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1. HIV & AIDS
DR. GADGIL PADR. GADGIL PA
Assoc. Prof., Dept. of Pathology,Assoc. Prof., Dept. of Pathology,
Dr. V.M. Govt. Medical College, SolapurDr. V.M. Govt. Medical College, Solapur

2. What is HIV & AIDS

H = HumanH = Human

I = ImmunodeficiencyI = Immunodeficiency

V = VirusV = Virus

A = AcquiredA = Acquired

I = ImmunodeficiencyI = Immunodeficiency

D = DiseaseD = Disease

S = SyndromeS = Syndrome

3. AIDS

End stage of spectrum of diseases caused End stage of spectrum of diseases caused
by a virus, HIV, which attacks & by a virus, HIV, which attacks &
weakens ‘Immune system’weakens ‘Immune system’

4. Immune system

Immune system is responsible for our defense Immune system is responsible for our defense
against various bacteria, viruses etc.against various bacteria, viruses etc.

Consist of T lymphocytes & B lymphocytesConsist of T lymphocytes & B lymphocytes

HIV virus attacks & destroys T cellsHIV virus attacks & destroys T cells

The effect is failure of T cell defense & the The effect is failure of T cell defense & the
individual is susceptible for various individual is susceptible for various
infections, in our country most common is infections, in our country most common is
T.B.T.B.

5. Acquired Immunodeficiency Acquired Immunodeficiency
Syndrome (AIDS)Syndrome (AIDS)
HistoryHistory

1950s1950s: Blood samples from Africa have HIV : Blood samples from Africa have HIV
antibodies.antibodies.
19761976: First : First knownknown AIDS patient died.AIDS patient died.
19801980: First human retrovirus isolated (HTLV-1).: First human retrovirus isolated (HTLV-1).
19811981: First reports of “Acquired Immuno-: First reports of “Acquired Immuno-
deficiency Syndrome” in Los Angeles.deficiency Syndrome” in Los Angeles.
19831983: Virus first isolated in France: Virus first isolated in France ( (LAVLAV).).
19841984: Virus isolated in the U.S. (called: Virus isolated in the U.S. (called HTLV-IIIHTLV-III
and AIDS-Related Virus,and AIDS-Related Virus, ARVARV).).

19851985: Development and implementation of : Development and implementation of
antibody test to screen blood donors.antibody test to screen blood donors.

6. Acquired Immunodeficiency Acquired Immunodeficiency
Syndrome (AIDS)Syndrome (AIDS)
History (Continued)History (Continued)

19861986: : Consensus name Human Immunodeficiency Consensus name Human Immunodeficiency
Virus (HIV-1). Virus (HIV-1).
Related virus (HIV-2) identified.Related virus (HIV-2) identified.
19921992: : AIDS becomes the leading cause of death AIDS becomes the leading cause of death
among adults ages 25-44 in the U.S.among adults ages 25-44 in the U.S.
1997: 1997: Mortality rates of AIDS starts to decline due Mortality rates of AIDS starts to decline due
to the introduction of new drug cocktails.to the introduction of new drug cocktails.
20012001: World Health Organization predicts up to : World Health Organization predicts up to
40 million infected individuals. More than 22 40 million infected individuals. More than 22
million have already died.million have already died.

7. 25 years of AIDS25 years of AIDS
9In 1991-1993, HIV prevalence in
young pregnant women in Uganda
and in young men in Thailand
begins to decrease, the first major
downturns in the epidemic in
developing countries
10 Highly Active Antiretroviral
Treatment launched
11 Scientists develop the first
treatment regimen to reduce
mother-to-child transmission of HIV
12 UNAIDS is created
13 Brazil becomes the first developing
country to provide antiretroviral
therapy through its public health
system
14 The UN General Assembly Special
Session on HIV/AIDS. Global Fund
to fight AIDS, Tuberculosis and
Malaria launched
15 WHO and UNAIDS launch the "3 x 5"
initiative with the goal of reaching 3
million people in developing world
with ART by 2005
16 Global Coalition on Women and
AIDS launched
40
30
20
10
0
50
35
25
15
5
45
M
illio
n
1980 1985 1990 1995 2000 2005
1234
5
6
8
9
11
12
13
14
15
16
7
10
1 First cases of unusual immune deficiency are identified
among gay men in USA, and a new deadly disease
noticed
2Acquired Immune Deficiency Syndrome (AIDS) is
defined for the first time
3 The Human Immune Deficiency Virus (HIV) is
identified as the cause of AIDS
4 In Africa, a heterosexual AIDS epidemic is
revealed
5 The first HIV antibody test becomes
available
6 Global Network of People living with
HIV/AIDS (GNP+) (then International
Steering Committee of People Living
with HIV/AIDS) founded
7 The World Health Organisation
launches the Global Programme on
AIDS
8 The first therapy for AIDS –
zidovudine, or AZT -- is
approved for use in the USA
People People
living living
with with
HIVHIV
Children Children
orphaned orphaned
by AIDS in by AIDS in
sub-sub-
Saharan Saharan
AfricaAfrica
1.1

8. Estimated number of people living with HIV
in Asia, 1986–2006
0
2
4
6
8
10
M
illio
n
Number
of people
living
with HIV
1986 1992 1996 2006
Year
19881990 1994 200219982000 2004

9. People Living with HIV/AIDS by End of 2001
North America
950,000
Latin America
1.5 million
Western Europe
560,000
East Europe & Central Asia
1’000,000
Sub-Saharan Africa
28.5 million
North Africa &
Middle East
500,000
Australia &
New Zealand
15,000
South/South East Asia
5.6 million
East Asia & Pacific
1’000,000
Total: 40 million people
Caribbean
420,000

10. HIV/ AIDS & Present status of
India

WHO estimates 4.5 WHO estimates 4.5
million people are million people are
infected by HIV in infected by HIV in
INDIAINDIA

11. AIDS Epidemiological Factors

AGENT: HIV virus, 2 types HIV I & AGENT: HIV virus, 2 types HIV I &
HIV II, in India it is HIV IHIV II, in India it is HIV I

Reservoir of Infection: HumanReservoir of Infection: Human

Source of infection: Blood, semen, Source of infection: Blood, semen,
vaginal fluid are main sourcesvaginal fluid are main sources

12. AIDS Epidemiological Factors

Host factorsHost factors

Age & Sex: 15 to 24 yearsAge & Sex: 15 to 24 years

High risk groups: a) Presence of sexually High risk groups: a) Presence of sexually
transmitted diseases b) frequency of transmitted diseases b) frequency of
unprotected exposure c) High risk unprotected exposure c) High risk
partners d) Population receiving repeated partners d) Population receiving repeated
blood transfusion e) High risk mother for blood transfusion e) High risk mother for
a child a child

13. AIDS Epidemiological Factors

Other factors: Other factors:

war & civil disturbanceswar & civil disturbances

Social unacceptance of condomSocial unacceptance of condom

Women statusWomen status

Low literacyLow literacy

UrbanizationUrbanization

imprisonmentimprisonment

Drug & alcohol abuseDrug & alcohol abuse

High mobility like truck driversHigh mobility like truck drivers

14. Structure
SPHERICAL
ELECTRON DENSE
CONE SHAPED CORE
LIPID ENVELOPE
CORE: P 24, P7/9, 2
COPIES RNA, 3
ENZYMES
PROTEASE, RT & INTEGRASE

17. Structure of the Human Immunodeficiency Virus
HIV is a Retrovirus

18. Genome

19. Genome

LTR: control regions that bind with transcription factors, LTR: control regions that bind with transcription factors,
required for initiation of transcriptionrequired for initiation of transcription

Vif: Viral infectivity factorVif: Viral infectivity factor

Vpu: promotes CD4 degradationVpu: promotes CD4 degradation

Env: gp 160 which is cleaved in ER in gp 120 & gp 41Env: gp 160 which is cleaved in ER in gp 120 & gp 41

Nef: negative effector p24, blocks apoptosis, enhances virion Nef: negative effector p24, blocks apoptosis, enhances virion
infectivityinfectivity

Gag pr 55: Polyprotein processed by viral protease that forms Gag pr 55: Polyprotein processed by viral protease that forms
p17, p24, p7p17, p24, p7

Pol: for various enzymesPol: for various enzymes

Vpr: Facilitates infection of microphagesVpr: Facilitates infection of microphages

Tat: Transcriptional activatorTat: Transcriptional activator

20. Life Cycle of HIVLife Cycle of HIV
1. Attachment: 1. Attachment: Virus binds to surface Virus binds to surface
molecule (CD4) of T helper cells and molecule (CD4) of T helper cells and
macrophages.macrophages.

CoreceptorsCoreceptors: : Required for HIV infection. Required for HIV infection.

CXCR4CXCR4 and and CCR5CCR5 mutants are resistant to mutants are resistant to
infection.infection.
2. Fusion2. Fusion: Viral envelope fuses with cell : Viral envelope fuses with cell
membrane, releasing contents into the membrane, releasing contents into the
cell.cell.

22. HIV Life Cycle: Attachment Requires CD4
Receptor plus a Coreceptor

23. Life Cycle of HIVLife Cycle of HIV
3. Reverse Transcription3. Reverse Transcription: : Viral RNA is Viral RNA is
converted into DNA by unique enzyme converted into DNA by unique enzyme
reverse transcriptasereverse transcriptase..
Reverse transcriptaseReverse transcriptase
RNA ---------------------> DNARNA ---------------------> DNA
Reverse transcriptase is the target of Reverse transcriptase is the target of
several HIV drugs: AZT, ddI, and ddC.several HIV drugs: AZT, ddI, and ddC.

24. HIV Life Cycle: Reverse Transcriptase
Converts RNA into DNA

25. Life Cycle of HIVLife Cycle of HIV
4. Integration4. Integration: Viral DNA is inserted into host cell : Viral DNA is inserted into host cell
chromosome by unique enzyme chromosome by unique enzyme integraseintegrase. .
Integrated viral DNA may remain latent for years Integrated viral DNA may remain latent for years
and is called a and is called a provirusprovirus..
5. Replication5. Replication: Viral DNA is transcribed and RNA : Viral DNA is transcribed and RNA
is translated, making viral proteins. is translated, making viral proteins.
Viral genome is replicated.Viral genome is replicated.
6. Assembly:6. Assembly: New viruses are made. New viruses are made.
7. Release:7. Release: New viruses bud through the cell New viruses bud through the cell
membrane.membrane.

27. HIV Life Cycle: Latent versus Active
Infection

28. HIV Life Cycle: Latent versus Active
Infection in Macrophages

29. Strains: Based on tropism

M tropic: Use CCR5 coreceptor. M tropic: Use CCR5 coreceptor.
Expressed on both monocytes and T Expressed on both monocytes and T
cellscells

T tropic strain: Use CCR4. expressed on T tropic strain: Use CCR4. expressed on
only T cellsonly T cells

30. Transmission of AIDS (Worldwide)Transmission of AIDS (Worldwide)
1.1. Sexual contact with infected individual:Sexual contact with infected individual: All All
forms of sexual intercourse (homosexual and forms of sexual intercourse (homosexual and
heterosexual). 75% of transmission.heterosexual). 75% of transmission.
2. Sharing of unsterilized needles by 2. Sharing of unsterilized needles by
intravenous drug users and unsafe medical intravenous drug users and unsafe medical
practices: practices: 5-10% of transmission. 5-10% of transmission.
3. Transfusions and Blood Products:3. Transfusions and Blood Products:
Hemophiliac population was decimated in Hemophiliac population was decimated in
1980s. Risk is low today. 3-5% of 1980s. Risk is low today. 3-5% of
transmission. transmission.
4. Mother to Infant (Perinatal):4. Mother to Infant (Perinatal): 25% of 25% of
children become infected in utero, during children become infected in utero, during
delivery, or by breast-feeding (with AZT only delivery, or by breast-feeding (with AZT only
3%). 5-10% of transmission. 3%). 5-10% of transmission.

31. HIV Does Not Spread By:

TouchTouch

HuggingHugging

Hand shakeHand shake

Using same utensilsUsing same utensils

Sharing towels or shirts or trousersSharing towels or shirts or trousers

32. Does It Spreads By Mosquito
Bite?

NONO

Because the virus cannot survive & grow Because the virus cannot survive & grow
in salivary glands of mosquitoin salivary glands of mosquito

33. Does It Spreads By Sharing
Shaving Kits?

NONO

But always use separate blade because But always use separate blade because
other skin diseases can be transmittedother skin diseases can be transmitted

34. Does It Spreads By Contact With
Urine Or Stool Of Patient?

NONO

In urine & stool number of virus is very In urine & stool number of virus is very
low & no such incidence has been low & no such incidence has been
reported in the world till date.reported in the world till date.

SO THERE SHOULD BE NO FEAR SO THERE SHOULD BE NO FEAR
ABOUT PATIENT CAREABOUT PATIENT CARE

35. HIV SPREAD REAL FACTS

Does it spread via sexual intercourse Does it spread via sexual intercourse
with infected person?with infected person?

YES YES

If the partner is HIV infected it will If the partner is HIV infected it will
spread via semen or vaginal secretionsspread via semen or vaginal secretions

36. HIV SPREAD REAL FACTS

DOES IT SPREAD BY DOES IT SPREAD BY
HOMOSEXUAL CONTACT?HOMOSEXUAL CONTACT?

YESYES

During homosexual intercourse there is During homosexual intercourse there is
always chance of injury to genital organs always chance of injury to genital organs
so spread can occur.so spread can occur.

37. HIV SPREAD REAL FACTS

HIV spreads only by repeated sexual HIV spreads only by repeated sexual
contacts?contacts?

REMEMBER EVEN SINGLE REMEMBER EVEN SINGLE
CONTACT WITH INFECTED CONTACT WITH INFECTED
PERSON IS SUFFICIENT TO PERSON IS SUFFICIENT TO
SPREAD THE DISEASESPREAD THE DISEASE

38. HIV SPREAD REAL FACTS

Whether Condom is 100% Protective?Whether Condom is 100% Protective?

It’s better not to have unsafe sex because It’s better not to have unsafe sex because
there is always a chance of condom tear.there is always a chance of condom tear.

Compare with helmetCompare with helmet

39. HIV Transmission in United States
and Rest of the World

40. Stages of HIV Infection

41. Stages Of HIV Infection

Primary stage: Dissemination in Lymph node Primary stage: Dissemination in Lymph node
& spill over in body 2 to 3 weeks after & spill over in body 2 to 3 weeks after
infection Flu like symptoms Followed by infection Flu like symptoms Followed by
generalized lymphadenopathy generalized lymphadenopathy

Chronic Stage/ Latent period: 8 to 10 years. Chronic Stage/ Latent period: 8 to 10 years.
Virus remains silent in the cells of the Virus remains silent in the cells of the
lymphnode. Asymptomatic Patient appears lymphnode. Asymptomatic Patient appears
healthyhealthy

AIDSAIDS

42. Laboratory Test

ELISAELISA

Spot testSpot test

W.BW.B

PCRPCR

43. Antibody Levels, T Cell Counts, and
HIV Concentration After Infection

44. Course of Progression In HIV
Infection

3 Patterns3 Patterns

A) Typical Progressors: 80 to 90 % Infection A) Typical Progressors: 80 to 90 % Infection
> 3 to 6 weeks > Flu like illness > Clinical > 3 to 6 weeks > Flu like illness > Clinical
normal 8 to 10 years > Clinically apparent normal 8 to 10 years > Clinically apparent
disease > Death Survival 10 yearsdisease > Death Survival 10 years

B) Rapid Progressors: 5 to 10 % AIDS within B) Rapid Progressors: 5 to 10 % AIDS within
2 to 3 years after seroconversion 2 to 3 years after seroconversion

C) Long term non progressors: 5%C) Long term non progressors: 5%

45. AIDS defining Opportunistic infections
& neoplasms

Protozoal and helminthic.. Cryptosporidiasis, Protozoal and helminthic.. Cryptosporidiasis,
pneumocystosis, toxoplasmosispneumocystosis, toxoplasmosis

Fungal- candidiasis, cryptoco., Fungal- candidiasis, cryptoco.,
coccidiodomy., histoplasm.coccidiodomy., histoplasm.

Bacterial: Mycobacte., Nocardiosis, Bacterial: Mycobacte., Nocardiosis,
SalmonellaSalmonella

Viral: CMV, HS, VZViral: CMV, HS, VZ

Neoplasm: KS, B cell NHL, Primary CNS Neoplasm: KS, B cell NHL, Primary CNS
lymphoma, Ca Cxlymphoma, Ca Cx

46. Kaposi sarcoma - Clinical presentation and medium power

47. Brain, CNS lymphoma - Medium power

48. Brain, Toxoplasma encephalitis - Medium power

49. Colon, cytomegalovirus (CMV) infection - Low power

50. AIDS Associated Disease CategoriesAIDS Associated Disease Categories
1. Gastrointestinal: 1. Gastrointestinal: Cause most of illness and death Cause most of illness and death
of late AIDS. of late AIDS.
SymptomsSymptoms::

DiarrheaDiarrhea

Wasting (extreme weight loss)Wasting (extreme weight loss)

Abdominal painAbdominal pain

Infections of the mouth and esophagus. Infections of the mouth and esophagus.
PathogensPathogens: : CandidaCandida albicansalbicans, cytomegalovirus, , cytomegalovirus,
Microsporidia, and Cryptosporidia.Microsporidia, and Cryptosporidia.

51. African AIDS patient with slim disease
Source: Tropical Medicine and Parasitiology, 1997

52. Opportunistic Oral Yeast Infection by
Candida albicans in an AIDS Patient
Source: Atlas of Clinical Oral Pathology, 1999

53. AIDS Associated Disease CategoriesAIDS Associated Disease Categories
2. Respiratory: 2. Respiratory: 70% of AIDS patients develop 70% of AIDS patients develop
serious respiratory problems.serious respiratory problems.
Partial list of respiratory problems associated with AIDS: Partial list of respiratory problems associated with AIDS:


BronchitisBronchitis

PneumoniaPneumonia

TuberculosisTuberculosis

Lung cancerLung cancer

SinusitisSinusitis

PneumonitisPneumonitis

54. Chest X-Ray of AIDS Patient with Tuberculosis

55. AIDS Associated Disease CategoriesAIDS Associated Disease Categories
3. Neurological:3. Neurological: Opportunistic diseases and Opportunistic diseases and
tumors of central nervous system.tumors of central nervous system.
Symptoms many include: Headaches, peripheral Symptoms many include: Headaches, peripheral
nerve problems, and nerve problems, and AIDS dementia complexAIDS dementia complex
(Memory loss, motor problems, difficulty (Memory loss, motor problems, difficulty
concentration, and paralysis).concentration, and paralysis).

56. AIDS Associated Disease CategoriesAIDS Associated Disease Categories
4. Skin Disorders:4. Skin Disorders: 90% of AIDS patients develop 90% of AIDS patients develop
skin or mucous membrane disorders.skin or mucous membrane disorders.

Kaposi’s sarcomaKaposi’s sarcoma
•1/3 male AIDS patients develop KS1/3 male AIDS patients develop KS
•Most common type of cancer in AIDS patientsMost common type of cancer in AIDS patients

Herpes zoster (shingles)Herpes zoster (shingles)

Herpes simplexHerpes simplex

ThrushThrush

Invasive cervical carcinomaInvasive cervical carcinoma
5. Eye Infections: 5. Eye Infections: 50-75% patients develop eye 50-75% patients develop eye
conditions.conditions.

CMV retinitisCMV retinitis

ConjunctivitisConjunctivitis

Dry eye syndromeDry eye syndrome

57. Extensive tumor lesions of Kaposis’s sarcoma in AIDS patient.
Source: AIDS, 1997

58. Chronic Herpes Simplex infection with lesions on tongue and lips.
Source: Atlas of Clinical Oral Pathology, 1999.

59. Non-Hodgkin’s Lymphoma & ascites in AIDS patient
Source: Tropical Medicine and Parasitiology, 1997

60. Drugs Against HIVDrugs Against HIV
Reverse Transcriptase Inhibitors: Reverse Transcriptase Inhibitors: Competitive Competitive
enzyme inhibitors. Example: AZT, ddI, ddC.enzyme inhibitors. Example: AZT, ddI, ddC.
Protease InhibitorsProtease Inhibitors: Inhibit the viral proteases. : Inhibit the viral proteases.
Prevent viral maturation.Prevent viral maturation.
Problem with individual drug treatments: Problem with individual drug treatments:
Resistance.Resistance.

Drug CocktailsDrug Cocktails: A combination of:: A combination of:

One or two reverse transcriptase inhibitorsOne or two reverse transcriptase inhibitors

One or two protease inhibitors.One or two protease inhibitors.
Drug cocktails have been very effective in Drug cocktails have been very effective in
suppressing HIV replication and prolonging the suppressing HIV replication and prolonging the
life of HIV infected individuals, but long term life of HIV infected individuals, but long term
effectiveness is not clear.effectiveness is not clear.

61. Perinatal Transmission of AIDS
Source: Tropical Medicine and Parasitiology, 1997