Oral Manifestations


Oral Manifestations of HIV/AIDS in the HAART Era


Oral Manifestations of HIV/AIDS in the HAART Era
David A. Reznik, D.D.S.                 Christine O’Daniels, RN-BC

Oral manifestations of HIV infection are a fundamental component of disease progression and occur in approximately 30 to 80 percent of the affected patient population. 1, 2, 3 Factors which predispose expression of oral lesions include CD4 counts less than 200 cells/mm3, viral load greater than 3000 copies/mL, xerostomia, poor oral hygiene and smoking. 4,5 Oral lesions are differentiated as fungal, viral and bacterial infections, neoplasms such as Kaposi’s sarcoma and non-specific presentations such as aphthous ulcerations and salivary gland disease.

Overall prevalence of the oral manifestations of HIV disease has changed since the advent of highly active antiretroviral therapy (HAART). One study noted a reduction of oral lesions from 47.6% pre-HAART to 37.5% during the HAART era 3. The details of this study included a significant reduction in oral hairy leukoplakia and necrotizing ulcerative periodontitis, yet there was no significant change in the incidence of oral candidiasis, oral ulcers and Kaposi’s sarcoma. This population did, however, see an increase in salivary gland disease. Other published reports show a markedly increased incidence of oral warts in the HAART era. 6,7

Treatment of the oral diseases seen in association with HIV disease is reportedly very low. A study of 1424 adults who participated in the AIDS Cost and Utilization Study revealed that only 9.1% reported treatment for oral manifestations.  After adjusting for CD4 count and other variables, African-Americans and Hispanics were significantly less likely to receive treatment. Factors which were significant in regards to receiving care for oral disease included more than a high school education, participation in clinical trials and utilization of counseling services.8 The ability to differentiate one manifestation from another, and to manage some of the more common conditions are fundamental to the overall health care of this patient population. The following discussion will cover the most commonly seen oral manifestations seen in association with HIV infection.

Fungal Infections:

The most common fungal infection seen in association with HIV infection is oropharyngeal candidiasis. There are three frequently observed forms of oral candidiasis: erythematous candidiasis, pseudomembranous candidiasis and angular cheilitis. Erythematous candidiasis (EC) presents as a red, flat, subtle lesion either on the dorsal surface of the tongue and/or the hard/soft palates. EC tends to be symptomatic with patients complaining of oral burning, most frequently while eating salty or spicy foods or drinking acidic beverages. Clinical diagnosis is based on appearance, taking into consideration the person’s medical history and virologic status. The presence of fungal hyphae or blastospores can be confirmed by performing a potassium hydroxide preparation. Although EC has been identified as one of the more common oral manifestations seen in association with HIV disease, this presentation is frequently under-diagnosed. 4 Due to the limited nature of this infection, treatment involves the use of topical antifungal therapies.

Pseudomembranous candidiasis (PC) appears as creamy white curd-like plaques on the buccal mucosa, tongue and other oral mucosal surfaces that will wipe away, leaving a red or bleeding underlying surface. The most common organism involved with the presentation of candidiasis is Candida albicans, however there are increasing reports of the increased incidence of non-albicans species. 9 Like EC, diagnosis of PC is based on clinical appearance taking into consideration the person’s medical history. Potassium hydroxide preparation, fungal culture or biopsy, may be useful in obtaining an accurate diagnosis. There has been a decline in the occurrence of PC in patients who are on successful highly active retroviral regimens containing protease inhibitors. A review of the literature suggests that immune reconstruction alone does not account for this reduction, but rather the added effect of protease inhibitors on candidal virulence factors such as aspartyl protease.10 Whereas there has been a decline in the prevalence of PC in the HAART era, this is still one of the most common oral manifestations seen in HIV disease. Treatment should be based on the extent of the infection with topical therapies (nystatin, clotrimazole) utilized for mild to moderate cases and systemic therapies (fluconazole) used for moderate to severe presentations. Antifungal therapy should last for two weeks to reduce the colony forming units to the lowest level possible to prevent recurrence.

As HIV disease progresses and immunosuppression becomes more severe, the incidence and severity of oropharyngeal candidiasis increase. The introduction of oral azoles, most notably fluconazole, has led to the increased incidence of azole resistant Candida albicans as well as the emergence of non-albicans species such as Candida glabrata, which are inherently resistant to this class of drug.11 Factors that increase the probability of azole resistant strains of Candida presenting in the oral cavity include previous exposure to azoles, low CD4 count and the presence of non-albicans species.12, 13 To minimize the risk of resistance, topical therapies should be considered for first-line treatment of initial or recurrent cases of mild to moderate oropharyngeal candidiasis.11 Systemic therapies should be utilized for moderate to severe cases.

The clinical presentation of Angular cheilitis (AC) is erythema and/or fissuring of the corners of the mouth. AC can occur with or without the presence of EC or PC. Angular cheilitis can exist for an extensive period of time if left untreated. Treatment involves the use of a topical antifungal cream directly applied to the affected areas four times a day for the two-week treatment period.

Linear Gingival Erythema (LGE), a periodontal disease, presents as a red band along the gingival margin, which may or may not be accompanied by occasional bleeding and discomfort. LGE is seen most frequently in association with anterior teeth, but commonly extends to the posterior teeth. LGE can also present on attached and non-attached gingiva as petechia-like patches.  Research has indicated there may be a relationship between sub-gingival colonization of Candida species and HIV-related periodontal conditions including LGE.14 The most recent classification of periodontal diseases by the American Academy of Periodontology grouped LGE under “gingival disease of fungal origin”.15 Treatment for this condition would include debridement by a dental professional followed by twice daily rinses with a 0.12% chlorhexidine gluconate suspension for two weeks and improved oral hygiene home care.

Bacterial Diseases:

Whereas chronic adult periodontal disease occurs frequently in persons living with HIV disease, three unique presentations of periodontal disease have also been reported in this patient population: the previously discussed linear gingival erythema, necrotizing ulcerative gingivitis (NUG) and necrotizing ulcerative periodontitis (NUP). The demarcation between necrotizing gingivitis and necrotizing periodontitis was created to define the difference between the rapid destruction of soft (NUG) and hard (NUP) tissues. It has not been determined whether or not NUG and NUP are the same or unique entities and both have been classified as “Necrotizing Periodontal Diseases” by the American Academy of Periodontology. Due to the lack of significant differences in the microbial profile of these two conditions and similarity in treatment, this discussion will focus on NUP, which is a marker of severe immune suppression.16 This condition is characterized by severe pain, loosening of teeth, bleeding, fetid odor, ulcerated gingival papillae and rapid loss of bone and soft tissue. Patients often refer to their pain as “deep jaw pain.” Prompt referral to a dental professional for removal of dental plaque, calculus and necrotic soft tissues utilizing a 0.12% chlorhexidine gluconate or 10% povidone iodine lavage will alleviate symptoms. Patients should be placed on antibiotic therapy effective against gram-negative flora such as metronidazole or Augmentin.  The healthcare team should address pain management, nutritional supplementation and stress the importance of oral hygiene. Timely referral to the primary care team is indicated to rule out other systemic opportunistic infections.

Viral Diseases:

HSV-1 infection is widespread and oral manifestations of herpes lesions are common. Seventeen percent of the US population over age 12 experienced an oral herpetic lesion over a 1-year period.17 Recurrent intraoral herpes simplex starts as a small crop of vesicles that rupture to produce small, painful ulcerations which may coalesce. Although these herpetic ulcerations are often self-limiting, the use of an antiviral medication such as acyclovir is sometimes necessary to control the outbreak. Medications such as acyclovir stop viral replication and allow the affected area to heal.

Herpes Zoster, a reactivation of the varicella zoster virus, can occur along any branch of the trigeminal nerve; therefore an intraoral or extraoral presentation along branches of this nerve is possible. The external lesions will start as vesicles, break open and then crust over. The intraoral lesions will start as vesicles, burst and then present as oral ulcerations. Since both of these presentations are along the trigeminal nerve, the patient’s chief complaint may be toothache of unknown origin.  Treatment options include higher doses of acyclovir (800 mg, five times a day for 7 to 10 days) or famciclovir 500 mg three times a day for 7 days.).

Oral hairy leukoplakia (OHL) is caused by the Epstein-Barr virus and presents as a white corrugated, nonremovable lesion on the lateral borders of the tongue. Studies have shown a significant decrease in the incidence of OHL in the HAART era.3,4 This condition is normally asymptomatic and does not require therapy unless there are cosmetic concerns. Patients, who present with this condition while on HAART may be experiencing a failure in their present antiretroviral regimen.

Oral warts due to Human papillomavirus (HPV) have dramatically increased in the HAART era.6,7 One study noted the risk of oral warts was associated with a ³ one-log10 decrease in HIV RNA in the 6 months prior to oral HPV diagnosis, which suggests that this may in part be related to immune reconstitution.6 Oral warts may appear cauliflower-like, spike or raised with a flat surface. Treatment, which may involve surgery, laser surgery or cryotherapy, is problematic, as these lesions tend to recur.

Neoplastic Diseases:

Kaposi’s sarcoma (KS) is still the most frequent oral malignancy seen in association with HIV infection, although the incidence has dramatically decreased in the HAART era.4 For homosexual men with AIDS, incidence of all presentations of KS is highest in the 30 – 39 age group with 5 cases/100 person-years.18 Kaposi's sarcoma-associated herpesvirus (KSHV) has been implicated as a co-factor in the presentation of KS in persons living with HIV disease. The overall prevalence of KSHV in Texas blood donors proved to be 15%, which is higher than studies performed in other states.19

The clinical appearance of KS can be macular, nodular, or raised and ulcerated; the color can range from red to purple. Early lesions tend to be flat, red and asymptomatic, with the color becoming darker as the lesion ages. As lesions progress they can interfere with the normal functions of the oral cavity and become symptomatic secondary to trauma or infection. A biopsy is necessary for a definitive diagnosis. Treatment of oral lesions ranges from localized injections of chemotherapeutic agents, such as vinblastine sulfate, to surgical removal. For persons who present with extraoral and intraoral KS, systemic chemotherapy may be the treatment of choice. It is important that the entire primary health care team, including the primary care provider, dentist and oncologist work closely together in order to facilitate the best possible outcome. Oral hygiene should be stressed for people with oral KS.

Non-Hodgkin’s lymphoma is an AIDS defining condition that, on occasion, presents in the oral cavity. This lesion tends to present as a large, painful, ulcerated mass on the palate or gingival tissues. A biopsy is necessary for a definitive diagnosis. The oral health care team should refer patients with a diagnosis of non-Hodgkin’s lymphoma to an oncologist for treatment.


Salivary Gland Disease and xerostomia

Salivary gland disease is clinically apparent by an increase in the size of the major salivary glands, most notably the parotids. Biopsy of suspect enlarged parotid salivary glands has revealed an increase in lymphocytic infiltrates, more specifically, CD8 cells.

This condition usually presents as a bilateral enlargement of the parotid salivary glands and is often times accompanied by symptoms of dry mouth. There has been a reported increase in the presentation of salivary gland disease in the HAART era, which may be related to a reconstitution syndrome.3

Xerostomia or dry mouth is common complaint among people living with HIV disease. Approximately 29% of those participating in the HIV Cost and Utilization Study cohort reported symptoms of xerostomia. Factors which proved to be significant in the presentation of xerostomia included the previously referenced salivary gland disease, use of medications to manage HIV and other conditions, smoking, and a viral load of > 100,000/mm3. 20

Symptoms of dry mouth can be temporarily alleviated by sucking on sugar-free hard candies, chewing sugar-free gum and by using oral moisturizers. The change in the quantity and quality of saliva may lead to increased dental decay and therefore meticulous oral hygiene should be stressed and use of prescription topical fluoride preparations encouraged.

Recurrent Aphthous Ulcerations:

Recurrent aphthous ulcerations (RAU) are a common occurrence with approximately 17 percent of the U.S. population reporting an episode within a twelve-month period of time17. RAU present on non-keratinized or non-fixed tissues such as labial and buccal mucosa, the floor of the mouth, ventral surface of the tongue, posterior oropharynx and the maxillary and mandibular vestibules.  RAU are characterized by a halo of inflammation and a yellow-gray pseudomembranous covering. RAU, which last between 7 and 14 days in the general population, may last longer and be more painful in immunocompromised individuals. Pain is noted to increase upon eating salty, spicy or acidic foods and beverages as well as due to trauma when consuming hard or rough foods. Treatment involves the use of topical corticosteroids such as dexamethasone elixir (0.5mg/5ml) 5 ml swished for one minute then expectorated, or for more severe occurrences, systemic corticosteroids such as prednisone.  While the use of immunoactive agents contributes to a reduction in inflammation and therefore speeds healing, they do not immediately address pain issues.

Pain resulting from due to RAU is typically managed by using topical anesthetics or systemic analgesics. Whereas topical anesthetics do offer some relief from the pain associated with these lesions, such relief is usually of short duration. Another consequence of use of anesthetic mouthrinses is the numbing effect on the taste buds, which results in decreased desire to eat. Diminished nutritional intake further negatively impacts patients’ overall well-being. Systemic analgesics are somewhat effective, but do not specifically address localized pain associated with oral ulcerative disease.  A new over-the-counter oral formulation of 2-octyl cyanoacrylate (Orabase Soothe-N-Seal) has shown promise as a barrier product for managing localized oral pain due to ulcerative disease.21


  1. Arendorf TM, Bredekamp B, Cloete CA, Sauer G. Oral Manifestations of HIV infection in 600    South African patients. J Oral Pathol Med. 1998 Apr; 27(4): 176-9.

  2. Diz Dios P, Ocampo A, Miralles C. Changing prevalence of human immunodeficiency virus-associated oral lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000 October 403-4.

  3. Patton LL, McKaig R, Straauss R, Rogers D, Enron JJ Jr. Changing prevalence of oral manifestations of human immunodeficiency virus in the era of protease inhibitor therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:299-304.

  4. Tappuni AR, Flemming GJ. The effect of antiretroviral therapy on the prevalence of oral manifestations in HIV-infected patients: a UK study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001 Dec; 92(6):623-8.

  5. Aquirre JM, Echebarria MA, Ocina E, Ribacoba L, Montejo M. Reduction of HIV-associated oral lesions after highly active antiretroviral therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999 Aug 88(2):114-5.

  6. King MD, Reznik DA, O’Daniels CM, Larsen NM, Osterholt DM, Blumberg HM. Human Papillomavirus-Associated Oral Warts among HIV-Seropositive Patients in the Era of Highly Active Antiretroviral Therapy: An Emerging Infection. Clin Infect Dis 2002;34:641-8.

  7. Greenspan D, Canchola AJ, MacPhail LA, Cheikh B, Greenspan JS. Effect of highly active antiretroviral therapy on frequency of oral warts. Lancet 2001 May 5;357(9266):1411-2.

  8. Mascarenhas AK, Smith SR. Factors associated with utilization of care for oral lesions in HIV disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999 Jun;87(6):708-13.

  9. Magaldi S, Mata S, Hartung C, Verde G, Deibis L, Roldan Y, Marcano C. In vitro susceptibility of 137 Candida sp. isolates from HIV positive patients to several antifungal drugs. Mycopathologia. 2001;149(2):63-8.

  10. Cauda, R, Tacconelli E, Tumbarello M, Morace G, De Bernardis F, Torosantucci A,    Cassone A. Role of protease inhibitors in preventing recurrent oral candidosis in patients with HIV infection: a prospective case-control study. J Acquir Defic Syndr Hum Retrovirl, Vol 21(1), May 99. 

  11. Powderly WG, Mayer KH, Perfect JR. Diagnosis and treatment of oropharyngeal candidiasis in patients infected with HIV: a critical reassessment. AIDS Res Hum Retroviruses 1999 Nov 1;15(16):1405-12.

  12. Maenza JR, Keruly JC, Moore RD, Chaisson RE, Merz WG, Gallant JE. Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients. J Infect Dis 1996 Jan;173(1):219-25.

  13. Cartledge JD, Midgley J, Gazzard BG. Non-albicans oral candidosis in HIV-positive patients. J Antimicrob Chemother 1999 Mar;43(3):419-22.

  14. Lamster IB, Grbic JT, Mitchell-Lewis DA, Begg MD, Mitchell A. New concepts regarding the pathogenesis of periodontal disease in HIV infection. Ann Periodontology.1998 Jul;3(1):62-75.

  15. Yeung SC. HIV infection and periodontal disease. Ann R Australas Coll Dent Surg 2000 Oct;15:331-4.

  16. Glick M, Muzyka BC, Salon LM, Luric D. Necrotizing ulcerative periodontitis: a marker for severe immune deterioration. J Periodontol 1994;65:393-97.

  17. National Health and Nutrition Examination Survey (NHANES) III, National Center for Health Statistics (NCHS) of the Centers for Disease Control (CDC), 1996.

  18. Engles EA. Human Immunodeficiency virus infection, aging and cancer.  J Clin Epidemiol 2001 Dec;54 Suppl 1:S29-34.

  19. Baillargeon J, Deng JH, Hettler E, Harrison C, Grady JJ, Korte LG, Alexander J, Montalvo E, Jenson HB, Gao SJ. Seroprevalence of Kaposi's sarcoma-associated herpesvirus infection among blood donors from Texas. Ann Epidemiol 2001 Oct;11(7):512-8.

  20. Younai FS, Marcus M, Freed JR, Coutler ID, Cunningham W, Der-Martirosian C, Guzman-Bercerra N, Shapiro M. Self-reported oral dryness and HIV disease in a national sample of patients receiving medical care. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001 Dec;92(6):629-36.

  21. Kutcher MJ, Ludlow JB, Samuelson AD, Campbell T, Pusek SN. 2001. Evaluation of a bioadhesive device for the management of apthous ulcers. JADA 132:383-376.


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