HIV

HIV and Periodontium

ContentsIntroductionEpidemiologyPathogenesis ClassificationHIV testingOral manifestations of HIV infectionPathogenesis of HIV associated periodontal diseasesGingival and periodontal diseasesPeriodontal treatment protocolConclusionReferences

Introduction

AIDS

Montagnier et al 1984: lymphadenopathy-associated virus (LAV)

Gallo et al. 1984: human T-cell leukemia/lymphoma virus (HTLV-III)

Dr. Suniti Solmon

Introduction

Epidemiology

UNAIDS, 2004

5th leading cause of death

75% reside in Sub-Saharan Africa, and South east Asia (Piot et al 2001)

Epidemiology

World's third-largest population suffering from HIV

In 2007, AIDS prevalence rate 0.30%—89th highest in the world.

2008 20092.2

2.25

2.3

2.35

2.4

Population (in million) living with HIV

Population (in million) living with HIV

Pathogenesis

Helper T cells, monocytes, macrophages, Langerhans cells, and some neuronal and glial brain cells

R5 virus – macrophages - predominate during the early stages

X4 virus - later stage of infection - associated with increased cytopathogenicity

and more rapid T-cell depletion (Connor et al 1993)

Pathogenesis of HIV

Pathogenesis of HIV

109 CD4 cells destroyed daily and replacement of only 6–7% of the total CD4 cells each day (Ho et al 1995).

Release of virus and infected T

cells into the blood

CD4 depletion: Cytotoxic T-cell

immune cytolysis.

Continuous replication of virus occurs in the lymph

nodes

Weeks to months after initial exposure acute symptoms

Acute phase (up to 2 weeks)

Antigenic viremia - extended period of time before seroconversion occurs

HIV AIDS (12 years or more)

Pathogenesis of HIV

B cell not infected

↑ risk for malignancy and infections with microorganisms such as viruses, mycobacterioses, and mycoses.

↑ risk for adverse drug reactions

Traumatic injury Oral transmucosal viral transmission allowing infection of circulating host defense cells.

Pathogenesis of HIV

Classification and staging

Centers for Disease Control,1982

Severe immunodeficiency (CD4 count of < 200/mm3 or a T4 lymphocyte of < 14% of total lymphocytes)

Classification and stagingCDC Surveillance Case Classification

Category A: Acute symptoms or asymptomatic diseases, along with individuals with PGL, with or without malaise, fatigue, or low-grade fever.

Category B: Symptomatic conditions such as candidiasis; herpes zoster; OHL ; idiopathic thrombocytopenia; or constitutional symptoms of fever, diarrhea, and weight loss.

Category C: With outright AIDS as manifested by life-threatening conditions identified by CD4+ T lymphocyte levels of less than 200 per cubic millimeter

Tests for HIV

Immunological tests

•Total lymphocyte count < 2,000/cumm•CD4 < 200/cumm•Thrombocytopenia•Raised IgG and IgA

Specific tests

•Antigen detection : p24 antigen•Virus isolation•Antibody detection

Oral manifestationsMealey et al 1996

• Oral candidiasis

• Oral hairy leukoplakia

• Atypical periodontal diseases

• Oral Kaposi's sarcoma

• Oral non-Hodgkin's lymphoma

• Melanotic hyperpigmentation

• Mycobacterial infections

• Necrotizing ulcerative stomatitis

• Miscellaneous oral ulcerations

• Viral infections

• Viral infections (e.g., cytomegalovirus, molluscum contagiosum)

• Recurrent aphthous stomatitis

• Bacillary angiomatosis

Oral manifestations

Oral candidiasisMost common oral lesion in HIV diseases (90% of patients)

Diminished host resistance

85% to 95% are associated with Candida albicans

Oral candidiasis ↑ - CD4+ lymphocytes ↓ 200 cells/mm3 (Katz et al 1992)

Lamster et al (1994): 16% - homosexuals 46% - injected drug users

Oral manifestations

Pseudomembranous candidasis (thrush)

Erythematous candidasis

Angular chelitisHyperplastic candidiasis

DiagnosisOral candidiasis + esophageal candidiasis, a diagnostic sign of AIDS (Tavitian et al 1986)

Oral manifestations

TreatmentOften refractory or recurrent

10% of candidial organisms - resistant to long-term fluconazole therapy and cross-resistance to itraconazole, amphotericin B oral suspension and IV amphotericin B

More common when low CD4 counts

HAART - significant decrease in incidence of oropharyngeal candidiasis and has reduced the rate of fluconazole resistance.

Oral manifestations

Topical antifungal agents

Systemic antifungal agents - ketoconazole, fluconazole, itraconazole, and amphotericin B

Oral manifestations

Oral hairy leukoplakiaDescribed in the early 1980s and primarily occurs in persons with HIV infection

Other areas: Dorsum of the tongue, buccal mucosa, floor of the mouth, retromolar area, and soft palate

Oral manifestations

Human papilloma virus, but subsequent evidence suggests Epstein Barr virus

Candida organisms - secondary invaders and not the cause

The microscopic confirmation - strong indicator that the patient will develop AIDS

83% of HIV-infected patients with OHL develop AIDS within 31 months, 100% of patients with OHL eventually developed AIDS. (Greenspan et al 1989)

Oral manifestations

Differential diagnosis• Carcinoma• Frictional and idiopathic keratosis• Lichen planus • Tobacco-related leukoplakia• Psoriasiform lesions• Hyperplastic candidiasis

Oral manifestations

Treatment• Anti-viral drugs like acyclovir, valcyclovir• Laser or conventional surgery• Lesions tend to re-appear once the therapy is

discontinued (Maeley et al 2004)

Oral manifestations

Kaposis sarcomaRare, multifocal, vascular malignant neoplasm

Described in 1872 - skin of the lower extremitiesof older men of Mediterranean origin

Most common in homosexual or bisexual men

Male-to-female ratio is 20:1

Oral manifestations

HIV-infected individuals are 7000-fold more likely to develop KS (Fleming et al 1998)

Epidemiologic forms• Classic• African• Organ transplant-associated• AIDS-associated

Classic form - localized and slowly growing lesion AIDS-associated- much more aggressive lesion

- 71% show oral lesions

Oral manifestations

HHV-8 Found in the saliva of patients with high CD4 cell

counts

Oral cavity - first or only site of the lesions (60%)

Oral manifestations

Gingival involvement may result in alveolar bone destruction and loss of teeth (Reichert et al 2003)

Differential diagnosis • Hemangioma• Hematoma• Pyogenic granuloma • Atypical hyperpigmentation• Sarcoidosis• Bacillary angiomatosis• Angiosarcoma• Pigmented nevi

Oral manifestations

Treatment• No curative treatment• Laser excision, cryotherapy, radiation therapy,

intralesional injection with vinblastin, interferon-alpha, sclerosing agents(3% sodium tetradecyl sulfate) or chemotherapeutic agents

• Nichols et al described the intralesional injection of vinblastin at a dose of 0.1mg/cm2 using a 0.2 mg/ml solution in saline

• Median survival time after onset of KS ranged from 7 to 31 months (Chun et al 1995)

Oral manifestations

Bacillary angiomatosisAn infectious vascular proliferative disease

Rickettsia-like organisms, Bartonellaceae, Rochalimaea quintana or others

Gingival BA - red, purple, or blue edematous soft tissue lesions destruction of periodontal ligament and bone

More prevalent with low CD4 levels

Treatment - doxycycline or erythromycin +conservative periodontal therapy and possibly excision

Oral manifestations

Oral pigmentation↑ incidence of oral hyperpigmentation in HIV-infected individuals (Kumar et al 2003)

Etiology• Related to prolonged use of drugs such as

zidovudine, ketoconazole or clofazimine • Zidovudine - excessive pigmentation

of skin and nails• Pneumocystis carinii infection or

cytomegalovirus or other viral infections

Oral manifestations

Atypical ulcersHigher incidence of recurrent herpetic lesions and aphthous stomatitis

Herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus

Herpes may involve all mucosal surfaces and extend to the skin and may persist for months

Neutropenic patients

Oral manifestations

Acyclovir (200-800 mg administered five times daily for at least 10 days) followed by maintenance therapy (200 mg 2-5 times a day)

Recurrent aphthous stomatitis - topical or intralesional corticosteroids, antimicrobial mouth rinses, oral tetracycline rinses

Oral manifestations

Recurrent apthous stomatitis Recurrent herpetic lesions

Pathogenesis of HIV associated periodontal

diseasesRole of microbes

Harbour both unusual oral organisms(virus and fungi) and typical periodontopathogens

Murray et al. (1988) - Candida albicans

Candida invasion associated with severity of periodontal diseases in HIV patients. (Odden et al 1995)

Suppression of the protective arm and stimulation of the destructive arm of host response

HIV virus - suppresses T-helper cells and/or by acting as a “superantigen” which may provoke an unregulated and destructive host response (Shirai et al 1992)

Other viruses

Contreras et al 2001

Overgrowth of periodontal pathogens and opportunistic infections; ↑ secretion of inflammatory mediators (Slots et al 2000)

↑ incidence of necrotizing forms of periodontal diseases.

Pathogenesis of HIV associated periodontal diseases

Murray et al 1989


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102030405060708090

HIV associated gingivitisHIV associated periodontitis

Role of hostGreenspan et al 1990

• HIV associated gingivitis : 0.9 to 1.7• HIV associated periodontits: 0.1 to 0.9

Immune function regulation

Effect on neutrophils

Lynch et al 1991 – IL-1β


Polyclonal activation of B cellsHyperresponsive phagocytosisDefective chemotaxis of monocytes and neutrophils

Lymphokine productionNatural killer cell activityResponse to soluble antigenImmunoglobulin production

Gingival and periodontal diseases

Linear gingival erythemaClassified as a gingival disease of fungal origin

Precursor to the necrotizing ulcerative periodontal diseases

Patton et al 2003

LGE - positive predictive value of 70% NUP - positive predictive value of 50%

Histologic evaluation revealed ↑ polymorphonuclear leukocytes and IgG-producing plasma cells

Treatment• Follow meticulous oral hygiene procedures. • If the lesions do not subside after 2-3 weeks, then

systemic antifungal medication (Flucanazole for 7-10 days)

• 2-3 month recall maintenance


Necrotizing ulcerative gingivitisUlceration of the interdental papilla with gingival bleeding and severe pain

Punched out appearance of the interproximal papilla

Affected area typically covered with a fibrinous pseudomembrane


Treatment• Cleaning and debridement of affected sites with

peroxide and topical anesthetic

• Avoid tobacco, alcohol and condiments

• Systemic antibiotics such as metronidazole or amoxicillin


Necrotizing ulcerative periodontitisAn extension of NUG in which bone loss and periodontal attachment loss occurs

Candidial organisms and human herpes virus (Slots et al 2004)

Spirochetes, zones of aggregated polymorphonuclear leukocytes, and necrotic cells found in NUG and NUP (Cobb et al 2003)



NUP

Soft tissue necrosis, Rapid periodontal

destruction

Bone is often exposed, resulting

in necrosis

Sequestration

NUG

Riley et al 1992 85 - periodontally healthy 59 - gingivitis 54 - mild, moderate, or advanced periodontitis none had NUG; and 2 - NUP

NUP in only 6.3% patients out of 700 HIV-positive individuals (Glick et al 1994)

Patients with <200CD4 cells are 20.8 times more likely to have NUP (Rams et al 1991)


Treatment• Meticulous oral hygiene procedures• In severe cases, antimicrobial therapy

(metronidazole 250mg, two tablets taken immediately followed by one tablet QID for 5-7 days)


Necrotizing ulcerative stomatitis Extension into the adjacent bone osteonecrosis and sequestration (similar to noma)

May occur separately or as an extension of NUP

Treatment • Antibiotics (metronidazole)• CHX mouthrinses• If osseous necrosis has occurred then removal of

affected bone


Chronic periodontitisMaeley et al 2004, Barr et al 1992

Lamster et al 1994

Robinson et al 2000

Maticic et al 2000

Drinkard et al

Aichelmann-Reidy et al 2010

Treatment


Periodontal treatment protocolHealth status

Health history, physical evaluation, and consultation with physician• What is the CD4+ T4 lymphocyte level? • What is the current viral load? • How do current CD4+ T4 cell and viral load counts differ from

previous evaluations? • How often are such tests performed? • How long ago was the HIV infection identified? • Is it possible to identify the approximate date of original exposure? • Is there a history of drug abuse, sexually transmitted diseases,

multiple infections, or other factors that might alter immune response?

• What medications is the patient taking? Does the patient describe or present with possible adverse side effects from medications being taken?

Infection control measuresRisk for acquiring as well as transmitting infections

Universal precautions

Sterilisation

Periodontal treatment protocol

Goals of TherapyRestoration and maintenance of oral health, comfort, and function

Conservative, nonsurgical periodontal therapy

Performance of elective surgical periodontal procedures

Thrombocytopenia


Maintenance TherapyPrevent relapse after successful treatment of an acute opportunistic infection

Recall visits

Blood and other medical laboratory tests


Psychologic factorsHIV infection of neuronal cells

Patients confidentiality


Conclusion

A chronic progressive process with a variable period of clinical latency but no microbial latency. Knowledge of the pathogenesis and the natural history of progression is valuable in diagnosis as well as management

ReferencesMark Ryder. An update on HIV and periodontal disease. J Periodontol 2002; 73: 1071-1078

Shilpa Kolhatkar, Syed Khalid, Anne Rolecki, Monish Bhola, and James R. Winkler Immediate Dental Implant Placement in HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy: A Report of Two Cases and a Review of the Literature of Implants Placed in HIV-Positive Individuals. J Periodontol 2011;82:505-511.

Patriciaa Murray Periodontal diseases in patients infected by human immunodeficiency virus. Periodontology 2000 1994; Vol. 6: 50-67

References

Michael T. Yin, Jay F. Dobkin & John T. Grbic. Epidemiology, pathogenesis, and management of human immunodeficiency virus infection in patients with periodontal disease. Periodontology 2000 2007; Vol. 44: 55–81

Mary E. Aichelmann-Reidy, Dena L. Wrigley, and John C. Gunsolley HIV Infection and Bone Loss Due to Periodontal Disease. J Periodontol 2010;81:877-884.

Lauren L. Patton, Daniel A. Shugars, Arthur J. Bonito. A systematic review of complication risks for HIV-positive patients undergoing invasive dental procedures. J Am Dent Assoc, Vol 133, No 2, 195-203

References

Walter Hall. 3rd edition. Decision making in Periodontology. Mosby

Ananthnarayan R, Jayaram Paniker. 5th edition. Textbook of microbiology. Orient Longman

Newman, Takei, Klokkevold, Carranza. 10th edition. Carranza’s Clinical Periodontology. W. B. Saunders Company.

……Thank you

HIV

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