Human Immunodeficiency Virus/AIDS

Clinical presentation
Differential diagnosis
Marker for HIV
Nutritional implications
Solitary, multiple, or confluentvesicles; keratinized mucosa; painful
Apthous ulcers, CMV
Acyclovir 800 mg five times a day or valacyclovir 500 mg BID for 14 d
Increases in frequency and severity based on progression of HIV
Not generally; indicates disease progression
Dehydration, restricted oral intake
Nonspecific >5 mm ulcers, nonkeratinized mucosa; painful
HSV, recurrent aphthous ulcers
Ganciclovir; acyclovir (solely for oral lesions)
CD4 cell count <200 mm3
Not generally; indicates disease progression
Dehydration, restricted oral intake
Unilateral, generally on palate, along division of 5th cranial nerve; similar to HSV lesions; painful
Supportive and preventive; occasionally with oral or, if needed, intravenous acyclovir
No relation found
Not generally
Dehydration, restricted oral intake
Lateral borders of the tongue; a white, vertical, hyperkeratotic striae; cannot be wiped or rubbed off; asymptomatic
Hyperplastic or chronic candidiasis
Acyclovir 800 mg five times a day for 14 d
CD4 cell count <200 mm3; viral load >20,000 copies/mL
Red, purplish-blue macules or nodules; hard/soft palate, gingival; painful; caused by trauma
Bacillary (epithelioid) angiomatosis, lymphoma
Radition, surgical intervention; vinblastine sulfate 0.1 mg/mm2 or sodium tetradecyl sulfate 0.1 mg/mm2
CD4 cell count <100 mm3
Difficulty eating with larger and/or traumatized lesions
Hyperplastic, papillomatous or verrucous
Topical podophyllum resin 25%; intralesional injections one to two times a wk with 1 million IU/cm2 of the lesion, along with subcutaneous interferon-α injection of 3 million IU two to three times per wk
No relation found
Interference with chewing
HSV herpes simplex virus; CMV cytomegalovirus; VZV varicella zoster virus; EBV Epstein-Barr Virus; HHV8 human herpes virus 8; HPV human papilloma

Fungal Etiology

Table 14.2 describes the fungal oral lesions common in HIV disease [26].


Candidia albicans is common in the normal oral flora in many immunocompetent individuals, generally without any signs of clinical manifestation. Candidiasis, or candidosis, has been recognized as one of the most common and earliest intraoral manifestations of immune suppression [60]. While, not pathognomonic for HIV disease, oral candidiasis may be an early sign of infection and a marker for disease progression, independent of CD4 lymphocyte count [61]. The clinical diagnosis should be verified by laboratory tests such as cytological smear with potassium hydroxide, culture or biopsy and staining for tissue infiltration of pathogenic agents (spores or hyphae). Oral candidiasis may present in different forms including: pseudomembranous, erythematous, hyperplastic, angular chelitis and occasionally invasive oral ulceration. Differences in the risk factors associated with the different types of candidiasis in HIV may reflect distinct pathological mechanisms and it is possible that each form of oral candidiasis may denote a different stages of immune suppression [62].
The Intervention Review conducted via the Cochrane HIV/AIDS Group regarding “prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children” was based primarily on treatment trials [63]. The review found only one trial using food products in the form of lemon juice or lemon grass but no benefit was seen [63].
Pseudomembranous Candidiasis
Commonly known as thrush, pseudomembranous candidiasis presents as white or yellowish, plaque (s) that can be rubbed off the oral mucosa leaving an erythematous or bleeding surface. The plaques may be found on any intraoral surface. Patients may not be aware of the intraoral presentation or may be symptomatic with sensitivity and taste change that may affect oral feeding and, consequently, impact nutritional status. Oral candidiasis, particularly in immunocompromised and myelsuppressed patients may extend regionally to the throat and esophagus. The manifestation is an early indication of immune suppression, with CD4 cell counts below 400 cells per mm3 [64].
Erythematous Candidiasis
Erythematous candidiasis (also known as atrophic candidiasis) presents as red or atrophic patches that may affect any intraoral mucosal surface but has a predilection for the tongue and the hard palate. On the dorsal surface of the tongue, it manifests as areas of depapillation resulting in smooth, erythematous patches. The erythematous form of candidiasis presents alone or in combination with the pseudomembranous form. Lesions may be accompanied with a burning sensation and rarely ulceration [30]. The lesions can appear throughout the course of HIV disease, although they are generally seen during the earliest stages of immune suppression [37].
Treatment of both the pseudomembranous and erythematous forms of candidiasis is usually effective although recurrence is common in people where the underlying risk for infection is not effectively managed. Troches and mouth rinses are beneficial for patients with CD4 cell counts above 150 to 200 cells per mm3. In patients with more severe immune suppression, systemic medications should be instituted. Systemic medication may be more convenient that topicals [65].
Several factors should be considered when selecting the medication to be used. Troches are more convenient and practical than mouth rinses, but may not be dissolved in those with excessively dry mouth. Rinses sweetened with sugar should be avoided especially in dentate patients with dry mouth. The type and use of systemic medications are dictated by patient’s immune status, liver status, and compliance and the potential for drug interactions. Topical antifungal agents include nystatin oral pastille, one or two or pastilles dissolved slowly four or five times daily; clotrimazole oral troche 10 mg, one troche dissolved five times a day; and nystatin or itraconazole oral suspensions. It is important to note that nystatin suspension is highly sucrose sweetened. When these are chosen, patients need to be instructed in oral hygiene and home fluoride applications. Topical agents with low sugar content are vaginal preparations of clotrimazole or nystatin. One vaginal troche is dissolved in the mouth three times a day. However, the taste of the vaginal formulation is less agreeable to patients and may affect compliance. A new product with slow release intraorally is Oravig®. The most frequently used systemic antifungal agents are fluconazole one or two 100 mg tablets daily [65, 66].
Oral candidiasis has a high recurrence rate, and maintenance therapy may be indicated. In resistant cases, resistant speicies or selection of resistant Candida albicans may be overcome with increased dose of fluconazole or other agents such as voirconazole. Liver function and drug interaction must be considered with use of these systemic antifungals [65].
Hyperplastic Candidiasis
Hyperplastic candidiasis is uncommon among HIV-infected patients. This form of candidiasis may be seen in patients with severe immune suppression, represented by CD4 cell counts below 100 cells per mm3. Patients with hyperplastic candidiasis have a high predilection for having, or developing, esophageal candidiasis, which is an AIDS-defining illness [2].
Hyperplastic candidiasis presents as white or discolored plaques that may be solitary or confluent but, in contrast to pseudomembranous candidiasis which cannot be wiped or rubbed off the mucosa. The differential diagnosis includes oral leukoplakia and squamous cell carcinoma. The lesions may be found on any intraoral surface but have a high prevalence on the hard or soft palate [65].
Hyperplastic candidiasis is often misdiagnosed as leukoplakia or, when it presents on the tongue, as OHL. Even though the clinical manifestation of the lesion is pathognomonic, the presence of hyphae and blastospores on biopsy confirms a diagnosis. Treatment for this type of candidiasis involves systemic antifungal agents, which may include intravenous formulations [65].
Angular Chelitis
Angular chelitis presents as radiating red fissures, and occasionally with a pseudomembrane, in the corners of the mouth. This condition is frequently observed in older individuals with ill-fitting complete dentures and is not pathognomonic for HIV disease. It is commonly associated with xerostomia, a habit of licking the corners of the mouth, chronic use of petrolatum on the lips, over-closure of the jaw and systemic risk factors noted above [67, 68].
Treatment of angular chelitis is accomplished by application of a topical antifungal agent such as clotrimazole, miconazole, ketoconazole cream, or nystatin ointment in combination with a topical antibacterial agent. As the source of the organism is commonly oral, treatment of the oral cavity is often required. Nutritional deficiency can both contribute to angular cheilitis and be exacerbated by it [69].


Infections with histoplasmosis may occur in endemic areas, such as the Ohio and Mississippi valleys, and the inland areas of California. Histoplasmosis is caused by inhaling the spores of Histoplasma capsulatum, found in the soil throughout the world. Although rare in areas that are nonendemic, endemic areas have exhibited prevalence rates of approximately 70% of the adult population having a positive histoplasmin test [70]. In the immunocompetent host, infections by H. capsulatum are usually subclinical and self-limiting. However, in immunocompromised patients, H. capsulatum can cause a serious opportunistic infection. Although not correlated with CD4 cell count, histoplasmosis was included in the AIDS-defining illnesses category in 1985 [3]. Many cases of histoplasmosis are disseminated by the time of oral manifestations [71]. The clinical presentations vary along a spectrum of ulcerations to granulomas. A definitive diagnosis is based on clinical examination, serology, biopsy and culture [71]. The treatment of choice is forms of intravenously delivered amphotericin B, however itraconazole and ketoconazole have also been used successfully to treat disseminated histoplasmosis in immunocompromised patients [71, 72]. Newer agents such as voriconazole, micfungin may play an important role in treatment.

Table 14.2

Fungal infections
Oral manifestations
Clinical presentation
Differential diagnosis
Marker for HIV
Nutritional implications
Pseudomembranous candidiasis
White or yellowish, single or confluent plaques; easily rubbed off; any surface
Nystatin oral pastille, one to two pastilles dissolved slowly four to five times a day; clotrimazole oral troche 10 mg, 1 troche dissolved five times a day; nystatin oral suspension; fluconazole one to two 100 mg tables QD
CD4 cells below 400 cells/mm3
Not generally indicates early immune suppression
In severe cases, eating abd swallowing can be uncomfortable
Erythematous candidiasis
Red or atrophic patches on any surface, however, greater on the tongue and hard palate
Same as pseudomembranous
Any stage of HIV
Not generally, indicates early immune suppression
Longstanding lesions may produce a burning sensation
Hyperplastic candidiasis
White or discolored plaques; solitary or confluent; cannot be rubbed or wiped off
Leukoplakia, OHL
Fluconazole, one to two 100 mg tablets QD; ketoconazole one to two 200 mg tablets QD taken with food; itraconazole two 100 mg capsules QD
CD4 cell count below 100 cells per mm3 high predilection for either having or developing esophageal candidiasis
Yes, severe immune suppression
Burning sensation and a feeling of having a “large ball of cotton in the mouth”;xerostomia eating and swallowing may be uncomfortable
Angular chelitis
Radiating red fissures; commissures of the lips
Ketoconazole ointment 2%;apply to affected areas four times a day for 14 d
Difficulty opening the mouth because of pain

Bacterial Etiology

Periodontal disease

Periodontal disease is common in both HIV-positive and HIV-negative individuals. HIV-infected individuals may have more rapidly progressive periodontal disease, but this is not a consistent feature. Acute, rapidly progressive periodontal conditions may be early signs of immune suppression and HIV infection [37]. An association between aggressive periodontal conditions in HIV-infected individuals and a progressive deterioration of individuals’ immune status has been suggested [73, 74]. These periodontal conditions in the HIV-infected individual are linked to the person’s immune status, not change in the microflora [37]. There are three types of periodontal conditions that have been associated with HIV disease: linear gingival erythema (LGE), necrotizing ulcerative gingivitis (NUG), and necrotizing ulcerative periodontitis (NUP) [27, 75].
Linear Gingival Erythema
An erythematous 2–3 mm red band at the gingival margin, disproportional to plaque accretion, characterizes LGE with an equal distribution around the teeth without ulceration, and no increase in pocket depth with periodontal attachment loss, and minimal bleeding on probing [37]. Occasionally, punctuated or diffuse erythema is noted on the attached gingiva near the alveolar mucosa. The condition may be asymptomatic. This presentation does not have a strong correlation with HIV disease [37]. The differential diagnosis includes localized effect secondary to hyposalivation and dry mucosa, localized candidiasis, oral lichen planus, mucous membrane pemphigoid, hypersensitivity reaction presenting as plasma cell gingivitis, Geotrichum candidum infection, and thrombocytopenia. The presentation of LGE may be associated with subgingival Candida infection [37].
LGE will typically not respond to routine dental scaling and root planing. However, concomitant use of chlorhexidine gluconate (0.12%) mouth rinse generally causes improvement. The patient should be advised to swish with 15 mL of the solution for 30 seconds and expectorate. Addition of a topical antifungal agent may be advantageous. Meticulous oral hygiene is essential for treatment and maintenance [37].
Ulcerative Gingivitis and Ulcerative Periodontitis
Both NUG and NUP may represent stages in a spectrum of the same severe periodontal condition. NUG is classically limited to the gingiva, whereas NUP is recognized by the loss of periodontal attachment and ulceration of the adjacent alveolar mucosa. Both lesions manifest in the acute phase and may vary from initial lesions with restricted necrosis at the top of the papillae to involvement of the complete attached gingiva, accompanied by tooth mobility and bone sequestering, [73], and both may become chronic. Individuals with NUP generally experience deep-seated jaw pain, spontaneous bleeding, and, in chronic cases, tooth movement [26, 76, 77]. Bad taste or bad breath may be present. Left untreated, NUP may progress with 1–2 mm of soft and hard tissue destruction per week. NUP has been linked with severe immune suppression and CD4 cell counts below 100 cells per mm3 [73]. During the acute phases, oral intake may be severely limited.
Differential diagnosis may include: mucous membrane pemphigoid, erythema multiforme, and acute leukemia [37].
The first step in the treatment of both NUG and NUP is debridement and antibiotic therapy with metronidazole 250–500 mg or tetracycline 250–500 mg QID for 7 days. Pain relief is rapid and tissue healing begins quickly. Concomitant antifungal therapy is recommended. Chlorhexidine gluconate 0.12% mouth rinse, twice a day swish for 30 seconds and then expectorate, is recommended for treatment and maintenance therapy [37].

Conditions with Nonspecific Etiology

Necrotizing Stomatitis

Necrotizing stomatitis is a rapidly progressive localized necrosis of oral soft tissue overlying bone [78]. The lesion may be extremely painful and interfere with eating, speech, and swallowing, seen in severely immunosuppressed, with the CD4 cell counts below 100 cells per mm3 [2].
Differential diagnosis should include aggressive forms of aphthous ulcers, traumatic ulcers and malignant disease. It has been hypothesized that necrotizing stomatitis may be representing a widespread form of NUP [37].
Treatment includes debridement of the necrotic areas. A stent should be fabricated to cover the affected area to protect from trauma and as a carrier for topical application of medication. Topical glucocorticosteroids such as clobetasol or fluocinonide gel, or steroid mouth rinse may be used. In more severe and resistant cases, systemic steroid such as prednisone up to 80 mg day for 7 days may be indicated. The patient should be instructed to use chlorhexidine gluconate 0.12% rinse twice a day. Concurrent systemic antibiotics, metronidazole or tetracyclines (minocycline, doxicycline) may prevent bacterial super-infections and promote healing [37]. Pain management should be provided as needed.

Aphthous Like Ulcers

People living with HIV may experience ulcerations clinically resembling aphthous ulcers but lacking the usual early age predilection [79]. Minor recurrent aphthous ulcers generally manifest as 2–5 mm diameter small ulcers and resolve within 5 to 7 days. Recurrent aphthous stomattis (RAS) typically appear on non-keratinized tissue of the oral cavity, such as inside the lips or on the floor of the mouth or buccal mucosa. Minor RAS are characterized by frequent recurrence rate, often at the same site, and are generally associated with stressful events [37]. These lesions may be particularly painful and when large lesions develop may heal with scarring. Minor ulcerations may be misdiagnosed as recurrent herpes virus infection. Anesthetic or analgesic mouth washes or coating agents may ease local pain. Pain management may restore a patient’s ability to eat, drink, chew, and swallow.
Recurrent ulcers that present as greater than 10 mm in diameter, with a crateriform and deeply eroded base, are known as major recurrent aphthae. These ulcers persist for more than 3 weeks and may heal with scarring. Major RAS severely impact oral intake, speech and swallowing [80]. Although no clear etiology has been established for these ulcers, several theories have been put forth: stress, vitamin deficiency, diet, hormonal changes, trauma, and immune dysfunction [30, 81]. In patients with HIV disease, major RAS have been correlated with severe immune suppression and severe persisting lesions associated with CD4 cell count below 100 cells per mm3 [80].
Treatment of major RAS is crucial to maintaining oral intake. Topical glucocorticosteroids may be administered as the first step in therapy. If severe lesions are present, systemic prednisone may be provided. Topical steroid rinses such as dexamethasone elixir 0.5 mg/5 mL, 15 mL four times a day or other topical steroid rinses compounded may be used when multiple oral sites or those not amenable to local application of gel or ointment, such as in the posterior oropharynx. Antibiotic and an antifungal may be prescribed to prevent superinfections. Thalidomide 100–200 mg/d has been used to treat oral and esophageal ulcerations with limited success [82, 83]. There are some adverse reactions with use of thalidomide,and specific precautions required in its prescription and use [83]. Other topical immunosupporesives may be considered as may agents that reduce TNF production. Pain management is an important consideration in management to support comfort and oral intake.

Neoplastic Conditions

The association between HIV, immunusppression and non-Hodgkin’s lymphomas (NHLs) was recognized early in the HIV epidemic and in 1985 it was added to the list of AIDS-defining diseases [3]. This neoplasm is rare, appearing in approximately 3% of AIDS diagnoses worldwide [84]. The lesion may present as a large, painful, ulcerated or exophytic mass on any mucosal surface and may be accompanied with tooth mobility, jaw pain, widened periodontal ligament, and progressive paresthesia [30, 37]. The average CD4 cell count in patients diagnosed with NHL is below 100 cells per mm3 [30]. Prior to HAART, NHL represented the second most common neoplasm associated with AIDS, after KS [85]. With the implementation of HAART, the incidence of KS cases has decreased, whereas the number of patients developing NHL remain the same and with extended survival may be seen more commonly [85].
A biopsy is required for a definitive diagnosis of NHL, and an appropriate referral to an oncologist is indicated for initiation of treatment. Therapy may include surgical excision, chemotherapy, and/or radiation therapy [30]. NHL in HIV infected individuals used to be associated with a poor prognosis [86]. Progress in the treatment of NHL has significantly improved the prognosis of this disease in HIV but the survival rates for HIV patients with NHL remain below that of non-HIV patients [87].
A patient, with or without HIV infection, who has a neoplastic diagnosis will likely have impact on the oral cavity in numerous ways that require dietary and nutritional consideration. A series of recent reviews for head and neck cancer by Epstein and Huhmann portray needs while undergoing therapy [88] and post therapy [89]. The impacts include assuring adequate caloric and nutrient intake. Much of the focus need be on adapting diets to the functional limitations resulting from chemo- or radiation therapy. Obvious preference would be for cancer prevention, for which diet and nutrients have been shown to play a role, particularly through the consumption of fruits and vegetables [90].

Nutritional Management of Oral Manifestations of HIV

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Nov 4, 2015 | Posted by in General Dentistry | Comments Off on Human Immunodeficiency Virus/AIDS
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