HIV, or human immunodeficiency virus, is a pathogen responsible for developing acquired immunodeficiency syndrome (AIDS). When people become infected with HIV, their T-lymphocytes, especially CD4+ T-lymphocytes are damaged, leading to weakened immune system [1-4]. As immune deficiency progresses, it can result in various life-threatening complications, a condition known as AIDS. The World Health Organization (WHO) considers HIV a major global health issue [5]. In 2024, it is estimated that 39 million people worldwide are living with HIV, with 1.3 million new infections and 42 million deaths from AIDS-related illnesses reported [5]. In Korea, 1,005 new HIV cases were recorded in 2023, a decrease of 61 (5.7%) from the previous year’s 1,066 cases, bringing the total number of people living with HIV in Korea to 19,745 [6].

Oral lesions are often among the earliest and most significant indicators of HIV infection [1,2,7,8]. They indicate a drop in CD4+ T-lymphocyte levels and a rise in viral load, acting as standalone indicators of disease progression [1,2,7]. There are 10 common oral manifestations of HIV infection: oral candidiasis (OC), oral hairy leukoplakia (OHL), mucosal hypermigration, HIV-related salivary gland disease, HIV-related non-specific oral ulceration, recurrent aphthous stomatitis (RAS), periodontal & gingival disease, Kaposi’s sarcoma (KS), herpes simplex virus (HSV) infections, and human papillomavirus (HPV) infections [3]. When an individual’s HIV status is unknown, these oral lesions are strongly indicate HIV infection, leading to early diagnosis and prompt treatment [7]. In asymptomatic patients, who may be unaware of their infection, dentists are often the first to recognize these oral lesions. Therefore, dentists should conduct thorough oral examination for all HIV-positive patients and those suspected of being at risk for HIV infection at all stages of diagnosis and management [7].

In this study, we investigate the oral manifestations of HIV in two HIV-positive patients and emphasize the importance of HIV screening. This study was approved by the Institutional Review Board (IRB) of Pusan National University Dental Hospital (PNUDH), which waived the requirement for informed consent (IRB No. PNUDH-2024-08-010).

1. Case 1

A 57-year-old man presented to the Department of Oral Medicine, PNUDH with a generalized soreness in his mouth when eating spicy or salty foods and a mass on his tongue. The patient reported that these symptoms had started 6 months ago, and had fluctuated, improving and worsening depending on his physical condition. His medical history was unremarkable, with no unusual findings such as diabetes or hypertension, and he had no recent dental issues.

Panoramic radiographs showed generalized alveolar bone loss with calculus deposition and several caries. Clinical examination showed a removable whitish lesion with generalized erythematous and ulcerative lesions in the oral cavity, and a fibroma-like mass proliferation on the right buccal mucosa. Sialometry indicated hyposalivation with non-stimulated salivary flow rate of 0.1 mL/min and stimulated salivary flow rate of 0.3 mL/min.

Based on the following clinical findings and history, erosive oral lichen planus (OLP), OC were tentatively diagnosed (Fig. 1). A same-day removal of fibroma-like mass using diode laser (EPIC 10, BIOLASE) due to the patient’s discomfort and his imminent travel plans. Prior to excising the mass from the right buccal mucosa, we conducted infection screening tests for hepatitis C virus (HCV) and HIV, including OraQuick ADVANCE rapid HIV-1, 2 antibody (Ab) test, and HCV Ab tests. The HIV test result was positive, prompting additional blood tests including a complete blood count (CBC), liver function test (LFT), renal function test (RFT), fluorescent antinuclear antibody (FANA), rheumatoid factor (RF), and anti-HIV tests.

The patient was prescribed oral corticosteroids (Solondo Tab, Yuhanmedica Inc.) for 7 days, with a daily dosage of 10 mg of prednisolone, to address the erosive lesions. He was also instructed to use a corticosteroid gargle (0.12% prednisolone solution) for 5 to 10 minutes, three times a day. To treat OC, a topical antifungal agent (PMS-Nystatin suspension, Pharmascience Inc.) was prescribed. Additionally, a corticosteroid ointment (Esperson gel, Handok Inc.) was recommended for application three times a day for 1 week, to be applied three times daily. At the second visit, there was no significant improvement, and the patient did not return for follow up due to personal reasons. The blood tests confirmed a positive anti-HIV result, and the histopathological examination showed lymphocytic infiltration in superficial dermis and epidermis. The patient was informed about the requirement to report HIV infection and was referred to the Department of Infectious Diseases.

2. Case 2

The 61-year-old man presented to the Department of Oral Medicine at PNUDH with complaints of dry mouth, a burning sensation, and fissures at the corners of mouth, which began after tooth extractions and implantations over a 6-month period. The patient reported that these symptoms started 5 months ago and that although he had been prescribed medication to stimulate salivation intermittently, he did not notice significant improvement. He smokes 1 pack of cigarettes per day and has no other notable medical history.

Clinical examination revealed OC on the bilateral buccal mucosa, median rhomboid glossitis on the posterior part of the tongue, and nicotine stomatitis on the palate. Sialometry conducted during the initial examination showed a non-stimulated salivary flow rate of 0.75 mL/min and a stimulated salivary flow rate of 1.75 mL/min, with no hyposalivation observed. Blood tests (CBC, LFT, RFT, erythrocyte sedimentation rate [ESR], iron, C-reactive protein [CRP], VitB12, B6, Folate, FANA, RF, Zinc) showed no significant abnormalities. A Candida culture from an oral swab indicated Candida growth. The patient was prescribed corticosteroid gargle (0.06% prednisolone solution) for the stomatitis and topical antifungal agent (PMS-Nystatin suspension, Pharmascience Inc.) for the OC. Periodic Candida swabs were performed, and subsequent re-cultures were negative. Due to improvement, the patient was scheduled for a routine checkup.

One year later, the patient returned, reporting that his oral symptoms had recurred 2 months before the visit (Fig. 2). He mentioned that he had recently undergone an endoscopy at an internal medicine clinic, which suggested a suspected fungal infection in the esophagus, and that he had lost about 10 kg due to difficulty eating. Three weeks after the first visit, he was referred to the Department of Infectious Diseases because his condition did not improve despite continued use of topical antifungal agents. Blood tests revealed decreased CD4+ T cell counts (10.5/µL), and a positive HIV Ab result, leading to a diagnosis of HIV infection.

Oral manifestations of HIV infection are a crucial aspect of the clinical presentation, with a reported prevalence ranging from 30% to 80% [1,2,4,8]. These oral symptoms can not only indicate an early progression to AIDS but also increase in frequency with worsening immunosuppression [1,9]. This suggests that oral conditions may serve as predictors of immunosuppression and disease progression [1,9]. Beyond this, maintaining good oral health is essential for overall well-being. Masticatory discomfort can impair nutrition, and oral pain, along with functional issues, can negatively impact systemic health [10].

Oral manifestations associated with HIV have traditionally been classified using the European community (EC)-Clearinghouse on problems related to HIV infection and the WHO Collaborating Center on Oral Manifestations of the Immunodeficiency Virus (EC-Clearinghouse-WHO) criteria developed in 1993 [11]. This classification is appreciated for its straightforwardness and practicality. It organizes the lesions into three categories based on their relationship with HIV infection: lesions strongly associated with HIV infection, lesions less commonly associated with HIV infection, and lesions seen in HIV infection (Table 1) [11]. Although this classification remains widely accepted, the 8th World Workshop for Oral Health and Disease (WWOHD) in HIV/AIDS recently identified 10 conditions consistently reported in HIV patients. These include OC, OHL, mucosal hyperpigmentation, periodontal & gingival disease, RAS, HIV-related non-specific oral ulceration, HIV-related salivary gland disease, KS, HSV infection, and HPV infection [3,12].

OC is the most common opportunistic infection among HIV/AIDS oral manifestations [13-15]. It often affects patients with underlying health issues, like immunosuppressive disease or blood disorders. This condition is commonly triggered by disruptions in the oral microbiome caused by treatment such as immunosuppressants, chemotherapy, radiation to the mouth or the salivary gland, corticosteroids, or broad-spectrum antibiotics [15]. While OC is not exclusive to HIV, low CD4+ T cell counts are critical factor in its pathogenesis, with incidence increasing when counts fall below 200 cells/µL [13,15]. Thus, OC can be an early sign of HIV-related immunodeficiency and may also indicate disease progression [15,16]. Pseudomembranous candidiasis (oral thrush) is the most typical clinical presentation of among all OC, followed by erythematous candidiasis and angular cheilitis [8,12,14]. Pseudomembranous OC is characterized as single to multiple white, curdy plaques on the oral mucosal surface, often revealing a hemorrhagic, erythematous surface beneath when wiped [8,15]. Esophageal involvement should be considered if pseudomembranous candidiasis is widespread and accompanied by severe dysphagia [7,14]. Candidiasis involving both the oral cavity and esophagus is particularly common in HIV patients [17]. Erythematous candidiasis appears as flat red lesions on the palate and dorsum of the tongue, with a gloosy, depapillated or keratin loss appearance [2,7]. Angular cheilitis typically occurs at the mouth’s corners or commissures, as the word implies, presenting as erythematous fissures or crusts [15].

OHL is known to be caused by Epstein–Barr virus infection [18]. OHL has also been reported in immunocompetent patients, but is important in that it can serve as an early diagnostic indicator of immunocompromised patients or HIV infection [18]. OHL is characterized by thick, white lesions on the lateral borders of tongue, with hair-like vertical projections and corrugations [18,19]. Unlike OC, these lesions do not clear when rubbed [8].

In case 1, the patient was diagnosed with HIV during a medical examination at Pusan National University Hospital in January 2020, but this diagnosis was not reported to the Korea Disease Control and Prevention Agency (KDCA). When the patient later visited the Department of Oral Medicine at PNUDH, he claimed no significant medical history. Although some patients may be unaware of their HIV status, others may intentionally conceal it. Oral manifestations can be crucial in such differential diagnoses. The patient presented with and erosive lesions and a removable whitish lesion, initially diagnosed as erosive OLP and OC. The presence of a hypertrophic mass, not typical of OLP, raised suspicion of other conditions, leading to HIV screening test.

In case 2, despite initially responding to antifungal medication, the patient did not improve at the second visit and was found to have a suspected fungal infection in the esophagus. The presence of oral and esophageal candidiasis suggested an immunocompromised state, prompting a referral to the infectious disease department, where HIV infection was confirmed.

The key takeaway from these cases is that oral manifestations can play a significant role in the early diagnosis of HIV infection. Although none of the oral manifestations are unique to HIV/AIDS, they are more prevalent, severe, and progressive compared to HIV-negative individuals [1,2]. Since 2006, the Centers for Disease Control and Prevention has recommended that everyone aged 13 to 64 be tested for HIV at least once as part of routine health care. Thanks to ongoing antiretroviral therapy and viral suppression, most people with HIV now have life expectancies comparable to those without HIV. The significant reduction in HIV-related mortality has turned the disease from a once untreatable condition into a manageable chronic illness with the potential for long-term survival [1,2,7,12,20]. Thus, oral manifestations of HIV are crucial for early sign of recognition, diagnosis, and progression to AIDS. Dentists should take a thorough history, perform a comprehensive oral examination, and conduct an HIV screening test if any of the identified conditions are observed.

Soo-Min Ok and Hye-Min Ju serves on the editorial board of the Journal of Oral Medicine and Pain. But they have no role in the decision to publish this article. Except for that, no potential conflict of interest relevant to this article was reported.

Data sharing is not applicable to this article because no new data were created or analyzed in this study.

This study was supported by Clinical Research Grant, Pusan National University Dental Hospital (2024).

Conceptualization: HWK, HMJ. Data curation: SMO, SHJ, YWA. Formal analysis: SMO, SHJ, YWA, HMJ. Funding acquisition: HMJ. Methodology: SMO, SHJ. Project administration: HMJ. Visualization: HWK. Writing - original draft: HWK. Writing - review & editing: HMJ.