HIV

Dewi Agustini – 040001600033

Faculty of Dentistry
Trisakti University
References

 Goering RV, Dockrell HM, Zuckerman M, Roitt IM, Chiodini PL. Mim’s Medical Microbiology,
5th Ed. China: Elsevier; 2013; p27-267.
 Greenwood D, Barer M, Slack R, Irving W. Medical Microbiology, 18th Ed. China: Churchill
Livingstone; 2012; p82-576.
 Lu W, Mehraj V, Vyboh K, Cao W, Li T, Routy J-P. CD4:CD8 ratio as a frontier marker for
clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed
HIV-positive patients. Journal of the International AIDS Society. 2015;18(1):20052.
doi:10.7448/IAS.18.1.20052.
 Neville BW, Damm DD, Allen CM, Chi AC. Oral and Maxillofacial Pathology, 4th Ed. Canada:
Elsevier; 2016; p239-254.
 Scully C. Scully’s Medical Problem in Dentistry, 7th Ed. China: Churchill Livingstone; 2014;
p498-514.
 Scully C. Oral and Maxillofacial Medicine – The Basis of Diagnosis and Treatment, 3rd Ed.
China: Churchill Livingstone; 2013; p346-350.
 Shafer, Hina, Levy. Shafer’s Textbook of Oral Pathology, 7th Ed. R Rajendran and B
Sivapathasundharam: Editors. New Delhi: Elsevier; 2012; p357-363.
DISCOVERY AND EPIDEMIC
DISCOVERY AND EPIDEMIC

 In 1981, CDC noted an increase in requests to use pentamidine for

Pneumocystis jirovecii infection in previously well individuals who also
suffered severe infections by other normally harmless microorganisms
 Patients had evidence of impaired immune function
 Skin test anergies
 Depletion of CD4+ T-helper lymphocytes
 This immunodeficiency syndrome appearing in an individual without a
known cause was referred to as ‘acquired immune deficiency syndrome’
(AIDS)
 HIV, the causative virus of AIDS, was isolated from blood lymphocytes in
1983
DISCOVERY AND EPIDEMIC

 Believed to existed firstly in Africa around 1950s

 Appears to have originated from an epicenter in sub-Saharan Africa,
probably Zaire and Cameroon
 Rate of increase has slowed in most parts of the developed word
 Little if any difference in gender affected by HIV
 Worldwide has spread mainly via heterosexual sex, although the
incidence is still especially high in men who have sex with men (MSM)
 Is of major concern in CIS and Asia
DISCOVERY AND EPIDEMIC

 By the end of 2009, about 35 million adults and children were infected
with HIV including:
 22.5 million in sub-Saharan Africa
 5 million in South, South-East and East-Asia
 1.4 million in Eastern Europe and Central Asia
 1.5 million in North America
 0.8 million in Western and Central Europe
PROPERTIES OF HIV
HIV (Human Immunodeficiency Virus)

 Is a retrovirus, so-called because this single-stranded RNA virus contains

a pol gene that codes for a reverse transcriptase (Latin: retro,
backwards)
 Formerly named human T lymphotropic virus III (HTLV-III)
 HIV can survive for:
 Up to 15 days at room temperature
 10-15 days at 37°C
 Is inactivated 100-fold each our at temperature above 60°C
HIV (Human Immunodeficiency Virus)

Capsid
Virus family Virus genus Envelope
symmetry

• Retrovirida • Lentivirus • Yes • Icosahedral

e type III
Molecular
RNA
Particle size weight of Sub-species
Structure
RNA

• 80-120 nm • 7 x 10-6 g • ss linear • HIV-1

HIV Sub-species

HIV-1
 Is by far the most common
worldwide
 Separated into 3 groups:
 M (main)  subtypes A to J
 N (new)  focused in western
central Africa
 O (outlier)  focused in
western central Africa
HIV-2
 Originated from West Africa,
probably arose from primate
viruses
 Antigenically distinct from HIV-1
 Less pathogenic
PATHOGENESIS OF HIV INFECTION
Predisposing Factors and Transmission
 HIV is present in tissues and body  Rare way of transmission:
fluids, transmitted mostly where
the viral load is high
 Common way of transmission:
 Sharing needles and/or
syringes
 Unprotected sexual intercourse
with an infected person
 Babies born to HIV-infected
mother, before or during birth,
and breastfeeding
 Blood transfusions
 Rarely in the healthcare setting
 Rarely by saliva, presumably
because of protection from
salivary:
 SLP-1
 Peroxidases
 Thrombospondin-1
 HBD-2 and -3
 Salivary chemokines : CCL2,
CCL4, CCL5, and CCL11
 Virus and Host Cell Interaction

Penetration Replication Release

•Virus attached to •Envelope breaks and •Integration of viral
receptor(s) at host •Virus or its genome viral genome is •Synthesis of viral particles •New viruses are
cell membrane enters the cytoplasm within the cytoplasm macromolecules released and host
cell lysis
Attachment
Uncoating Assembly
(adsorption)
Viral Adsorption

 More than 80% of transmission involves mucosal surfaces, in particular

cervicovaginal, penile, and rectal.
 The remainder: intravenous or percutaneous route
 Window period of virus is 7-21 days, as HIV multiplies in the mucosa
and draining lymphoreticular tissues
 First target of HIV: CD4 receptor-bearing cells (Th cells, Langerhans cells
and other dendritic cells, and microglia)
 Macrophages are not as good targets compared with the others
Viral Penetration

 First, the viral gp120 binds to CD4+ , then interacts with a second (co-)
receptor  host cell’s chemokine receptor, namely CCR5-ß or CXCR4-α
 CD4 molecule acts as a high-affinity binding site for the viral gp120
envelope glycoprotein
 Cell susceptibility to infection is therefore affected by the levels of these
chemokine co-receptors
 Their expression may be up-regulated by opportunistic infections
Viral Replication

 Replication and cell destruction occurs when Th is activated

 Respond to HIV antigens
 Secondary microbial infection
 The viral +ve sense transcripted into circular DNA with reverse
transcriptase
 Circular DNA integrates into the host cell DNA  provirus (stable)
 As the DNA of the cell is replicated during cell growth, so the viral DNA
is also replicated
 Replication cycle is completed using the normal cellular RNA pol. II to
synthesize viral RNA and viral mRNAs  virus particle
Host Defense Against HIV

 During the first few months virus-specific CD8+ T cells are formed and
reduce the viremia (HIV load)  appearance of neutralizing antibodies
 Even so, up to 1010 infectious virus particles and up to 109 infected
lymphocytes are produced daily
 Immune system begin to suffer gradual damage  number of
circulating CD4+ T cells steadily falls and HIV load rises
 Skin test DTH responses are absent
 NK cells and Tc cells activity is reduced
 Reduced in IL-2 and IFN-γ production
 As AIDS develops, response to HIV and unrelated antigens are further
depressed
Mechanism of Immunosuppression in HIV

 The exact mechanism is still unclear

 Factors need to be considered:
 Th cells directly killed by virus
 Th cells undergo apoptosis induced by virus
 Th cells made vulnerable to immune attack by Tc cells
 T-cell replenishment impaired by damage to the thymus and lymph
nodes and by infection of stem cells
 Defects in antigen presentation associated with infection of dendritic
cells
 Immunosuppresive virus-coded molecules (gp120, gp41)
DIAGNOSTIC AIDS FOR HIV INFECTION
Diagnosis of HIV Infection

Virus-based Test Anti-HIV Antibody Test

 Viral culture  ELISA/immunofluorescence
 RT-qPCR  Western Blot analysis
 p24 antigen detection
 bDNA
 NASBA
 RT + ELISA
Viral Culture

 Directly detects the virus and hence is highly specific

 It is positive, even during the window period and during the terminal
phase when viral load is high and when the ELISA may be negative
 Takes 2-4 weeks for results
 With the availability of PCR, HIV culture is not done routinely anymore
RT-qPCR (Real-time quantitative Polymerase Chain
Reaction)

 Enzymes (0,5 µL/rx.) : thermis aquaticus (taq) DNA polymerase or

pyrococcus furiosus (pfu) DNA polymerase
 The viral RNA is converted first to cDNA with reverse transcriptase, then
cDNA will be used as template for PCR reaction
 The chemical reaction results (24-28 hrs) will be used to count the viral
RNA (nucleic acid amplification)
 High sensitivity (50 copies/mL)
 Highly useful for prenatal diagnosis of HIV infection and monitoring
host response towards cART
 Require high-end tech and high cost
RT-qPCR Amplification Conditions

Process Time (mins) Temperature (°C) Cycle

Reverse 3 57 1 cycle
transcription 30 42
3 95
Amplification 0,5 94 35 cycles
0,5 58
0,5 72
5 72 1 cycle
p24 Antigen Detection

 Detectable during window period and the late phase of infections when
the virus is replicating rapidly
 Oftenly not detectable as viral replication is low  not sensitive enough
to be of use for routine diagnosis
 Useful in blood banks where the p24 antigen, along with ELISA, can
shorten the window period of diagnosis to less than two weeks
bDNA (Branched DNA) Assay

 Uses a substance that produces light when it combines with HIV

particles
 The amount of light is measured and converted to a viral count
 Has a lower detection limit of 50 copies/ml and an upper limit of
500,000 copies/mL
 This assay can also be used for clades A, B, C, D, E, and G
 Has the advantage of less risk of contamination than PCR
NASBA (Nucleic Acid Sequence-based Amplification)

 Is a primer-dependent technology that can be used for the continuous

amplification of nucleic acids in a single mixture at one temperature
 Product: antisense (ssRNA)
 The main advantage of this technique is that it works at isothermal
conditions (41°C)
 Enzyme Cocktail (5 µL/rx.) : (1) AMV-RT, (2) RNase H, and (3) T7 DdRp
 NASBA has been shown to give faster results than PCR and can, in
addition, also be more sensitive
RT + ELISA

 Is an ELISA-based method of determining viral load by measuring

reverse transcriptase (RT) activity
 Can be done at simple laboratory environments
 The RT assay had 100% sensitivity in detecting viral load equal to or
greater than 400 copies/mL
 Has a low positive predictive value (86% compared to RNA PCR and
70% as compared to bDNA) in groups with a low prevalence of virologic
failure
 The RT assay can be done at 15% of the cost of other assays
 1mL of blood could be used when doing the RT assay in children
Enzyme Link Immunosorbent Assay (ELISA)

 More popular and widely done

 Nearly 99% sensitivity and specificity, esp. on repeated testing
 Much cheaper than PCR and culture, can be done at any center
 In West, it is mandatory to do a Western blot, if the ELISA is positive,
before confirming a person as HIV-positive
 According to WHO, it is not necessary to do a Western blot  repeating
one or two more ELISA tests, using different kits on repeated blood
samples
 Not useful in early diagnosis for newborn (min. 18 months old)
 Is negative during window period and late phase of infection  PCR
Western Blot Analysis

 Detects specific antibodies and show them as separate bands on gels

 More specific than ELISA
 It is interpreted as positive if at least two of three bands (p24, gp41,
gp120/160 bands) are positive; if none, it is labeled as negative
 When test is indeterminate, one needs to repeat both ELISA and
Western blot once or twice after 4-6 weeks until it becomes definitely
positive or negative
 Also negative during window period and late phase of infection  PCR
 Not useful for early diagnosis in newborn (min.18 months old)
Immunological Tests and Surrogate Markers

 CD4+T cell count, CD4+T cell % and CD4/CD8 ratio are tests done to
determine immune status
 A gradual decline in CD4+T cell count suggests disease progression
 CD4+T cell % is more constant whereas absolute CD4 is age
dependent
 Normal uninfected adult : 2.11+ 0.99
 Recently infected : 0.7 + 0.47
 Advanced patient : 0.1 + 0.05
 cART responsive patients : 1.13 + 0.59
 It helps to prognosticate, monitor disease progression and to determine
response and relapse following antiretroviral drug therapy
Salivary Tests

 Specimen : saliva and gingival crevicular fluid (GCF)

 The immunoglobulin content of oral fluids is similar to that of blood,
but their levels are lower
 However, the use of an HIV IgG antibody capture assay (GAC ELISA),
designed specifically for testing oral fluids, has produced encouraging
results
 A number of studies, including several in developing countries, report
that the sensitivity and specificity of these optimized tests lie in the
range of 95–100% and 98–100%, respectively
 High cost
CLINICAL FEATURES OF HIV INFECTION
The Disease Progression

Rapid viral High level of viral RNA

replication

Chronic
Acute Primary
HIV infection asymptomatic HIV Disease AIDS
HIV Infection
HIV Infection

• Window
Virus latency
period
• Seroconve
rsion
1-3 weeks 6-12 weeks 5-15 years
Syndrome
Primary HIV Infection

 Window period of virus is 7-21 days

 Fusion with CD4 cells occurs rapidly
 Virus migrates to regional lymph nodes, and enters the circulation
 HIV multiplies in the mucosa and draining lymphoreticular tissues
 Widespread dissemination to the brain and lymphatic system
 Signs and symptoms resembling of the mild mononucleosis-type illness
 Fever, fatigue, maculopapular rash, headache, lymphadenopathy,
pharyngitis, myalgia, arthralgia, aseptic meningitis, retrorbital pain,
weight loss, depression, GI distress, night sweats, oral/genital ulcers
Primary HIV Infection

 Acute illness may last from few days to more than 10 weeks
 Severe and prolonged symptoms are correlated with rapid diseases
progression
 Antibody responses can be detected in a few weeks, and Tc cells are
formed  decrease in viral load
 Within 6-12 weeks, antibodies to HIV are detectable in the blood, and
ELISA and Western Blot testing can document seroconversion
(seroconversion syndrome)  at this time, the patients are confirmed
as HIV+
 The duration of this stage is dependent on a number of factors
including the viral phenotype, host immune response and use of
antiretroviral therapy
Chronic Asymptomatic HIV Infection

 The acute infection and rapid, widespread viral dissemination is followed

by a chronic asymptomatic stage
 Viral replication is reduced (latent) in line with the immune response,
and the individual usually remains well
 There is a massive viraemia with wide dissemination of HIV in the blood
to lymphoid organs, but the resulting immune response only partially
suppresses HIV
 Gradual loss of CD4+ T cells and progressive deterioration of immune
function.
 There may be persistent generalized lymphadenopathy (PGL)
HIV Disease (Chronic Symptomatic HIV Infection)

 Manifests as the CD4+ T cell count progressively declines over a period

which may extend over 5-15 years or more
 The patient starts to manifest:
 Infections (P. carinii pneumonia, candidosis, cryptococcis,
herpesvirus, parasites, and MDR-TB)
 Neoplasms (Kaposi sarcoma – KSHV, lymphomas – EBV, cervical or
anal carcinomas – HPV)
 Neuropsychiatric disease (dementia and other cerebral syndromes:
loss of coordination, mood swings, etc.)
 General deterioration (anorexia, diarrhea, premature aging,
thrombocytopenia, etc.)
AIDS

 Term used when CD4+ T-lymphocyte count falls <200 cells/mL

 CDC classification based on clinical categories and laboratories
categories
Category A (HIV Infection)

 Asymptomatic HIV infection

 PGL
 Acute HIV infection with accompanying illness or history of acute HIV
Infection
Category B (HIV Disease)

 Bacillary angiomatosis (epithelioid  Idiopathic thrombocytopenia

angiomatosis) purpura
 Candidosis, oropharyngeal  Listeriosis
(thrush)
 Pelvic inflammatory disease
 Candidosis, vulvovaginal
 Peripheral neuropathy
 Cervical dysplasia
 Constitutional symptoms, such as
fever (38.5C) or diarrhea
 Hairy leukoplakia, oral
 Herpes zoster (shingles)
Category C (AIDS)

 Candidosis, bronchi, trachea, or  Encephalopathy, HIV-related

lungs
 Herpes simplex: chronic ulcer(s); or
 Candidosis, oesophageal bronchitis, pneumonitis, or
esophagitis
 Cervical cancer, invasive
 Histoplasmosis, disseminated or
 Coccidioidomycosis, disseminated extrapulmonary
or extrapulmonary
 Isosporiasis, chronic intestinal
 Cryptococcosis, extrapulmonary
 Kaposi sarcoma
 Cryptosporidiosis, chronic
intestinal  Lymphoma, Burkitt
 CMV disease
 CMV retinitis
Category C (AIDS) (cont.)

 Lymphoma, immunoblastic  Pneumocystis carinii (now jiroveci

) pneumonia (PCP)
 Lymphoma, primary, of brain
 Pneumonia, recurrent
 Mycobacterium avium complex or
M. kansasii, disseminated or  Progressive multifocal
extrapulmonary leukoencephalopathy
 Mycobacterium tuberculosis , any  Salmonella septicemia , recurrent
site (pulmonary or
extrapulmonary)  toxoplasmosis of brain

 Mycobacterium, other species,  Wasting syndrome due to HIV

disseminated or extrapulmonary (‘slim disease’).
ORAL LESIONS IN HIV INFECTION
Oral Lesions in HIV Infection

 Oral lesions are often clearly visible and several can be diagnosed
accurately on clinical features alone
 Certain oral lesions provide a strong indication of the presence of HIV
infection  useful markers of disease progression and
immunosuppression
 Thus oropharyngeal lesions feature in all classifications, staging, and
prognosis (CDC, 1993)
 Oral lesions have also been advocated and are used as entry criteria and
end points for prophylaxis therapy and vaccine trials.
Oral Candidosis

 Is the most common intraoral opportunistic fungal infection strongly

associated with HIV infection
 It is reported that oral/esophageal candidiasis, in HIV infected patients,
may herald the development of full-blown AIDS within 2 years
 The 4 clinical patterns seen are:
 Pseudomembranous candidiasis
 Erythematous candidiasis
 Hyperplastic candidiasis
 Angular cheilitis
 Treated with topical and/or systemic antifungals (depends on
severity)
Cryptococcosis

 Cryptococcus neoformans (yeast in both human and soils)  pigeon

feces and soil
 May disseminate from lungs to meninges, heart, spleen, pancreas,
adrenals, ovaries, muscles, bones, liver, and GI tract
 Most patients with disseminated cryptococcosis have
meningoencephalitis if untreated the fatality is over 70%
 Most common systemic mycoses in AIDS
 Diagnosis: microscopy, culture, and assay of serum or CSF for capsular
antigen or antibody
 Treatment: systemic/orally amphotericin B + flucytosine, followed with
itraconazole
Cryptococcosis

Skin Lesions Oral Lesions

 Oftenly involved the head and  Relatively are
neck
 Crater-like, nonhealing ulcers
 Erythematous papules or pustules
that my ulcerate, discharging pus-  Tender on palpation or friable
like material rich in cryptococcal papillary erythematous plaques
organisms  May disseminate to salivary gland
Cryptococcosis
Histopathology Features

 Necrotizing granulomatous inflammatory response

 Inflammatory infiltrate
 Epitheloid cells (macrophages)
 Multinucleated giant cells
 Central necrosis
 Yeast surrounded by a clear halo that represents the capsule
 Mucicarmine stain uniquely demonstrates its mucopolysaccharide
capsule
Histoplasmosis (Darling’s Disease)

 Histoplasma capsulatum
○ Dimorphic saprophytic fungus → yeast (human), mold (nature)
○ Soil contaminated with bird or bat feces
 The most common systemic mycoses in HIV/AIDS that manifests
oral lesions
 Includes acute, chronic, and disseminated pulmonary and cutaneous
forms
 May affect reticuloendothelial system, lungs, kidneys, and GI tract
 Oral Predilection : tongue, palate, and buccal mucosa; may also
appear at gingiva and lips
 Diagnosis : microscopy, culture, and serology test
Histoplasmosis

• 33% cases had oral

lesions
• Nodular/ulcerative
• Ulcerative lesion
usually covered by a
nonspecific gray
membrane
• Indurated
• Raised and rolled
border (~carcinoma)
Histoplasmosis

• Ulcerated granular lesion (A) and chronic ulceration (B) of

Histoplasmosis are easily mistaken clinically for carcinoma.
• Biopsy established the diagnosis.

A B
Histoplasmosis

• Scattered epithelioid
macrophages admixed
with lymphocytes and
plasma cells
• Some macrophages
contain organisms of
Histoplasma
capsulatum (arrows)
Antifungal Medication
Antifungal Medication
Periodontal Lesions of HIV (ECClearinghouse, 1993)

 Three atypical patterns of periodontal disease are associated strongly

with HIV infection:
 Linear gingival erythema (LGE)
 NUP (necrotizing ulcerative periodontitis)
 NUG (necrotizing ulcerative gingivitis)
 NS (necrotizing stomatitis) occurred when gingival necrosis extends
away from the alveolar ridges and creates massive areas of tissue
destruction
 Treatment : debridement, povidone-iodine irrigation, chlorhexidine
mouth rinse, and/or antifungal medication
Necrotizing Ulcerative Gingivitis
Necrotizing Stomatitis
Herpes Simplex Virus Infection

 Recurrent herpetic lesions may be widespread, occur in an atypical

pattern, and persist for months
 Herpes labialis may extend to the facial skin and exhibit extensive lateral
spread
 The persistence of active sites of HSV infection for >1 month  AIDS
 Treatment: antiviral therapy (oral acyclovir)
HIV-associated Recurrent Herpetic Infection
Varicella-Zoster Virus

 Recurrent HZV infection is more severe, with increased morbidity and

mortality rates
 In AIDS patients herpes zoster begins as a unilateral cluster of vesicles
and ulcers in a classical dermatome distribution but subsequently
extends beyond the dermatomal boundary and heals by scarring
 Treatment: oral acyclovir
 Routine zoster vaccination is not recommended; however, according
to some experts, this may be considered for those with controlled
HIV (CD4+ cells counts >200/mL)
Human Papillomavirus

 Most HPV lesions arise in anogenital region, although oral involvement

also is possible
 Benign oral lesion caused by HPV (oral warts)
 Oral squamous papilloma
 Verruca vulgaris
 Condyloma acuminatum
 Multifocal epithelial hyperplasia
 Prevalence is 1-4% greater than immunocompetent individuals
 Unusual HPV types (HPV-7, HPV-13, HPV-32) frequently are identified in
oral HPV lesions arising in HIV-infected patients
Human Papillomavirus

 HPV lesions may increased in frequency since the introduction of cART

(reason still unclear)
 Oral Predilection: labial mucosa, tongue, buccal mucosa, and gingiva
 Clinical features: multiple, white, spike-like projections, pink verrucous
growths, or slightly elevated sessile papules
 Histopathology features: hyperplastic or acanthotic stratified
squamous epithelium, koilocytosis (vacuolization of numerous
epithelial cells), and dysplasia may occur
 Treatment: surgical excision, cryosurgery, cidofovir, intralesional or
systemic INF-α, oral cimetidine, and topical podophyllin
Human Papillomavirus
Human Papillomavirus
Oral Hairy Leukoplakia (OHL)

 Hairy leukoplakia  corrugated surface of the epithelium

 Associated with Epstein-Barr virus (EBV)
 Immunohistochemistry
 Electron microscopy
 In situ hybridization
 PCR
 It has been hypothesized that basal epithelial cells of the lateral margin
of the tongue normally harbor latent EBV
 Significant diminution of Langerhans cells by HIV, in the affected site,
permits reactivation of EBV with subsequent epithelial hyperplasia
OHL Clinical Features

 Bilateral white mucosal plaque which range in appearance from faint,

white vertical streaks to thickened, furrowed areas of leukoplakia with a
shaggy surface (does not rub off)
 Usually asymptomatic, some may have occasional slight soreness and
discomfort
 Predilection: lateral border of the tongue
 Infrequently may extend to cover the entire dorsal and lateral surfaces
of the tongue
 Rarely, the buccal mucosa, soft palate, pharynx, or esophagus may be
involved
OHL
OHL Histopathology Features

 Hyperparakeratosis with surface corrugations or thin projections

 Ballon cells  acanthotic epithelium with a bandlike zone of lightly
stained cells with abundant cytoplasm
 Nuclear beading of superficial epithelial cells  peripheral margination
of chromatin, caused by extensive EBV replication that displaces the
chromatin to the nuclear margin
 No dysplasia noted
 Heavy candida infestation may of the parakeratin layer without
inflammatory reaction may be seen
Oral Hairy Leukoplakia
OHL Treatment

 Antifungals (many OHL cases reveals candida):

 Topical  nystatin and clotrimazole
 Systemic  ketoconazole and fluconazole
 Antivirals agents:
 Acyclovir, decyclovir, ganciclovir
 Discontinuation of therapy results in recurrence of the lesion due to
immunosuppressed condition
 Surgical excision or cryotherapy also has been used by some
Kaposi’s Sarcoma

 Is a multifocal neoplasm of vascular endothelial origin

 Associated with HHV-8 (KSHV)
 Predilection: palate, gingiva, tongue and oropharynx or the skin
 Clinical appearance: macular, nodular, or raised and ulcerated, color
varies from red to purple
 Early lesions : flat, red, asymptomatic
 Progressed lesions: darkened, symptomatic due to trauma or
infection
 Treatment: intralesional vinblastine or surgical excision; systemic
chemotherapy for widespread or disseminated form
Kaposi’s Sarcoma
Kaposi’s Sarcoma
Aphthous Ulcers

 Present as recurrent, round, shallow, painful ulcers of variable size and

duration that are typically found on nonkeratinized oral mucosa
 Oral ulcers in HIV-infected patients are large and more extensive
 They usually measure more than 2 cm in diameter with regular borders
 Treatment: topical steroids, chlorhexidine and tetracycline rinses
Aphthous Ulcers in HIV Infected Patient
Oral Squamous Cell Carcinoma (OSCC)

 OSCC has been reported in HIV/AIDS patients with the same frequency
as in the general population, associated with same risk factors but at a
younger age
 Impaired immunosurveillance, and an increased chance of HPV infection
are a few suggested causes
 Treatment: surgical resection, chemotherapy and/or radiotherapy
HIV-associated OSCC
HIV-associated Salivary Gland Disease

 5% of HIV patients exhibit this condition (greater prevalence among

children)
 Considered as diffuse infiltrative lymphocytosis syndrome (DILS)
 Bilateral parotid enlargement associated with cervical lymphadenopathy
 Qualitative and quantitative xerostomia, caused by:
 Drugs (antiretroviral, antifungals, chemotherapeutics, etc.)
 Oral diseases (candidiasis, etc.)
 Treatment: oral prednisone and antiretroviral therapy, some undergo
parotidectomy or radiation therapy
Persistent Generalized Lymphoma (PGL)

 After seroconversion, HIV disease often remains silent except for PGL
 The prevalence of this early clinical sign approaches 70%
 Consists of lymphadenopathy that has been present for >3 months and
involves two or more extrainguinal sites
 Predilection: posterior and anterior cervical, submandibular, occipital,
and axillary nodes
 Nodal enlargement fluctuates, with dia: 0.5 - 5.0 cm (usually >1 cm)
 Almost one-third of affected and untreated patients will have diagnostic
features of AIDS within 5 years
Persistent Generalized Lymphoma (PGL)
Non-Hodgkin’s Lymphoma

 HIV patients are 60 times at risk of non-Hodgkin’s lymphoma than the

general population
 3% of HIV-infected people develop lymphomas
 A relationship between Epstein-Barr virus infection and non-Hodgkin’s
lymphoma has been suggested
 This lesion tends to present as a large, painful, ulcerated mass on the
palate or gingival tissues
 Diagnosis: biopsy with a confirmatory immunohistochemical panel of
markers
 Treatment: combination of chemotherapy and radiation conjuction
with cART
Non-Hodgkin’s Lymphoma
TREATMENT AND PROGNOSIS
Treatment and Prognosis

 Aim : arrest and reverse the damage to the immune system

 The introduction of cART has resulted in dramatically reduced morbidity
and mortality
 Although numerous combinations are possible, cART often consists of:
 2 nucleoside reverse transcriptase inhibitors (NRTI), combined with
 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), boosted
protease inhibitor (PI), or integrase inhibitor (II)
 Viremia typically declines to undetectable levels, and there is significant
immune reconstruction
Treatment and Prognosis

 Although cART works well for most patients, downsides of such therapy
include cost, toxicity, adverse reactions, and difficulty with
compliance
 Immune reconstitution syndrome (IRIS) occurs on some patients who
receive antiretroviral therapy during advanced stages of disease
 Hyper-inflammatory response to pathogens and pathogenic
antigens due to immune reconstitution long-term cART
 Increased risk for premature cardiovascular disease, liver disease,
kidney disease, and both HIV-related and non-HIV-related cancers
 cART alone is unable to cure HIV infection
 Persistence of viral reservoirs in the peripheral blood and lymphoid
tissues
IRIS (Immune Reconstitution Syndrome)

 A paradoxical worsening or recurrence of opportunistic infections and

symptoms
 Affects 8% to over 30% of HIV/AIDS patients, and also may affect
immunosuppressed individuals
 Appears to be linked to higher CD8 cell counts induced by ART
 Increased activity of IL-2 and IL-12 may contribute
 AIDS patients are more at risk if they are put on ART for the first time, or
if they have recently been treated for an opportunistic infection
 Treatment: antimicrobials and corticosteroids
IRIS (Immune Reconstitution Syndrome)
Treatment and Prognosis

 Treatment of AIDS involves prophylaxis and treatment of opportunist

infections as well as using antiretrovirals
 Depending on the CD4 count, prophylaxis is given for specific
opportunistic infections such as Pneumocystis jirovecii and
Cryptococcus neoformans
 When opportunist infections are diagnosed, they are treated
appropriately
 Co-trimoxazole or pentamidine with or without steroids  P.
jirovecii
 Ganciclovir  CMV
 Fluconazole or amphotericin  C. Neoformans
 Be cautious of drugs interactions!
Monitoring Progress

 The CD4 count and the plasma viral load should be assayed when
therapy is started and at 1-month and 3-4 month intervals thereafter
 If there is a response, the RNA load will decrease within a few days, will
drop by 1 log10 at 2-8 weeks and be less than 40 copies/mL by 4-6
months
 If these objectives are not achieved, a new combination regimen should
be started (assuming patient compliance with the prescribed regimen)
 The resistance pattern of the patient’s virus should be tested before
selecting new drugs
HIV PrEP (Pre-exposure Prophylaxis)

 Daily oral tenofovir disoproxil fumarate 300 mg (TDF) / emtricitabine

200 mg (FTC)  dose dependent efficacy
 Daily oral TDF/FTC use has been shown to be safe in reducing the risk
for sexual HIV acquisition when used consistently
 Considerations using PrEP by CDC:
 Contraindicated for PrEP in persons with unknown or HIV+ status
 Can be safe and effective in reducing HIV infection from penile-
vaginal sex
 Help protect HIV- partners in discordant couples during attempts to
conceive
 Before beginning PrEP and if not pregnant at initiation, women of
reproductive age should have a regular documented test while
receiving PrEP
DENTAL ASPECTS OF HIV/AIDS
Dental Aspects of HIV/AIDS

 Immunologically stable HIV+ patients on ART may be considered the

best dental treatment risk
 Those with neutropenia and/or CD4 T-lymphocyte count below 200/mL
require antibiotic cover before surgery or after maxillofacial injuries
 Drugs interaction (commonly PIs and NNRTIs) :
 LAs  LA↑, antiretroviral↓
 NSAIDs  excess bleeding, granulocytopenia
 Antifungals  cardiotoxicity, arrhythmias, disulfiram-like reactions,
haematological toxicity, antifungals↓
 Antibiotics  arrhythmias, antibiotics↑
 Corticosteroids  corticosteroids↑
Risk Factors of Postoperative Complications in
HIV/AIDS

 Low CD4+ count

 High viral load
 Low lymphocyte count
 Neutropenia
 Bleeding tendency (thrombocytopenia, liver damage, etc.)
 Another concomitant infection
Transmission of HIV to or from Health-care
Professionals

 Accidental exposure to blood following a needlestick (sharps)

 The highest reported risks are after a needlestick incident, especially
with:
 Devices that are visibly contaminated with blood
 Hollow-bore needles that have been in an artery or vein
 Deep injuries
 Exposure to blood from patients with terminal infection
Transmission of HIV to or from Health-care
Professionals

 Needlestick injuries are most likely in the following situations:

 During needle recapping
 During surgery, especially wound closure
 When an uncapped needle has ended up in linen, etc.
 When taking an unsheathed used needle to the sharps container
 During the cleaning and transporting of waste material
 When using more complex collection and injection techniques
 In accident and emergency departments
 In high-stress interventions
Controlling HIV in Health Setting

 Heat, in autoclave or hot-air oven

 Glutaraldehyde 2%
 Hypochlorite (10.000ppm); 1 in 10 dilution of domestic bleach
 Other disinfectants, including alcohols
 Sterile gloves, renew during intercourse
THANK YOU

Dewi Agustini – 040001600033

Faculty of Dentistry
Trisakti University