Policy for prevention of oral manifestations in HIV/AIDS: the approach of the WHO Global Oral Health Program

The HIV/AIDS pandemic has become a human and social disaster, particularly affecting the developing countries of Africa, Southeast Asia, and Latin America. By the end of 2004, about 40 million people were estimated to be infected by HIV globally. The health sectors in many affected countries are facing severe shortages of human and financial resources, and are struggling to cope with the growing impact of HIV/AIDS. In most developed countries, the availability of antiretroviral treatment has resulted in a dramatic reduction in HIV/AIDS-related mortality and morbidity. In contrast, in the developing countries, there is little access to treatment, and access to HIV-prevention services is poor. The '3 by 5' initiative was launched by the WHO and UNAIDS in 2003 with the aim of providing antiretrovirals to three million people in developing countries by the year 2005. HIV infection has a significant negative impact on oral health, with approximately 40-50% of HIV-positive persons developing oral fungal, bacterial, or viral infections early in the course of the disease. Oral health services and professionals can contribute effectively to the control of HIV/AIDS through health education and health promotion, patient care, effective infection control, and surveillance. The WHO Global Oral Health Program has strengthened its work for prevention of HIV/AIDS-related oral disease. The WHO co-sponsored conference, Oral Health and Disease in AIDS, held in Phuket, Thailand (2004), issued a declaration calling for action by national and international health authorities. The aim is to strengthen oral health promotion and the care of HIV-infected persons, and to encourage research on the impact that HIV/AIDS, public health initiatives, and surveillance have on oral health.     

Prevalence and classification of HIV-associated oral lesions

OBJECTIVES: An International Workshop addressed the prevalence and classification of HIV/AIDS associated oral lesions.
DESIGN: Five questions provided the framework for discussion and literature review. What is the prevalence of oral lesions in children and adults? Should the accepted classification of HIV-related oral lesions be modified in the light of recent findings? Why is there a gender difference in the prevalence of oral lesions in developed and developing countries? Are there unusual lesions present in developing countries? Is there any association between modes of transmission and the prevalence of oral lesions?
RESULTS: Workshop discussion emphasized the urgent need for assistance in the development of expertise to obtain accurate global prevalence data for HIV-associated oral lesions. Oral candidiasis has been consistently reported as the most prevalent HIV-associated oral lesion in all ages. Penicilliosis marneffei, a newly described fungal infection, has emerged in South-east Asia. Oral hairy leukoplakia and Kaposi's sarcoma appear to be associated with male gender and male-to-male HIV transmission risk behaviours. These lesions occur only rarely in children.
CONCLUSIONS: Additional prevalence data are needed from developing countries prior to substantially altering the 1993 ECC/WHO Classification of oral lesions associated with adult HIV infection. The workshop confirmed current oral disease diagnostic criteria.     

Oral lesions of HIV infection in developing countries

HIV infection has spread rapidly within developing countries since it was first recognized in the early 1980s. The purpose of this paper is to review the prevalence of oral lesions associated with HIV infection (oral HIV) in the developing world, and to identify additional factors that may complicate the presentation of these lesions. Direct comparison of regional and local prevalence studies within Africa, India and Thailand is speculative because there are few reports available. Furthermore, inherent differences in study design, data collection, standardization and calibration of health workers make any inferences inconclusive. Additional prevalence studies of oral HIV lesions associated with systemic disease or social conditions, such as poverty or malnutrition, are needed. In order to provide a basis for the diagnosis and treatment of HIV-associated oral lesions in the developing world, it is important to recognize any confounding factors that may impact on their presentation and management. Elucidation of these various factors may provide a basis for treatment within the developing and developed world.     

Oral lesions of HIV and AIDS in Asia: An overview

The magnitude of HIV infection in the Asian region is increasing dramatically. Oral disease represents an important health problem for HIV-infected individuals, because of its diagnostic, prognostic and therapeutic implications. The documentation and reporting of HIV infection and AIDS in most of the Asian countries has been superficial. Though the epidemiology of HIV infection in Asia has been studied by many investigators, few attempts have been made to summarise the data and assess the magnitude of the problem, the mode of transmission, the spread of infection and clinical pattern of illness. A review of the literature shows that there is hardly any published data on oral manifestations of HIV infection or AIDS from the Asian region. However, some preliminary information is available on the type of lesion presenting in patients from India and Thailand. These observations suggest that oral manifestations are common in HIV-infected and AIDS patients. The pattern of occurrence of various lesions reported appears to show variation from those reports from other parts of the world, but no definitive conclusion can be drawn from these preliminary observations. Further epidemiological studies are necessary to substantiate the present understanding of the nature of oral lesions found in Asian countries.     

The global changing pattern of the oral manifestations of HIV

The significance of the oral manifestations of HIV has been widely recognised since the start of the epidemic. It is estimated that more than 38 million people are living with HIV currently, with more than a third presenting with oral manifestations. Access to optimum clinical management and effective treatment in resource‐rich countries has led to a remarkable decrease in some of the oral manifestations in the HIV population but this is not mirrored in developing countries, where most HIV‐positive patients reside. In this paper, a review of the literature since the start of the HIV infection in different parts of the world is presented to highlight the current significance of the oral conditions in this population. Oral candidiasis was repeatedly reported as the most encountered oral manifestation of HIV in different countries, including in studies on groups on anti‐retroviral therapy. Over time salivary gland disease was reported less in developed countries but was encountered more in developing countries. There is evidence to show that the prevalence of oral warts increased with the establishment of anti‐retroviral therapy. A review of the worldwide prevalence of HIV‐related oral conditions indicates that except for oral hairy leucoplakia, the prevalence of all other nine commonly reported oral conditions remained the same or increased over time. Oral opportunistic infections in HIV‐infected patients are an ongoing clinical burden mainly in developing countries. Maintaining research in the subject and improving access to HIV treatment will help address the oral health inequalities around the world.     

Oral fungal and bacterial infections in HIV-infected individuals: an overview in Africa

Oral opportunistic infections developing secondary to human immunodeficiency virus (HIV) infection have been reported from the early days of the epidemic and have been classified by both the EC-Clearinghouse and the World Health Organisation (WHO). Among the fungal infections, oral candidiasis, presenting in African HIV-infected patients has been sporadically documented. We review the literature with respect to candidal carriage, oral candidiasis prevalence and the predictive value of oral candidiasis for a diagnosis of underlying HIV disease in African HIV-infected patients. The use of oral candidiasis as a marker of disease progression, the species of yeasts isolated from the oral cavity in Africa and the resistance of the yeasts to antifungal agents and treatment regimens are discussed. Orofacial lesions as manifestations of the systemic mycoses are rarely seen in isolation and few cases are reported in the literature from Africa. In spite of the high incidence of noma, tuberculosis, chronic osteomyelitis and syphilis in Africa, surprisingly there have been very few reported cases of the oral manifestations of these diseases in HIV-positive individuals. Orofacial disease in HIV-infected patients is associated with marked morbidity, which is compounded by malnutrition. The authors indicate specific research areas, initially directed at the most effective management strategies, which would complete data in this important area.     

Prognostic significance of HIV-associated oral lesions and their relation to therapy

The oral manifestations of HIV infection have been considered to be of value in assessing disease progression in the developed world. However, the potential use of oral lesions as prognostic markers in resource-poor countries has yet to be fully investigated. There is reasonably compelling evidence in the developed world for an association between oral lesions and viral load. However, the true nature of this association is less clear and there are few data available from the developing world. With the introduction of HAART, a change in prevalence of the oral manifestations of HIV infection has been observed, including regression of oral candidiasis, Kaposi's sarcoma and oral hairy leukoplakia. However, oral condylomata and herpes simplex virus infection appear to persist with HMRT therapy. Further research in partnership with resource-poor countries is required to document disease progression and the associated oral lesions in both adults and children.     

Oral manifestations of HIV infection in 600 South African patients

Arendorf TM, Bredekamp B, Cloete CAC, Sauer G: Oral manifestations of HIV infection in 600 South African patients. J Oral Pathol Med 1998; 27: 176-9. C Munksgaard, 1998. Oral lesions associated with HIV infection, as classified by the EC-Clearinghouse on Oral Problems related to HIV infection and the WHO Collaborating Centre on Oral manifestations of the immunodeficiency virus, were studied in 600 consecutive HIV-infected patients in Cape Town, South Africa. One or more lesions were seen in 60.4% of cases. Combined candidal lesions were evident in 37.8%, hairy leukoplakia in 19.7% and combined gingival/periodontal lesions in 8.5% of patients seen. Lesions less commonly recorded include oral ulceration (2.9%) and Kaposi's sarcoma (1.5%). The clinical range of lesions seen is similar to those reported elsewhere, but socio-cultural differences allowed no reliable comparison. More than a quarter of our patients had oral soft tissue discomfort necessitating treatment; in 3.3% these were the presenting symptom. This indicates a potential major public health concern requiring education in recognition and appropriate referral and management.     

Oral lesions and conditions associated with human immunodeficiency virus infection in 300 south Indian patients

BACKGROUND: Human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) is a major health problem in India. The National AIDS Control Organisation (NACO) of India reports a seropositivity of 25.03 per thousand for the whole country, as of October 1999. In spite of this high prevalence there are very few reports of oral lesions and conditions in Indian HIV/AIDS patients, which are important in early diagnosis and management of these patients. OBJECTIVE AND SETTING: The present report describes the oral lesions in 300 HIV positive symptomatic patients presenting to us at RAGAS-YRG CARE, a non-governmental organisation in Chennai, South India, over a period of 9 months in 1998. METHOD: Lesions were diagnosed on clinical appearance using international criteria. RESULTS: Of the 300 patients 89% had acquired the infection through heterosexual contact. There were 205 males and 95 females, aged from 7 months to 72 years. Forty-seven percent of the patients were in the age group 21-30 years. CD4 counts were ascertained for 105 patients, 64 (62%) had CD4 counts < or = 200. A total of 217 (72%) of the 300 patients had some oral lesion when examined. Gingivitis (47%) and pseudomembranous candidiasis (33%) were the most common oral lesions. The other oral lesions seen were oral mucosal pigmentation (23%), erythematous candidiasis (14%), periodontitis (9%), angular cheilitis (8%), oral ulcers (3%), oral hairy leukoplakia (3%), hyperplastic candidiasis (1%), oral submucous fibrosis (2%) and one case of leukoplakia. CONCLUSIONS: Oral lesions occur commonly in HIV infection. A comprehensive oral examination may not only suggest HIV disease but may also be useful in monitoring the disease progression. This is a cost-effective procedure, which may be useful in screening large populations in developing countries like India.     

Social aspects of HIV and their relationship to craniofacial problems: workshop 4C

The oral research community needs an understanding of the social causes, consequences, and costs of disease in relation to oral health. This workshop concluded that HIV infection constitutes a special dental need requiring specific arrangements to facilitate oral care for infected persons. Oral manifestations of HIV infection affect everyday life, but more evidence is needed on the effects of interventions to alleviate these impacts. Other oral health habits add to the burden of HIV/AIDS-associated oral diseases and compete with them for resources. These problems are most acute where the prevalence of HIV is high and resources are scarce. Effective health promotion is therefore important in these areas. Without data on the utility of oral health care in developing countries, practical approaches are guided by societal and multidisciplinary principles. There are also important ethical considerations.     

Oral mucosal leishmaniasis as a presenting feature of HIV infection and its management

Leishmaniasis is a chronic parasitic protozoal disease transmitted by sandfly vectors and is endemic in some regions of South America, Asia, Africa and Mediterranean countries. This case report describes a British patient who presented with oral mucosal leishmaniasis and in whom it was also the first sign of HIV disease. We believe it is the first reported case of isolated oral mucosal leishmaniasis as a presenting feature of otherwise unknown HIV infection.     

Dental considerations for the paediatric AIDS/HIV patient

HIV infection and AIDS are spreading rapidly among the world's children, especially among African-American and Hispanic children in the USA, and those in developing countries. Although recent research has identified several ways of preventing perinatal transmission of HIV, most of these methods are too expensive for widespread use in developing countries, where the epidemic is most severe. Oral manifestations are early and common clinical indicators of HIV infection and progression in children, as in adults, although the specific manifestations differ between adults and children. Oropharyngeal candidiasis is the most common sign of HIV infection in children and is significantly associated with markers of HIV disease progression. Other common oral manifestations in children include herpes simplex, linear gingival erythema, parotid enlargement and recurrent aphthous ulceration. Further research is needed on the ways in which oral manifestations can be used as predictors of disease progression; on the impact of the limited availability of health care for impoverished families who are disproportionately affected by HIV infection; and on supportive care and its impact on infected children's quality of life.     

Common oral opportunistic infections in Human Immunodeficiency Virus infection/Acquired Immunodeficiency Syndrome: Changing epidemiology; diagnostic criteria and methods; management protocols

There were 36.9 million in the world living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) as of 2017, and new infections have seen a reduction by 18% since 2010. But this rate of decline is not sufficient for the goal of eradication of AIDS by 2030. Only 21.7  million people infected with HIV have accesses to antiretroviral therapy, with the rest at risk of the potential complications of HIV infection. It has been shown that oral lesions are diagnostic and prognostic of HIV infection, and many oral opportunistic infections continue to be a major problem, particularly in developing countries. It is therefore important that dental surgeons be aware and updated to recognize and manage the oral effects of HIV infection/AIDS. This chapter describes the classification, diagnosis, and management of oral lesions in these patients, based on our current understanding of the infection. This review also discusses the standardization of diagnosis of oral lesions in HIV infection/AIDS patients, immune reconstitution inflammatory syndrome case definition, and the research priorities formulated at the 7th World Workshop on Oral Health and Disease in AIDS.     

Oral lesions, HIV phenotypes, and management of HIV-related disease: Workshop 4A

The workshop considered 5 questions related to oral lesions, HIV phenotypes, and the management of HIV-related disease, with a focus on evidence and challenges in resource-poor settings. First, are oral lesions unique with respect to geographic location or phenotype? Second, how useful would an oral lesion index be to predict HIV in resource-poor countries with no access to CD4 counts or viral load? Third, what are the latest methods and delivery modes for drugs used to treat oral lesions associated with HIV? Fourth, what is the role of the oral health care worker in rapid diagnostic testing for HIV? Fifth, what ethical and legal issues are to be considered when managing the HIV patient? The consensus of the workshop was the need for additional research in 4 key areas in developing countries: (1) additional investigation of comorbidities associated with HIV infection that may affect oral lesion presentation and distribution, especially in pediatric populations; (2) the development of region-specific algorithms involving HIV oral lesions, indicating cumulative risk of immune suppression and the presence of HIV disease; (3) well-designed clinical trials to test new therapies for oral lesions, new treatments for resistant oral fungal and viral diseases, effectiveness of therapies in children, and new drug delivery systems; and (4) the role of the oral health care worker in rapid diagnostic testing for HIV in various regions of the world.     

Oral innate immunity in HIV infection in HAART era

Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces not only provide a physical barrier but also produce different antimicrobial peptides, including human β‐defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co‐infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection, contributed to a global reduction of HIV‐associated oral lesions. However, prolonged use of HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: (i) What are the roles of oral innate immunity in health and disease?, (ii) What are the effects of HIV infection on oral innate immunity?, (iii) What are the roles of oral innate immunity against other co‐infections?, (iv) What are the effects of HAART on oral innate immunity?, and (v) Is oral innate immunity enhanced by HAART?     

Mouth cancer in inflammatory bowel diseases

Mouth cancer is a major health problem. Multiple risk factors for developing mouth cancer have been studied and include history of tobacco and alcohol abuse, age over 40, exposure to ultraviolet radiation, human papilloma virus infection (HPV), nutritional deficiencies, chronic irritation, and existence or oral potentially malignant lesions such as leukoplakia and lichen planus. An important risk factor for mouth cancer is chronic immunosuppression and has been extensively reported after solid organ transplantation as well as HIV‐infected patients. Diagnosis of inflammatory bowel disease (IBD) is not yet considered as a risk factor for oral cancer development. However, a significant number of patients with IBD are receiving immunosuppressants and biological therapies which could represent potential oral oncogenic factors either by direct oncogenic effect or by continuous immunosuppression favoring carcinogenesis, especially in patients with HPV(+) IBD. Education on modifiable risk behaviors in patients with IBD is the cornerstone of prevention of mouth cancer. Oral screening should be performed for all patients with IBD, especially those who are about to start an immunosuppressant or a biologic.     

Oral aspects of HIV infection in children

Most infants with congenital HIV infection appear normal at birth. Clinical difficulties usually begin as the first year proceeds, and in about half of the children oral manifestations are the first signs. Oral manifestations are commonly found in HIV-positive asymptomatic and pediatric AIDS patients, they are the earliest clinical signs of HIV infection and disease progression in children, and may be used as diagnostic markers, especially in developing countries. Studies have established an accurate association between oral manifestations and progression of HIV disease in children. Since the mouth is easily accessed for clinical examination, the important oral signs should be utilized in the diagnosis and early intervention of AIDS in these vulnerable populations.     

Oral manifestations of HIV infection in 36 Nigerian children

Oral manifestations of HIV/AIDS are early and common clinical indicators of HIV infection. There has been no report on the clinical prevalence of oral lesions associated with HIV infection in children in sub-Saharan Africa. We report the findings of a cross sectional study of 36 Nigerian children seen at the Pediatrics Infectious Disease Clinic of the AIDS Prevention Initiative in Nigeria (APIN), Jos University Teaching Hospital (JUTH) Jos, Nigeria.     

Some unusual oral lesions in HIV infection: Comments on the current classification

Of the numerous oral lesions reported in HIV-infected patients, four entities will be discussed in this paper: linear gingival erythema; cystic lymphoid hyperplasia of the parotid gland; oral non-Hodgkin's lymphoma; and oral squamous cell carcinoma. Based on the literature and the author's personal experience, it appears that linear gingival erythema is perhaps a specific HIV-associated periodontal lesion, but that insufficient data are available in the literature yet to classify this periodontal lesion as a lesion that is strongly associated with HIV infection. On the other hand, cystic lymphoid hyperplasia of the parotid gland has been rather widely reported and has characteristic histopathological features that would justify consideration of this lesion as highly indicative of an underlying HIV infection. Oral non-Hodgkin's lymphoma, at present regarded as a lesion ‘strongly associated with HIV infection’, is less characteristic in this respect and should merely be classified as ‘a lesion seen in HIV infection’. Oral squamous cell carcinomas, not included in the most recent International Classification of Oral Manifestations of HIV infection, should be listed in Group 3 of that classification, representing ‘lesions seen in HIV infection’. Further criteria should be developed that will enable distinctions to be made between lesions ‘strongly associated with’, ‘less commonly associated with’, and ‘seen in’ HIV infection.