids.com
 www.sciencedirect.com
 www.ehealthmd.com
 www.sciencedaily.com
 www.guide4living.com
 Textbook of microbiology- Bhatia & Ichhpujani
 Textbook of microbiology- Ananthnarayana & Paniker
 Immunology- Kuby
 Medical immunology- Gabriel Virella
 A textbook of microbiology- R.C.Dubey

54. Back to
contents