This document provides an overview of HIV and oral manifestations in two parts. Part 1 discusses the terminology, classification, structure, pathogenesis and epidemiology of HIV. It describes how HIV is a retrovirus that infects CD4+ T cells and causes AIDS by destroying the immune system. Worldwide, about 36.9 million people live with HIV. In India, the adult prevalence has declined but there are still an estimated 20.88 lakh people living with HIV. The virus is primarily transmitted through sexual contact and mother-to-child transmission. Part 1 lays the groundwork for understanding HIV and its oral implications, which will be covered in Part 2.

1. HIV & ORAL MANIFESTATIONS
PART 1
Aureus Desouza
21/10/15

2. CONTENTS (PART 1)
1. INTRODUCTION
2. TERMINOLOGIES
3. ORIGIN OF INFECTION
4. CLASSIFICATION OF VIRUS
5. STRUCTURAL ORGANISATION
6. PATHOGENESIS
7. EPIDEMIOLOGY (WORLDWIDE)
8. EPIDEMIOLOGY (INDIA)
9. TRANSMSSION
10.MODE OF TRANSMISSION

3. CONTENTS (PART 2)
1. CLINICAL FEATURES (general)
2. CLINICAL FEATURES (oral)
3. STAGES OF INFECTION (cdc and WHO guidelines)
4. Variation of CD4 count with infections
5. Lab Diagnosis
6. Treatment
7. Approach to a new patient with HIV

4. CONTENTS (PART 2)
8. Approach to a patient on ART
9.Universal precautions
10. Safety precautions to be taken in a dental clinic
11. Control …pertaining to the modes of transmission
12. Worldwide AIDS education programmes
13. Worldwide AIDS screening programmes
14. INDIAN AIDS screening programmes

5. INTRODUCTION
• First recognized in US in 1981 with reports of unexplained opportunistic
infections, including Pneumocystis jirovecii pneumonia and Kaposi’s
sarcoma (KS), among homosexual men in New York and San Francisco
• On the basis of the epidemiologic features, association with the loss of
CD4+ lymphocytes and immunosuppression, and likely infectious cause, a
new human retrovirus was postulated as a causal agent.
Principles and practices of infectious diseases 7th ed. Mandell , Douglas, Benett

6. TERMINOLOGIES
• VIRUS: small infectious agent that replicates only inside the
living cells of other organisms
• Virion: While not inside an infected cell or in the process of
infecting a cell, viruses exist in the form of independent
particles. These viral particles, also known as virions
• RETROVIRUS: A retrovirus is a single-stranded positive-sense
RNA virus with a DNA intermediate

7. ORIGIN OF INFECTION
• Human infection  cross species transmission
• Retroviral infection of humans  Zoonoses that originated in primate-to-
human species-jumping event
• HIV-1 ~ Simian immunodeficiency virus of chimpanzees SIVcpz infecting
chimpanzees in Central Africa (probable source of HIV-1)
• HIV-2~ SIVsm Simian immunodeficiency virus of sooty mangabeys in West
and central Africa

8. LENTIVIRUS & RETROVIRUS
• SIMILARITY Capable of establishing prolonged
asymptomatic infection
• DIFFERENCE  Molecular structure and lack of oncogenic
capability(lentivirus)

9. CLASSIFICATION
1. LENTIVIRUS HIV-1, HIV-2, EIAV (horse), Visna (sheep),
SIVsm
2. ALPHARETROVIRUS ALV(birds), RSV (mouse)
3. BETARETROVIRUS MMTV(mouse), MPMV(primates),
JSRV(sheep)
4. DELTARETROVIRUS (ONCOVIRUS) BLV(cow), HTLV-1, HTLV-2
5. GAMMARETROVIRUS FLAV(cat), MLV(mouse), GaLV(gibbon)
6. EPSILONRETROVIRUS WDSV, WEHV-1, WEHV-2 (fish)
7.SPUMAVIRUS FFV (cat), MSFV(primates), BFV(cow)
REFERENCE: Medical microbiology: A guide to microbial infections: Pathogensis, immunity,laboratory
investigation and control. David Greenwood, Mike Barer, Richard Slack, Will Irwing.18ed
HUMAN RETROVIRUS

10. CLASSIFICATION OF HUMAN
IMMUNODEFICIENCY VIRUS (HIV)
HIV-2 HIV-1
Group M
(Major)
Group N
(Non M and non O)
Group O
(outlier)
Clades A, B, C, D, F, G, H, J, K
Circulating recombinant forms (CRF) : combination of above
subtypes
India , China

11. STRUCTURAL ORGANISATION
• Spherical enveloped virus
• Nucleocapsid icosahedral
• Envelope external spikes 2 envelope proteins gp 120, gp41
• Genome 2 identical ss positive sense RNA copies
• Main genes gag, env, pol

12. STRUCTURAL ORGANISATION
External protein
(major) Transmembrane
Ss positive RNA

13. STRUCTURAL ORGANISATION
Determines core and
shell of virus
p55
P15, p18, p24
Codes for precursor
Cleaves into
Polymerase reverse
transcriptase other
viral proteins
Codes for
Determines synthesis
of envelope
gylcoprotein
gp160
gp120,gp41
Cleaves into
Codes for precursor
HIV 1

14. MAJOR ANTIGENS OF HIV
Gp 120 Spike antigen
Gp 41 Transmembrane pedicle protein
P18 Nucleocapsid protein
P24 Principal core protein
P15,P55 Other core protein
P31,P51,
P66
ENVELOPE ANTIGEN
SHELL ANTIGEN
CORE ANTIGEN
POLYMERASE
ANTIGEN

15. ANTIGENIC VARIATION & MOLECULAR HETROGENEITY
• HIV Highly mutable
• Variability  error prone nature of reverse transcription

16. PATHOGENESIS

17. ATTACHMENT OF VIRION TO HOST CELL
Membrane proteins bind to
receptors on the surface of the
target cells
Entry into the host cell
gp120 binds to receptors on CD4
Molecule of T helper cells and
other antigen presenting cells

18. ATTACHMENT OF VIRION TO HOST CELL
Gp 120 undergoes conformational
change
Facilitating binding of chemokine
inducing co-receptors
CCR5 receptor for chemokines
RANTES, M1P1α, M1P1β
CXCR chemokines SDF1

19. CCR5 expressed by macrophages
and monocytes  R5 virus
CXCR4 expressed by lymphocytes
 strains called  X4 virus
Both R5X4 virus
Fusion of viral envelope with
cellular membrane
Envelopment of the viral particle
into the host cell (with exposure of
hydrophobic domain in gp41
ENVELOPMENT OF VIRION IN HOST CELL

20. INTEGRATION OF PROVIRAL DNA
Once RNA is released into the cytoplasm
Reverse transcriptase acts to form ds DNA
Transported to the nucleus and spliced into
host cell DNA
Hereby this state is called as provirus

21. Synthesis of complementary DNA occurs on the viral RNA using reverse transcriptase (5’->3’)
RNAase H activity of Reverse Transcriptase digests RNA from DNA-RNA hybrid
Reverse Transcriptase then produces a ds DNA from ss DNA
Viral RNA (12-235 bases repeated at each end) after replication DNA(longer repeat
sequence) containing enhancer and promoter sequences that control
Expression of viral genome and sequence for initiation of transcription
Linear ds DNA circularize and then integrates with host DNA

22. Circular viral DNA  integrates with host DNA catalysed by integrase contained by viral
genome
Provirus(Cellular DNA + viral DNA)
Now viral DNA is replicated during cell growth
Replication cycle is completed using normal RNA polymerase II
Synthesis of viral RNA and viral mRNA
Translated to final proteins in virus particle

23. EXPULSION OF VIRIONS
Proteins are synthesized and processed to form virion components
Virions are assembled at the cell membrane where envelope and core proteins have
formed
Virions buds off from the cell
Replicative cycle  completes in 24 hrs
These productive cycle  host cells get destroyed

24. Interaction of gp120 with CD4+ T
cells
Internalization of virion
Uncoating of the virion
Viral RNA
Viral DNA
Unitegrated/ intergrated
Activated CD4+ T cells Inactivated CD4+ T cells
Budding of virus particles, synctial
formation
Cytopathic effect
Quantitative Qualitative

25. Major abnormalities in immune system in AIDS
1. T cell defect:-
1. Lymphopenia
2. Susceptibility to opportunistic infection
3. Susceptibility to neoplasms
4. Decreased cytotoxicity
5. Decreased proliferation in response to mitogens and
soluble antigens
6. Decreased production of interleukin- 2
7. Decreased delayed type of hypersensitivity

26. 2. B- cell defect:-
3. Macrophages/ Monocytes
4. Natural killer cells
1. Decreased production of immunoglobulins
2. Polyclonal activation
3. Hypergammaglobinemia
4. Circulating immune complexes
1. Decreased chemotaxis
2. Decreased cytotoxicity
1. Decreased cytotoxicity

27. EPIDEMIOLOGY(worldwide)
• HIV disease continues to be a serious health issue for parts of
the world
• Worldwide  2 million new cases of HIV in 2014
• About 36.9 million people are living with HIV around the
world, and as of March 2015, around 15 million people living
with HIV were receiving antiretroviral therapy (ART)
• An estimated 1.2 million people died from AIDS-related
illnesses in 2014

28. EPIDEMIOLOGY(worldwide)
• 39 million people worldwide have died of AIDS-related causes
since the epidemic began
• 70% of all people living with HIV in 2014 were living in Sub-
Saharan Africa (heaviest burden of HIV/AIDS worldwide)
• Other regions significantly affected by HIV/AIDS include Asia
and the Pacific, Latin America and the Caribbean, and Eastern
Europe and Central Asia.

29. EPIDEMIOLOGY(INDIA)
• The adult HIV prevalence at national level has continued its
steady decline from estimated level of 0.41% in 2001 through
0.35% in 2006 to 0.27% in 2011. Consistent declines have
been noted among both men and women at national level
http://naco.gov.in/epidemic /fact sheet

30. EPIDEMIOLOGY(INDIA)

31. EPIDEMIOLOGY(INDIA)
• Total PLHIV in India is estimated at 20.88 lakh(17.20 lakh-25.30 lakh) in
2011, of whom children account for 7% (1.45 lakh) of all infections. Of all
HIV infections, 39% (8.16 lakh) are among women

32. TRANSMISSION

33. MODE OF TRANSMISSION
1. SEXUAL TRANSMISSION
49% male-tomale sexual contact. Heterosexual contact accounted for another 32%.(US
2005)
Worldwide: Heterosexual > Homosexual contact

34. MODE OF TRANSMISSION
2. MATERNAL TO FETAL TRANSMISSION
• Infected mother to her fetus during pregnancy, during delivery, or by breast-feeding
• As early as the first and second trimester of pregnancy. Most commonly in the perinatal
period
• Mother-to-child transmissions were 23–30% before birth, 50– 65% during birth, and
12–20% via breast-feeding
• Low CD4 cell count, viral RNA in serum, vit A def inc chances of transmission

35. MODE OF TRANSMISSION
3. DRUG USERS (needles, syringes, the water in which drugs are mixed, or the cotton
through which drugs are filtered)
• The risk of acquiring HIV infection from illicit drug use with sharing of needles from an
HIV-infected source is estimated to be 1:150
• The risk of HIV infection increases with the duration of injection drug use; the
frequency of needle sharing; the number of partners with whom it is shared

36. MODE OF TRANSMISSION
4. OCCUPATIONAL EXPOSURE
• Small, but definite, occupational risk of HIV transmission to health care workers and
laboratory personnel and potentially others who work with HIV-containing materials,
particularly when sharp objects are used
• Potential risk of HIV infection are percutaneous injuries (e.g., a needle stick or cut with
a sharp object) or contact of mucous membrane or nonintact skin (e.g., exposed skin
that is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other
potentially infectious body fluids

37. MODE OF TRANSMISSION
5. TRANSFUSION PRODUCTS
• Transfusions of whole blood, packed red blood cells, platelets, leukocytes,
and plasma are all capable of transmitting HIV infection.
• In contrast, hyperimmune γ globulin, hepatitis B immune globulin, plasma-derived
hepatitis B vaccine, and Rho immune globulin have not been associated with transmission
of HIV infection.
• The procedures involved in processing these products either inactivate or remove the
virus

38. MODE OF TRANSMISSION
• Semen and vaginal are potentially infectious but have not been implicated in
occupational transmission from patients to health care workers
• The following fluids are also considered potentially infectious:
cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid,
and amniotic fluid
• Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not
considered potentially infectious unless they are visibly bloody

39. HIV TRANSMISSION RISK
Type of Exposure Risk per 10,000 Exposures
Blood Transfusion 9,250
Needle-sharing during injection drug
use
63
Percutaneous (needle-stick) 23
Anal intercourse 138
Penile-vaginal intercourse 8
Oral intercourse LOW
Biting 4 negligible Sharing sex toys
negligible
negligible
Spitting negligible
Throwing body fluids (including semen
or saliva)
Negligible
Estimated Per-Act Probability of Acquiring HIV from an
Infected Source, by Exposure Act*
PARENTRAL
SEXUAL
OTHERS
http://www.cdc.gov/hiv/pdf/policies_transmission_risk_factsheet.pdf

40. CONCLUSION
• It is essential to know the history, and
pathogenesis of HIV so as to understand the
diagnosis , treatment

41. REFERENCES
• Principles and practices of infectious diseases 7th ed. Mandell ,
Douglas, Benett
• Harisson’s Principles of internal medicine. 17ed. Fauci, Braunwald,
Kasper, Hauser, Longo, Jameson
• Current Medical Diagnostics and Treatment. 52 ed. 2013.Maxine A.
Papadakis, Stephen J. McPhee, Michael W. Rabow
• Textbook of Oral Medicine. Ravikiran Ongole, Praveen BN
• http://www.cdc.gov
• http://naco.gov.in

42. Thank you