(B2) Periodontal diseases and other bacterial infections

The workshop addressed the following questions with respect to periodontal diseases and bacterial infections seen in HIV infection: (1) What is linear gingival erythema? Is it prevalent only in HIV disease? A crude Delphi technique was used to ascertain whether LGE existed, but a consensus could not be reached. It was agreed that a diagnosis of LGE should be considered only if the lesion persists after removal of plaque in the initial visit. (2) Do periodontal pockets contribute to viremia in HIV infection? At present, the data are not available to answer this question. (3) Do anti-viral drugs reach the sulcular fluid in significant concentrations? No one at the workshop was aware of data that could answer this question. (4) Does concurrent tuberculosis infection modify the oral manifestations of HIV infection? Though analysis of data from the developing countries does suggest an association between tuberculosis and oral candidiasis, more data and multivariate analysis considering immunosuppression as a confounding factor are necessary, for any conclusions to be derived. (5) What pathogens are involved in periodontal diseases in HIV infection? Periodontal disease may be initiated by conventional periodontal pathogens. But the progression and tissue destruction depend upon the presence of typical and atypical micro-organisms, including viruses, their by-products, increased secretion of potentially destructive inflammatory mediators, and overwhelming host response. (6) How can we diagnose the diseases seen in HIV infection? The answer can be obtained only with data from controlled and blinded studies. It is necessary to design collaborative multi-center longitudinal studies. The results obtained from such large sample sizes can contribute eventually to interpretation of the outcome.     

Periodontal disease in HIV/AIDS

Since the early 1990's, the death rate from AIDS among adults has declined in most developed countries, largely because of newer antiretroviral therapies and improved access to these therapies. In addition, from 2006 to 2011, the total number of new cases of HIV infection worldwide has declined somewhat and has remained relatively constant. Nevertheless, because of the large numbers of existing and new cases of HIV infection, the dental practitioner and other healthcare practitioners will still be required to treat oral and periodontal conditions unique to HIV/AIDS as well as conventional periodontal diseases in HIV-infected adults and children. The oral and periodontal conditions most closely associated with HIV infection include oral candidiasis, oral hairy leukoplakia, Kaposi's sarcoma, salivary gland diseases, oral warts, other oral viral infections, linear gingival erythema and necrotizing gingival and periodontal diseases. While the incidence and prevalence of these oral lesions and conditions appear to be declining, in part because of antiretroviral therapy, dental and healthcare practitioners will need to continue to diagnose and treat the more conventional periodontal diseases in these HIV-infected populations. Finding low-cost and easily accessible and acceptable diagnostic and treatment approaches for both the microbiological and the inflammatory aspects of periodontal diseases in these populations are of particular importance, as the systemic spread of the local microbiota and inflammatory products of periodontal diseases may have adverse effects on both the progression of HIV infection and the effectiveness of antiretroviral therapy approaches. Developing and assessing low-cost and accessible diagnostic and treatment approaches to periodontal diseases, particularly in developing countries, will require an internationally coordinated effort to design and conduct standardized clinical trials.     

Which periodontal changes are associated with HIV infection?

Abstract. To assess the validity of diagnostic criteria for HIV-associated periodontal diseases, existing sets of criteria were applied post-hoc to cross-sectional data of the periodontal health of men with and without HIV and their ability to predict HIV infection was compared. Criteria for gingival or periodontal ulceration predicted HIV infection to a similar level. Criteria sensitive to erythema of the attached gingiva and interdental craters had high positive predictive values. Distinct gingival red bands did not predict HIV. 3 HIV-associated periodontal changes were recognised: erythema of the attached gingiva; necrotizing periodontal disease and interdental craters. Epidemiological research should also consider conventional gingivitis and lost periodontal attachment. The presence or absence of all 5 conditions should be recorded at each site. Hierarchies of diagnoses with only the most severe condition assigned to each individual swamp valuable information.     

(A1) Identification of oral health care needs in children and adults, management of oral diseases

The workshop considered five questions reviewing the identification of international oral health care needs of children and adults, and the management of oral diseases in resource-poor countries: (1) What is the role of the dental profession in the management of the HIV-infected individual? (2) Identifying health care needs-What are the epidemiology and disparities of HIV-associated oral lesions in children from different continents? (3) How effective is HIV treatment in controlling oral diseases? (4) Could we develop basic inexpensive oral and dental care protocols for economically deprived HIV-infected patients? and (5) What is the best method of arranging resources to meet the oral health care needs of people with HIV disease? The consensus of the workshop participants was that there is a need to re-target research efforts to non-established market economy countries and prioritize research in these regions to children with HIV disease. It will be important to assess commonalities and variations in oral health needs across geographical and cultural boundaries, and research efforts should be centralized in resource-poor countries to support multi-center longitudinal standardized studies. It is essential that oral health research be integrated into other health care research programs, to make these research priorities and public health initiatives feasible.     

HIV infection and periodontal diseases: an overview of the post-HAART era

HIV infection remains a global health problem of unprecedented dimensions, although the development of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease into a manageable chronic disease with longer survival and improved quality of life in HIV-infected subjects. Among the HIV-associated infections, oral lesions have been recognized as prominent features since the beginning of the epidemic and continue to be important. Periodontal diseases strongly associated with HIV infection are classified as linear gingival erythema, necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis and are included among the cardinal oral lesions. Although oral candidiasis appears to be the infection more significantly decreased after the introduction of HAART, the current literature suggests that the prevalence and course of periodontal lesions have also been modified. Higher prevalence of opportunistic microorganisms has been frequently detected in the subgingival flora of HIV-infected individuals, probably due to the immune status of those patients, as colonization and overgrowth of atypical pathogenic species is facilitated by immunosuppression. Additional research is required regarding biological issues such as the role of oral immune factors and periodontal disease in the persistency of HIV infection, the possibility of oral transmission and the re-emerging of HIV infection.     

Periodontal health and HIV infection

Despite a large amount of research of periodontal health seen in HIV infection, much remains to be learned. Very few large controlled studies of infected people at settings not self-selected for oral disease have been reported, and few have investigated the necrotising periodontal diseases described in HIV infection. In this paper we present a brief review of three approaches to identify periodontal changes associated with HIV infection and identify possible aetiological factors for them. First, we summarise the methods and findings of a controlled blinded study of the periodontal health of homosexual men attending a genito-urinary medicine clinic. Second, we précis a case-control study of gingival ulceration among patients at a dedicated dental clinic. Finally, we outline how the validity of diagnostic criteria for HIV-associated periodontal changes were tested against the data collected in the controlled study.     

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.     

An update on HIV and periodontal disease

With the advent of newer pharmacological approaches to the treatment of human immunodeficiency virus (HIV) infection, the incidence and progression of both atypical and conventional periodontal diseases are changing. The incidence of necrotizing periodontitis and gingival diseases of fungal origin appears to be on the decline as a result of these therapies that have led to increased life spans for HIV patients. However, in cases where these therapies lose their effectiveness and HIV patients relapse into an immunosuppressed state, these conditions may recur. Recent evidence has shown that HIV patients with more conventional periodontal diseases such as chronic periodontitis may have increased attachment loss and gingival recession when compared to their HIV-negative counterparts. This pattern of loss of periodontal support may be due in part to a diffuse invasion of opportunistic bacterial infections, viruses, and fungi into the gingival tissue, leading to a more elevated and more diffuse destructive inflammatory response in the periodontal soft and hard tissues. While the accepted approaches to treating the spectrum of periodontal diseases in HIV patients remain essentially unchanged over the past 15 years, the impact of newer systemic therapies on patient immunocompetence may influence treatment decisions.     

The significance and management of periodontal lesions in HIV infection

It is now almost 20 years since we reported the existence of a previously unknown lesion, oral hairy leukoplakia, and its unexpected nature as the only human disease in which there is prolific replication of the gamma-herpesvirus, Epstein–Barr virus (EBV). Since then, it has become clear that, in the HIV-infected population, oral lesions are of particular significance. Their presence in individuals of unknown HIV serostatus is highly suggestive of HIV infection, while in people who are known to be HIV-infected, the development of oral candidiasis or hairy leukoplakia – often the very first lesions to occur – indicates that the battle between HIV virion production and destruction of immunologically important cells on, versus replacement of those cells has shifted in favour of HIV. These observations have led to the almost universal inclusion of oral lesions in staging and classification schemes for HIV infection. Recently, lower frequencies of oral disease have been seen in those on HIV therapy, except that oral warts may become more common as the viral load falls and CD4 count rises.
OBJECTIVES: To review the significance and management of periodontal lesions seen in HIV infection.
DESIGN: Traditional review.
RESULTS: HIV-associated periodontal lesions may be categorised as unusual forms of gingivitis, necrotizing periodontal diseases and exacerbated periodontitis. These lesions are significant in the extent to which they mark the underlying HIV disease and have service planning implications. Only limited data are available to inform guidelines for the management of individual patients.
CONCLUSIONS: Research of the effectiveness of interventions for HIV-associated periodontal lesions is needed.     

The severity, extent and recurrence of necrotizing periodontal disease in relation to HIV status and CD4+ T cell count

South Africa ranks among the three countries with the highest prevalence of HIV infection in sub-Saharan Africa, with an estimated 29.5% of women attending antenatal clinics being infected. Necrotizing periodontal disease is a well recognized HIV-associated oral condition. The objective of this investigation was to determine a possible correlation between the extent, severity and treatment outcome of necrotizing periodontal disease in relation to a person's HIV status and CD4+ T cell count. Data from 105 consecutive patients presenting with necrotizing periodontal disease at an academic oral health centre in South Africa were analysed. All patients were provided with an opportunity to undergo voluntary counseling and testing for HIV infection, were treated for necrotizing periodontal disease and followed over a period of nine months. The mean age of the cohort was 28 years old (range 12 - 52). Of 98 (93.3%) patients unaware of their HIV serostatus at the initial visit, 59 (56.2%) consented to testing. In total 45 (42.9%) were HIV-seropositive with a mean CD4+ T cell count of 222.7 cells/microl and 14 (13.3%) were HIV-seronegative, with a significantly higher mean CD4+ T cell count of 830 cells/microl (Fisher's exact test, p < 0.001), while the status of 46 (43.8%) remained unknown. In 101 (96.2%) patients, > or = 5 tooth sites were affected, and in 27 (26%) > or = 4 mm of gingival tissue were affected. This study, which included HIV-seropositive, HIV-seronegative and persons of unknown HIV status, revealed no statistical evidence that HIV infection was associated with the extent, severity or relapse of necrotizing periodontal disease. No statistically significant association could be demonstrated between the extent, severity and recurrence of necrotizing periodontal disease and a CD4+ T cell count < or = 200 cells/microl among HIV-seropositive patients.     

Viruses in periodontal disease - a review

The purpose of this review was to evaluate the evidence supporting the hypothesis that viral infection plays a role in the development of periodontitis. An involvement in periodontal diseases has been suspected specifically for human immunodeficiency virus (HIV) and herpes viruses. An association has been demonstrated between HIV infection and some distinct forms of periodontal infection, i.e. necrotizing lesions. Furthermore, reports of increased prevalence and severity of chronic periodontitis in HIV-positive subjects suggests that HIV infection predispose to chronic periodontitis. Several studies, most of them from the same research group, have demonstrated an association of herpesviruses with periodontal disease. Viral DNA have been detected in gingival tissue, gingival cervicular fluid (GCF) and subgingival plaque from periodontaly diseased sites. In addition markers of herpesviral activation have been demonstrated in the GCF from periodontal lesions. Active human cytomegalovirus (HCMV) replication in periodontal sites may suggest that HCMV re-activation triggers periodontal disease activity. Concerns regarding sampling, methods and interpretation cast doubts on the role of viruses as causes of periodontal disease.     

Diabetes mellitus and periodontal diseases

BACKGROUND: The purpose of this review is to provide the reader with practical knowledge concerning the relationship between diabetes mellitus and periodontal diseases. Over 200 articles have been published in the English literature over the past 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of diabetes and periodontitis and different clinical criteria applied to prevalence, extent, and severity of periodontal diseases, levels of glycemic control, and complications associated with diabetes. METHODS: This article provides a broad overview of the predominant findings from research published in English over the past 20 years, with reference to certain "classic" articles published prior to that time. RESULTS: This article describes current diagnostic and classification criteria for diabetes and answers the following questions: 1) Does diabetes affect the risk of periodontitis, and does the level of metabolic control of diabetes have an impact on this relationship? 2) Do periodontal diseases affect the pathophysiology of diabetes mellitus or the metabolic control of diabetes? 3) What are the mechanisms by which these two diseases interrelate? and 4) How do people with diabetes and periodontal disease respond to periodontal treatment? CONCLUSIONS: Diabetes increases the risk of periodontal diseases, and biologically plausible mechanisms have been demonstrated in abundance. Less clear is the impact of periodontal diseases on glycemic control of diabetes and the mechanisms through which this occurs. Inflammatory periodontal diseases may increase insulin resistance in a way similar to obesity, thereby aggravating glycemic control. Further research is needed to clarify this aspect of the relationship between periodontal diseases and diabetes.     

HIV- periodontal disease. A review of research prospects: a South African and Namibian perspective.

In the course of infection by the human immunodeficiency virus (HIV) typical changes of inflammatory periodontal disease may arise. It is estimated that the prevalence of HIV-associated periodontal diseases may vary between 5% and 12% and can occur in both symptomatic and asymptomatic individuals. These oral lesions are very important either as an initial presentation of AIDS or as a sign of established immunosuppression. For the patients, HIV-associated periodontal diseases can cause pain, severe discomfort and a decreased quality of life. It is therefore important, from both diagnostic and therapeutic aspects, for dentists to be able to distinguish and diagnose HIV-associated periodontal diseases as early recognition and treatment of these oral lesions may reduce morbidity and allow more comfort to the patient during progression of the disease. This paper reviews the current international and regional status of HIV-associated periodontal diseases and highlights research prospects in countries such as Namibia and South Africa, to further analyse periodontal diseases in HIV/AIDS patients.     

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.     

Periodontal disease associated with HIV infection.

Patients with severe immunosuppression as a consequence of infection by human immunodeficiency virus (HIV) are at risk for a number of severe periodontal diseases. HIV-associated gingivitis and HIV-associated periodontitis (HIV-P) are seen exclusively in HIV-infected persons. In some cases HIV-P may extend into adjacent soft tissue and bone, resulting in necrotizing stomatitis of periodontal origin. In addition, acute necrotizing ulcerative gingivitis has also been reported to have an increased prevalence in HIV-infected patients. The clinical and microbiologic features of HIV-associated gingivitis and HIV-P suggest that these diseases are early and later stages of the same lesion, that results in severe gingival erythema, extensive soft tissue necrosis, and destruction of alveolar bone. Although acute necrotizing gingivitis and the initial stages of HIV-P share a number of clinical signs current evidence indicates that they are distinct pathologic processes. Treatment of these lesions requires debridement, local antimicrobial therapy, immediate follow-up care, and long-term maintenance. In addition, patients with systemic involvement or extensive and rapidly progressing lesions may require systemic antibiotics appropriate to the organisms that dominate the lesion.     

Necrotizing ulcerative periodontitis

In patients with no known systemic disease or immune dysfunction, necrotizing periodontitis (NUP) appears to share many of the clinical and etiologic characteristics of necrotizing ulcerative gingivitis (NUG) except that patients with NUP demonstrate loss of clinical attachment and alveolar bone at affected sites. In these patients, NUP may be a sequela of a single or multiple episodes of NUG or may be the result of the occurrence of necrotizing disease at a previously periodontitis-affected site. The existence of immune dysfunction may predispose patients to NUG and NUP, especially when associated with an infection of microorganisms frequently associated with periodontal disease such as Treponema and Selenomonas species, Fuscobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. The role of immune dysfunction is exemplified by the occasionally aggressive nature of necrotic forms of periodontal disease seen in patients with HIV infection or malnutrition, both of which may impact host defenses. Clinical studies of HIV-infected patients have shown that patients with NUP are 20.8 times more likely to have CD4+ cell counts below 200 cells/mm3. However, these same studies have demonstrated that most patients with CD4+ cell counts below 200 cells/mm do not have NUP, suggesting that other factors, in addition to immunocompromisation, are involved. Further studies are needed to define the complex interactions between the microbial, or viral, etiology of necrotic lesions and the immunocompromised host. It is, therefore, recommended that NUG and NUP be classified together under the grouping of necrotizing periodontal diseases based on their clinical characteristics.     

Urban legends series: oral manifestations of HIV infection

Human immunodeficiency virus‐related oral lesions (HIV‐OLs), such as oral candidiasis (OC) and oral hairy leukoplakia (OHL), have been recognized as indicators of immune suppression since the beginning of the global HIV epidemic. The diagnosis and management of HIV disease and spectrum of opportunistic infection has changed over the past 30 years as our understanding of the infection has evolved. We investigated the following controversial topics: (i) Are oral manifestations of HIV still relevant after the introduction of highly active antiretroviral therapy (HAART)? (ii) Can we nowadays still diagnose HIV infection through oral lesions? (iii) Is the actual classification of oral manifestations of HIV adequate or does it need to be reviewed and updated? (iv) Is there any novelty in the treatment of oral manifestations of HIV infection? Results from extensive literature review suggested the following: (i) While HAART has resulted in significant reductions in HIV‐OLs, many are still seen in patients with HIV infection, with OC remaining the most common lesion. While the relationship between oral warts and the immune reconstitution inflammatory syndrome is less clear, the malignant potential of oral human papillomavirus infection is gaining increasing attention. (ii) Effective antiretroviral therapy has transformed HIV from a fatal illness to a chronic manageable condition and as a result expanded screening policies for HIV are being advocated both in developed and in developing countries. Affordable, reliable, and easy‐to‐use diagnostic techniques have been recently introduced likely restricting the importance of HIV‐OLs in diagnosis. (iii) The 1993 EC‐Clearinghouse classification of HIV‐OLs is still globally used despite controversy on the relevance of periodontal diseases today. HIV‐OL case definitions were updated in 2009 to facilitate the accuracy of HIV‐OL diagnoses by non‐dental healthcare workers in large‐scale epidemiologic studies and clinical trials. (iv) Research over the last 6 years on novel modalities for the treatment of HIV‐OLs has been reported for OC and OHL.     

Periodontal diseases in HIV-infected patients

Abstract Periodontal diseases may be the first clinical sign of human immunodeficiency virus (HIV)-infection. Since the immunosuppression and subsequent susceptibility may alter the responses of the oral tissues as well as the microflora, both periodontal treatment and result of therapy may be modified. The periodontal diseases in HIV-seropositive patients include common as well as less conventional forms of gingivitis and periodontitis, and bacteria, mycotic and viral infections are seen. Neoplasias may also involve the periodontium; most common are Kaposi's sarcoma and non-Hodgkin's lymphoma. Recent studies of unselected groups of patients indicate that periodontal health in at least some groups of HIV-seropositive patients is better than previously reported.     

Changing periodontal concepts: treatment considerations

Many clinical trials conducted during the last decade have clarified controversial issues and resulted in changed periodontal paradigms. These modified concepts have therapeutic implications. Some salient altered periodontal concepts include the following: The mere presence of pathogens will not initiate periodontal diseases. Most subgingival bacteria reside in biofilms. Periodontal diseases are infections. Periodontal pathogens can be transferred between family members. The host response can be protective and destructive. Gingivitis does not usually proceed to periodontitis. Risk factors in conjunction with bacteria and the host response can affect the severity of disease, patterns of destruction, and the response to therapy. Many medical conditions (eg, diabetes, smoking, and HIV infection) may predispose patients to periodontitis. Associations between periodontitis and a number of systemic ailments (eg, diabetes, adverse pregnancy outcomes, and cardiovascular disease) have been detected and are being investigated to determine if there is a cause-and-effect relationship. Diagnostic and therapeutic implications of these altered paradigms are addressed throughout the article.     

Oral research and dental treatment in HIV infection.

In June 1991, practicing, research, and academic dentists attended a symposium on oral research and dental treatment in HIV infection at Guy's Hospital in London, England. Oral lesions in HIV infection were classified as strongly associated, probably associated, and possibly associated with HIV infection. A speaker stressed that those strongly associated with HIV infection should be of the most interest to general dental practitioners. Another speaker said that chronic erythematous candidiasis has emerged as an oral infection strongly associated with HIV infection in addition to pseudomembranous candidiasis. A dentist mentioned hairy leukoplakia as a new condition strongly associated with HIV infection. Other HIV associated periodontal disease included gingivitis, necrotizing gingivitis, and periodontitis. A speaker noted that AZT increases longevity of AIDS patients and the drugs dideoxyinosine and dideooxycytidine are being tested. Another dentist spoke about the issue of HIV infected dentists citing the example of the dentist in Florida who infected 5 patients. Other speakers addressed the cases and needs of asymptomatic HIV infected people. A survey of dentists showed that only 33% of dentists would provide dental care to HIV infected people and only 20% would if the patients had AIDS. A dentist addressed the problem of a lack of data on prevention and treatment of oral lesions since their etiology and pathogenesis were unknown. Other presentations focused on research on antibodies and DNA probes in reference to saliva and subgingival flora. The symposium revealed the ran ge and depth of research going on in British schools on oral manifestations of HIV infection.