This document discusses the oral manifestations of HIV/AIDS. It describes the classification system used to categorize HIV infections and associated conditions. It outlines the major oral conditions seen in each category, including candidiasis, hairy leukoplakia, Kaposi's sarcoma, and various periodontal diseases. It also discusses how the introduction of HAART (Highly Active Antiretroviral Therapy) reduced AIDS deaths and increased survival times after AIDS diagnosis. Some potential adverse effects of HAART on oral health are also noted.

1. Theme-based Session 4b:8
Dental/Oral
Manifestation of
HIV/AIDS

2.  Epidemiology
 Virology
 Clinical manifestations in the pre-HAART era
 HAART
 Clinical manifestations in the HAART era

4. Summary table on the updated HIV/AIDS situation through
the reporting system updated 30 September 2015
July to September 2015 Cumulative
HIV AIDS HIV AIDS
1. Sex
Male 167 15 6059 1356
Female 22 4 1474 270
2. Ethnicity
Chinese 138 15 5115 1247
Non-Chinese 41 4 2287 379
Unknown 10 0 132 0
3. Route of Transmission
Heterosexual contacts 36 8 2767 911
Homosexual contacts 104 10 2690 430
Bisexual contacts 9 0 318 71
Injecting drug use 3 0 341 62
Blood/blood product
recipients
0 0 84 24
Perinatal 0 0 28 9
Undetermined 37 1 1306 119
4. Total 189 19 7534 1626

5. CHN_narrative_report_2015_Page_08

6. Classification*
 Family Retroviridae
 Characterized by the presence of reverse
transcriptase which is able to transcribe DNA
from RNA
*International Committee on Taxonomy of Viruses

7. HIV subtypes
HIV-1
Group M Group N Group O
A B C
CRFs
Circulating
Recombinant
Forms
K
J
H
G
F
D

8. Risk of HIV transmission by
exposure category

9. Structure
 About 100nm in diameter
 an outer envelope of lipid
 the matrix is made from
the protein p17
 Envelope penetrated by
glycoprotein (gp120 and
gp41)
 The viral core (or capsid) is
usually bullet-shaped and
is made from the protein
p24
 Two molecules of ssRNA
 Several copies of RT,
integrase and protease
http://avert.org.uk/virus.htm#2

11. Classification for HIV infection in
Adolescents & Adults in Hong Kong
CD4+ T-cell
categories
Clinical categories
(A)
Asymptomatic,
acute
(primary) HIV
or PGL
(B)
Symptomatic,
not (A) or (C)
conditions
(C) #
AIDS-indicator
conditions
(1) 500/uL A1 B1 C1
(2) 200-
499/uL
A2 B2 C2
(3) < 200/uL A3 B3 C3

12. Category A
 Asymptomatic HIV
infection
 Persistent generalized
lymphadenopathy
 Acute (primary) HIV
infection
CD4+
T-cell
catego
ries
Clinical categories
(A)
Asymptom
atic, acute
(primary)
HIV or
PGL
(B)
Symptom
atic, not
(A) or (C)
conditions
(C) #
AIDS-
indicator
conditions
(1)
500/uL
A1 B1 C1
(2)
200-
499/uL
A2 B2 C2
(3) <
200/uL
A3 B3 C3

13. Category B
It includes the conditions
listed below which are
however not exhaustive :
 Oropharyngeal candidiasis
 Oral hairy leukoplakia
 Herpes zoster (>1 episode
or >1 dermatome)
 Idiopathic
thrombocytopenic purpura
CD4+
T-cell
catego
ries
Clinical categories
(A)
Asymptom
atic, acute
(primary)
HIV or
PGL
(B)
Symptom
atic, not
(A) or (C)
conditions
(C) #
AIDS-
indicator
conditions
(1)
500/uL
A1 B1 C1
(2)
200-
499/uL
A2 B2 C2
(3) <
200/uL
A3 B3 C3

14. Category C
 Candidiasis, esophageal
 Cytomegalovirus retinitis
 Encephalopathy, HIV-related
 Herpes simplex, chronic ulcer,
bronchitis, pneumonitis or
esophagitis
 Kaposi's sarcoma
 Mycobacterium tuberculosis,
extrapulmonary or
pulmonary/cervical lymph node
(only if CD4 <200/uL)#
 Penicilliosis, disseminated #
 Pneumocystis pneumonia
 Pneumonia, recurrent
#Modification of the CDC 1993 Classification
system : (1) Penicilliosis has been added and
(2) pulmonary or cervical lymph node
tuberculosis included only if CD4 < 200/ul.
CD4+
T-cell
catego
ries
Clinical categories
(A)
Asymptom
atic, acute
(primary)
HIV or
PGL
(B)
Symptom
atic, not
(A) or (C)
conditions
(C) #
AIDS-
indicator
conditions
(1)
500/uL
A1 B1 C1
(2)
200-
499/uL
A2 B2 C2
(3) <
200/uL
A3 B3 C3

15. EC-Clearinghouse classification of the oral
manifestations of HIV disease in adults
Group 1 lesions strongly associated with HIV infection
 Candidiasis
 Erythematous
 Pseudomembranous
 Hairy leukoplakia
 Non-Hodgkin’s lymphoma
 Periodontal disease
 Linear gingival erythema
 Necrotizing gingivitis
 Necrotizing periodontitis

16. Group 2 lesions less commonly associated
with HIV infection
 Bacterial infections
Mycobacterium avium-intracellulare
Mycobacterium tuberculosis
 Melanotic hyperpigmentation
 Necrotizing (ulcerative) stomatitis
 Salivary gland diseases
Dry mouth due to decreased salivary flow rate
Unilateral or bilateral swelling of major salivary glands
 Thrombocytopenic purpura
 Ulceration NOS (not otherwise specified)
 Viral infections
Herpes simplex virus
Human papillomavirus lesions
Condyloma acuminatum
Focal epithelial hyperplasia
Verruca vulgaris
Varicella zoster virus
Herpes zoster
Varicella

17. Group 3 lesions seen in HIV
infection
 Bacterial infections
Actinomyces israelii
Escherichia coli
Klebsiella pneumonia
 Cat-scratch disease
 Drug-reactions
Ulcerative
Erythema multiforme
Lichenoid
Toxic epydemolysis
 Epithelioid (bacillary) angiomatosis
 Fungal infections other than Candida
Cryptococcus neoformans
Geotrichium candium
Histoplasma capsulatum
Mucoraceae (mucurmycosis, zygomycosis)
Aspergillus flavus
 Neurological disturbances
Facial palsy
Trigeminal neuralgia
 Viral infections
Cytomegalovirus
Molluscum contagiosum
 Penicilliosis marneffei?

18. Candidiasis
 Erythematous
 Pseudomembranous
 Hyperplastic
 angular cheilitis
 Pseudomembranous and erythematous variants
are the major types and have been shown to be
indicators of disease progression to AIDS within
about 25 months (Dodd et al. 1991)

19. Hairy Leukoplakia
 First described in 1984.
 Usually found on the lateral margin of the tongue.
 Characterized by whitish vertical corrugations that cannot
be wiped away.
 Definitely diagnosed by the demonstration of EBV within
the lesion.
 The median time to AIDS was 24 months and the median
time to death was 41 months (Greenspan et al. 1987;
Greenspan et al. 1991)

20. Kaposi’s sarcoma
 A rare reticuloendothelial lesion which is usually found on
the lower extremities of Jewish or Mediterranean men
above the age of 60.
 In HIV infection, intraorally, over 90% of the cases
occurred on the hard or soft palate. Another common site is
the gingiva.
 Usually appear as flat patches or nodules and are red and
purplish in colour.
 Recently shown to be caused by HHV8.

21. Linear gingival erythema
 Characterised by a fiery red band along the
gingival margin
 the amount of plaque is disproportional to the intensity
of the inflammation
 does not respond to conventional periodontal therapy

22. Necrotising (ulcerative ) gingivitis
 Involves the destruction of the interdental papillae.
 Ulceration, necrosis and sloughing maybe observed
in acute stage.

23. Necrotising (ulcerative) periodontitis
 Characterised by soft tissue loss with
possible exposure, destruction and
sequestration of bone.
 Usually no deep pockets are found.
 Teeth may become loose and pain is often
described as deep seated.

24. What is HAART?
 Highly Active Antiretroviral Therapy

25. HAART
Previously,
Combinations of NRTIs, NNRTIs and PIs
2 NRTI + 1 NNRTI
2 NRTI + 1 PI
“Since these drugs are administered for
long period of time, three drugs
combinations are used in an attempt to
minimize viral resistance to the drugs,
similar to the way treatment for tuberculosis
was managed” (Ho, 1995).

26. Anti-HIV drugs
 Nucleoside/Nucleotide Reverse Transcriptase
Inhibitors (NRTIs) e.g. AZT, ddC.
 Non-Nucleoside Reverse Transcriptase Inhibitors
(NNRTIs) e.g. NVP, EFV
 Protease Inhibitors (PIs) e.g. RTV, SQV
 Entry Inhibitors e.g. ENF
 Integrase strand transfer inhibitors (INSTI) e.g.
DTG

27. Nucleoside/Nucleotide Reverse
Transcriptase Inhibitors (NRTIs)
 NRTIs contain faulty
versions of the building
blocks (nucleotides) used
by reverse transcriptase to
convert RNA to DNA.
 When reverse transcriptase
uses these faulty building
blocks, the new DNA
cannot be built correctly.
 In turn, HIV's genetic
material cannot be
incorporated into the
healthy genetic material of
the cell and prevents the
cell from producing new
virus.
http://www.aidsmeds.com

28. Non-Nucleoside Reverse
Transcriptase Inhibitors (NNRTIs)
 NNRTIs attach themselves to reverse
transcriptase and prevent the enzyme
from converting RNA to DNA.
 In turn, HIV's genetic material cannot be
incorporated into the healthy genetic
material of the cell, and prevents the cell
from producing new virus.

29. Protease Inhibitors (PIs)
 Once HIV's genetic
material (RNA) is inside a
T-cell's DNA, the cell
produces a long strand of
genetic material that must
be cut up and put together
correctly to form new
copies of the virus.
 Cutting up this strand
requires a scissor-like
enzyme called protease.
 PIs block this enzyme and
prevent the cell from
producing new viruses.
http://www.aidsmeds.com

30. Entry Inhibitors
 Entry inhibitors work by
attaching themselves to
proteins on the surface of T-
cells or proteins on the
surface of HIV.
 Some entry inhibitors target
the gp120 or gp41 proteins
on HIV's surface.
 Some entry inhibitors target
the CD4 protein or the CCR5
or CXCR4 receptors on a T-
cell's surface.
 If entry inhibitors are
successful in blocking these
proteins, HIV is unable to
bind to the surface of T-cells
and gain entry into the cells.
http://www.aidsmeds.com

31. Integrase strand transfer inhibitors (INSTI)
 Block insertion of HIV DNA into CD4 cell
DNA

32. Variable July 1984
to Dec
1989
Jan 1990 to
Dec 1994
Jan 1995 to
June 1998
July 1998
to June
2001
July 2001
to Dec
2003
Therapy
era
No/monothera
py
Monotherapy/c
ombination
HAART
introduction
Short-term
stable HAART
Moderate-term
stable HAART
No. seen 633 660 472 496 464
Median CD4
cell count
at AIDS
diagnosis
(cells/µL)
141 90 196 241 268
Deaths
[No. (%
person-
years)
388 (57%) 445 (49%) 109 (14%) 71 (6%) 44 (4%)
Relative
time
1 1.42 3.57 7.82 10.65
Descriptive statistics, adjusted relative times for survival after an initial AIDS diagnosis in five calendar periods from July 1984 to December 2003.
From: Schneider: AIDS, Volume 19(17).November 18, 2005.2009–2018

33.  In Hong Kong, median survival after AIDS
was diagnosed increased from 29.8
months to more than 70 months.

34. Treatment failure
 Resistance by the virus
 Non-compliance with the drug regime
 Suboptimal potency or blood level of the
drug combination

35. Orofacial Adverse Effects of HAART
 Lipodystrophy syndrome disfigurement
 Recurrent oral ulceration secondary to
neutropenia
 Xerostomia
 Erythema multiforme associated with NRTI
 Mucocutaneous hyperpigmentation
 Dysgeusia, circumoral paresthesia,
cheilitis, xerostomia associated with PIs

36. Lipodystrophy syndrome
 A disturbance of lipid (fat)
metabolism that involves the
partial or total absence of fat and
often the abnormal deposition
and distribution of fat in the body
 characterized by increased fat
pad enlargement (buffalo hump)
and possible breast hypertrophy,
with loss of fatty tissue in the
limbs, buttocks and face. The
nasolabial regions and temples
are the most common sites of
facial involvement. The lips crack.
The abdomen swells producing a
sometimes painful pot belly
 The fat wasting in the limbs leads
to prominence of the
subcutaneous veins while that of
the face and buttocks leads to
marked hollowing and wrinkling
of the skin.
http://www.uspharmacist.com

37. Oral lesions and HAART
 Studies reported a decreased frequency of
HIV-related oral manifestations of 10 to
50%

38. Oral Lesions with decreased prevalence
 Oral candidiasis
 Hairy leukoplakia
 Kaposi’s sarcoma
 Melanotic hyperpigmentation
 Necrotising periodontitis

39. Oral Lesions with increased prevalence
 Oral warts
 HIV-related salivary gland disease

40. Oral lesions and use of antiretroviral therapy. Greenspan et al. The Lancet 2005: 357;1411-2.

55. Difficulties in developing Vaccine
 HIV infects only humans and chimpanzees
 Chimpanzees are scarce, expensive, and do not show
signs of disease when infected.
 Variety of viral subtypes.
 Because distinct HIV subtypes are more prevalent in
certain locations, some scientists have asked whether
HIV vaccines need to be developed specifically for
certain geographical regions.
 HIV's rapid mutation rate and the presence of
multiple viral variants within a given individual.

56. Role of the dental profession in the
management of HIV-infected individuals*
 Orofacial lesions may identify HIV-positive people
 HIV-related oral lesions have been shown to be the first
clinical sign of HIV-infection in both industrialized (oral
candidiasis; hairy leukoplakia) and resource-poor countries
(oral candidiasis; herpes zoster)
 Prognostic significance of HIV-related oral lesions has been
well described in industrialized countries, but is mainly
applicable in resource-poor countries
 Early diagnosis is needed for optimal treatment of HIV-
related oral lesions, in particular lesions such as necrotizing
gingivitis and necrotizing periodontitis
 Diet counseling
*Bulletin of the World Health Organization

57. Infection Control!

59. Salivary glands