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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.

Objective To review the existing research literature on the paradigm that the oral lesions could be an indicator of the disease severity with the objective of documenting the current status of research, highlighting its major findings. Material and methods Publications were identified through a careful search, of which a majority focused on oral lesions as an indicator for HIV progression. A PubMed journal search of 10 years OF period publication (2009-2019) for "oral lesion, oral manifestation, indicator, HIV and HIV-associated" was performed and analysed. Various research methods were included within the study criteria including clinical study, clinical trial, comparative study and randomised control trial. Results A total 33 studies were obtained and analysed, including cohort study, cross-sectional study, case-control study, clinical trial, retrospective observational analysis study, prospective observational study and randomised control trial. The most common oral lesions found in the studies were Kaposi sarcoma (KS), followed by oral candidiasis, periodontitis, necrotising ulcerative gingivitis (NUG), necrotising ulcerative periodontitis (NUP) and oral hairy leucoplakia (OHL). The early diagnosis and accurate treatment plan were very important to indicate the disease severity related to HIV infection. Conclusion Oral lesions reported in 39% articles and could be an indicator of HIV disease severity due to its effects on decreased cluster-differentiated (CD4+) T-cell count and increased viral load.

Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus that establishes a lifelong persistent infection in the oral cavity and is intermittently shed in the saliva. EBV exhibits a biphasic life cycle, supported by its dual tropism for B lymphocytes and epithelial cells, which allows the virus to be transmitted within oral lymphoid tissues. While infection is often benign, EBV is associated with a number of lymphomas and carcinomas that arise in the oral cavity and at other anatomical sites. Incomplete association of EBV in cancer has questioned if EBV is merely a passenger or a driver of the tumorigenic process. However, the ability of EBV to immortalize B cells and its prevalence in a subset of cancers has implicated EBV as a carcinogenic cofactor in cellular contexts where the viral life cycle is altered. In many cases, EBV likely acts as an agent of tumor progression rather than tumor initiation, conferring malignant phenotypes observed in EBV-positive cancers. Given that the oral cavity serves as the main site of EBV residence and transmission, here we review the prevalence of EBV in oral malignancies and the mechanisms by which EBV acts as an agent of tumor progression.

Well into the fourth decade of the HIV/AIDS pandemic, we can look back on the early years, the initial discoveries, and the broad sweep of the progress of our understanding of the nature, causes, and significance of the oral lesions seen in those infected with the virus. Prominent among these is oral hairy leukoplakia (HL), a previously unknown lesion of the mouth associated with Epstein-Barr virus (EBV) and initially seen only in people with AIDS, in the then-recognized risk groups, or those shown to be HIV positive. Subsequently, it became clear that the distribution of HL extends well beyond the HIV spectrum. In this brief review, we consider the clinical and histological features of HL, discuss how it was discovered, explore its cause, diagnosis, relationship with AIDS, pathogenesis, significance in EBV biology, options for management, and how it changes with HIV/AIDS therapy.

OBJECTIVE: Oral hairy leukoplakia (OHL) is a white lesion of the tongue that is caused by Epstein-Barr virus (EBV) and occurs mainly in people infected with human immunodeficiency virus (HIV). The aim of this study was to determine whether the presence of OHL reflects the absence of EBV-specific cytotoxic T lymphocyte (CTL) activity. SUBJECTS AND METHODS: EBV-specific CTL responses were measured in HIV-positive homosexual men with OHL, HIV-positive homosexual men without OHL, and HIV-negative homosexual men. Also, the phenotypes of cells responsible for EBV-specific responses were studied. RESULTS: Eighty percent (8/10) of HIV-positive subjects with OHL, 52% (12/23) of HIV-positive subjects without OHL, and 83% (15/18) HIV-negative subjects had a positive anti-EBV CTL response (P= 0.004, Kruskal-Wallis test). Two HIV-positive subjects showed a greater anti-EBV CTL response after developing OHL than before the appearance of OHL. Additional experiments showed that CD8-positive T cells and CD4-positive T cells were responsible for the EBV-specific CTL responses. CONCLUSION: Our data show more EBV-specific CTL activities in HIV-positive individuals with OHL than in HIV-positive individuals without OHL. Whether the presence of EBV-specific CTL contributes to resolution of OHL remains to be clarified.

OBJECTIVE To test the hypothesis that the anti-apop totic ability of Epstein-Barr virus (EBV) may result in altered expression of apoptosis-associated proteins in oral hairy leukoplakia (HL), we evaluated HL tissue and normal epithelium for these proteins by immunohistochemistry. MATERIALS AND METHODS Twenty formalin-fixed, paraffin-embedded specimens of HL lesions and six spedmens of normal control mucosa were selected from archived tissue specimens. Bcl-2. Bcl-x, Bax and p53 apoptoris-associated proteins were evaluated in immu-nohistochemically stained tissue sections according to staining intensity and pattern. The percentage of p53-positive burl cells was estimated in sequential fields. RESULTS: Generalty, there were only slight differences in the expression of Bcl-2 and Bcl-x proteins in the epithelium of HL and control tissue. The staining for Bcl-2 was weaker in keratinocytes than in putative melano-cytes and Langerhans cells. Equivocal diffuse cytoplasmic staining of prickle cells was also noted. Keratinocytes throughout the epithelium stained positively for Bcl-x protein, although upper layers were more weakly stained. The ‘balloon’ keratinocytes in HL were infrequently positive for Bcl-x. Bax staining in HL differed from that in control tissue in being more heterogeneous. The staining reaction in HL was weak to negative in upper epithelial levels where ‘balloon’ keratinocytes were located. Weak to moderate nuclear p53 protein staining was detected in a mean of 25.3% of basal keratinocytes in all but one of the HL specimens; weak staining was seen in only two control specimens. CONCLUSIONS: We found only slight immunohistochemid evidence that expression of the apoptosis-associated proteins is altered in HL. p53 appears to be over-expressed in HL; we speculate that this may be related to upregulation or stabilization of wild-type p53 protein related to EBV infedon.

OBJECTIVES: Examine variations in oral manifestations of HIV by gender, race, risk behaviors, substance use and immune status in a previously unstudied population in the southeast region of the USA. DESIGN: Cross-sectional analytic study. SETTING: Academic medical center, North Carolina, USA. SUBJECTS: First 238 HIV-infected adults (76% male; 59% Black) enrolled in an ongoing longitudinal study. METHODS: Oral examination, medical chart review, sociodemographic and behavioral interview. Descriptive, bivariate, and multivariable analyses. OUTCOMES: Presence of oral manifestations of HIV. RESULTS: 50% had recent CD4 counts

OBJECTIVE: This report evaluates and compares individual oral lesions and combinations of lesions in predicting progression-free survival in a seroprevalent cohort of men and women with HIV infection. DESIGN: This was a prospective study of HIV-infected patients, initially AIDS-free, followed for approximately 30 months. SETTING: Patients were volunteers examined at an academic medical center and at an inner-city hospital in New York. Participants identified themselves as homosexual men or as injection drug users (IDU). OUTCOME MEASURES: The primary outcome being assessed is time from a baseline oral examination until the development of an AIDS-defining condition or death from any cause within 12 months of the last study visit. Correlation is measured by relative risk (RR). RESULTS: While oral lesions were not predictive of progression among subjects with CD4 > or = 200, they were highly predictive of progression among those with CD4 < 200. For subjects with CD4 < 200, the only individual lesion that was significantly associated with progression-free survival was oral candidiasis (RR = 4.12, P = 0.009). Positivity for one or more lesions in a set demonstrated greater prognostic value among those with CD4 < 200, with RR's of 6.03 (P = 0.018) for the set consisting of oral candidiasis, hairy leukoplakia, and necrotizing ulcerative gingivitis (NUG), and 8.77 (P = 0.036) for the set consisting of the above lesions plus linear gingival erythema (LGE). Analysis by cohort suggested that the improvement in correlation was stronger in homosexual men than in IDU, but this question could not be resolved conclusively with these data. CONCLUSIONS: Lesion sets might be better prognosticators of progression-free survival than individual lesions among HIV-infected subjects with CD4 < 200. Prognostic value of the core lesion set (oral candidiasis and hairy leukoplakia) was enhanced by the addition of other lesions (NUG and LGE) not usually included in HIV staging systems. These results suggest that staging systems for HIV might be improved by the inclusion of other, survival-related oral lesions.

The first case of oral hairy leukoplakia (OHL) in an HIV-negative 56-year-old patient with acute lymphocytic leukemia (ALL) is reported. A white plaque was observed while the patient was in complete remission which followed the chemotherapeutic scheme. The clinical and histopathologic findings were typical for OHL and the polymerase chain reaction method was positive for Epstein-Barr virus DNA. Underdiagnosis and underreporting of OHL in patients with a malignant haematological disease and the apparent different environmental factors to which these non-AIDS patients have been exposed, probably constitute some of the reasons for the very few OHL cases reported in these patients.

Objective: The purpose of this study was to determine the prevalence of the oral manifestations of HIV/AIDS and to correlate the prevalence of these lesions with the stages of the disease in the Ife-Ijesa zone, Nigeria. No comprehensive data were available for correlating it with the staging of HIV/AIDS in this region. Subjects: The pattern of oral HIV lesions as classified by the EC-Clearinghouse was studied in 225 confirmed consecutive HIV-infected patients in this zone. Methods: Clinical dental examinations were conducted under natural daylight on all consenting HIV patients, sitting in an upright chair, using dental mirrors and probes. Results: The prevalence of oral HIV lesions was 84.0%, with lesions ranging in number from one to six. The commonest HIV lesion was pseudo-membranous candidiasis (43.1%) followed by erythematous candidiasis (28.9%), angular cheilitis (28.9%), linear gingival erythema (24.0%) and ulcerations (8.9%). Lesions less commonly found were oral hairy leukoplakia (1.3%) and salivary gland swellings (1.3%). Heterosexual intercourse was the most common mode of transmission (94.7%) and HIV-1 (96.9%) the most prevalent pathogen among the study population. The majority of the patients were in the WHO clinical stage III (59.1%) and presented late. Conclusions: The prevalence of oral HIV lesions in the present study was high.

Introduction: Oral candidosis (OC) and hairy leukoplakia (OHL) are important markers of Human Immunodeficiency Virus (HIV) infection immune status. Objectives: to evaluate if OC and/or OHL should be considered clinical predictors of immune and virologic failure on HIV-infected Brazilian adults undergoing Highly Active Antiretroviral Therapy (HAART). Methods: 124 HIV-infected patients who used HAART for a minimum of six months were prospectively evaluated. All of them under-took oral examination and serum CD4+ count and viral load (VL), being divided in two groups, P and A, respectively according to the presence or absence of OC and/or OHL. During a six month period, patients belonging to group A were followed. They were re-examined for new oral lesions. New blood samples were collected and they were subdivided into groups P6 and A6. CD4+ count and VL were compared between groups at baseline and after the six months period. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and relative risk (RR) were obtained in order to assess the accuracy of using OC and OHL as predictors of immune and virologic failure, at baseline and after a six month period. Results: At baseline and after six months, patients with OC and OHL have mean CD4+ count lower and mean VL higher than patients of group A and A6 (p

A large number of studies attest to the frequency of oral disease in those with HIV infection. Most show that hairy leukoplakia and pseudomembranous candidiasis are the commonest lesions in those with HIV infection and AIDS, with higher prevalence and incidence rates correlating with falling CD4 counts and disease progression. HIV-infected individuals with oral candidiasis or hairy leukoplakia progress to AIDS more rapidly than matched controls without these lesions. Oral candidiasis and hairy leukoplakia increase with time since seroconversion. On the other hand, parotid enlargement in children appears to be associated with slower progression to AIDS. As a consequence of these and other observations, oral lesions are widely included in natural history studies, staging and classification schemes for HIV infection. In addition to their role in the diagnosis of HIV infection and as indicators of the progression of HIV disease, oral lesions are used as clinical correlates of CD4 counts and as criteria for entry into clinical trials.

Hairy leukoplakia (HL) is a lesion found on the side of the tongue of immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection. The lesion has unique histopathologic features and is characterised by high-level Epstein-Barr virus (EBV) replication, multiple EBV strains, and extensive inter- and intra-strain recombination. Expression of EBV genes spanning the entire viral life cycle from latency-associated genes to late, replicative genes has been detected in the lesion. HL thus provides a unique opportunity to study EBV expression in oral epithelium, and to study expression of novel EBV genes. We therefore constructed a cDNA library from an HL biopsy and detected expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs revealed few amino acid changes from the B95-8 sequence. Expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer. BDLF-3 protein expression was observed in the peri-nuclear space and Golgi compartment. The function of these proteins is currently under investigation.

OBJECTIVE: The prevalence of Epstein-Barr virus (EBV) and the recently discovered Kaposi's sarcoma associated herpes virus, human herpesvirus 8 (KSHV or HHV8), was determined within oral lesions common to HIV infection including OHL, pseudoOHL (PHL), oral lymphoma, oral aphthous ulcers, and an oral Kaposi's sarcoma. METHODS: DNA and RNA were extracted from oral lesions. EBV and HHV8 genomes were detected by Southern blot and polymerase chain reaction (PCR), and viral expression was analyzed using PCR amplification of cDNA. RESULTS: Multiple EBV strains were detected within OHL with recombination across repeat sequences generating new viral variants. EBV expression in OHL included expression of some viral genes, usually expressed in latent infections, that induce the EBV receptor. EBV replication was detected only within OHL lesions but not within adjacent Kaposi's tissue or oral aphthous ulcers while HHV8 was only detected within the Kaposi's lesions. CONCLUSIONS: These findings indicate that the OHL lesion is unique with viral replication and superinfection with additional EBV strains. Expression of the EBV receptor within the OHL lesion may promote superinfection which then activates EBV replication. The consistent detection of EBV replication only within OHL lesions and the detection of HHV8 only within Kaposi's sarcoma, strengthens the etiologic link between EBV and HHV8 infection to these specific pathologies.

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.

Objectives: To assess types and prevalence of HIV-related oral lesions among HIV-infected individuals in south India and to correlate common oral findings with co-morbidities, gender, age and medication. Subjects and methods: One hundred and one patients with HIV infection or AIDS at infectious diseases units of Attavar Hospital, Mangalore, and medical wards of Kasturba Medical College, Manipal, were selected. Sociodemographic information was obtained using a structured questionnaire. Oral lesions were diagnosed according to the presumptive criteria of EEC-Clearinghouse Classification. Clinical history was retrieved from patient's medical records. Results: Erythematous candidiasis (44.5%), melanotic hyperpigmentaion (34.6%) and xerostomia (29.7%) were among the most common oral manifestations. A significant association was found between oral candidiasis and advanced immunosuppression (P

OBJECTIVES: A multicentre collaborative study by the London HIV and Dentistry Group failed to associate the presence of erythematous candidiasis (EC) with advanced HIV disease. Data from a study of the periodontal health of homosexual men attending a genito-urinary medicine clinic presented an opportunity to investigate social and medical factors related to the presence of EC and mucosal disease. SUBJECTS AND METHODS: 312 men with HIV were examined by a single examiner blinded to HIV status; 22.8% had an indicator condition for AIDS; 37.8% had CD4 lymphocyte counts less than 200 cells mm−3; and 53.8% met the 1993 case definition for AIDS; 59.6% of the men with HIV had oral manifestations of the infection. The most common were: oral hairy leukoplakia, 44.2%; EC, 26.9%; and pseudomembranous candidiasis (PC), 11.5%. RESULTS: Advanced HIV disease was a less powerful predictor of EC than PC. Advanced HIV disease also predicted the presence of hairy leukoplakia and mucosal ulceration. EC was strongly associated with tobacco use. CONCLUSIONS: While methodological differences explain some variation with previous research, these data also suggest that EC and PC may not carry the same prognostic significance and longitudinal studies are required to confirm these findings.

Opportunistic DNA viruses, particularly members of the herpesvirus family, are frequently the aetiological agents of HIV-associated oral lesions. Oral lesions common to the early phase of the AIDS epidemic, including Kaposi's sarcoma (KS), oral aphthous ulceration, AIDS-associated oral lymphoma, and oral hairy leukoplakia (OHL), have been tested for the prevalence of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). While EBV DNA is detected by PCR in all of these lesions, abundant viral replication can only be detected in OHL. In OHL, a novel state of EBV infection has been discovered with concurrent expression of replicative and transforming proteins, with all of these proteins contributing to the development of the lesion. Activation of signalling pathways and up-regulation of the viral receptor, proliferative and antiapoptotic genes by these proteins induce several of the histological features common to OHL, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of EBV transforming proteins within the permissively infected OHL tissue enables epithelial cell survival and may enhance viral replication. Detection of KSHV in these HIV-infected individuals has been localized only to their saliva. Replicative and latent KSHV gene products have been detected in association with the development of oral KS lesions. EBV, but not human cytomegalovirus (HCMV), has been detected by PCR in minor salivary gland biopsies of HIV-associated salivary gland disease. Human papillomaviruses (HPV) are associated with oral warts in HIV-positive individuals; a diagnosis that appears to be increasing in frequency in the era of highly active antiretroviral therapy. To date, there appears to be little increase in the incidence of HPV-associated oral cancer. The mechanisms of interaction between HIV and HPV are not fully understood. Expression of viral gene products is clearly important and necessary for the development of multiple AIDS-associated oral lesions.

Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein-Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via nonglossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis.

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.

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.To review the significance and management of periodontal lesions seen in HIV infection.Traditional review.HIV-associated periodontal lesions may be categorized 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.Research of the effectiveness of interventions for HIV-associated periodontal lesions is needed.

The workshop agreed that the development of consensus quantification protocols was desirable, but that this whole field was underdeveloped, to date. The working goals were therefore redefined (vide infra). Three possible protocols were presented and discussed relating to oral hairy leukoplakia, oral ulceration (NOS) and oral candidiasis. There was agreement that different data-set protocols would have to be developed for specific HIV-related mucosal diseases. Furthermore, the data set should be consistent, standardized and disaggregated. In this way, with everyone working to the same standards of outcome, data from geographically, nationally, socially or culturally different areas could be readily compared. A future meeting to generate the disease-specific protocols would, most likely, be needed.

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.

An International Workshop addressed the prevalence and classification of HIV/ AIDS associated oral lesions.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?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.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.

To investigate changes in the prevalence of mucosal disease in patients with HIV/AIDS.Retrospective analysis of clinic database.An open-access dental clinic dedicated to the dental treatment of patients infected with HIV in London, UK.Dental patients attending for routine assessment (check-up).Prevalence of HIV associated oral lesions, diagnosed in accordance with EC classification criteria, in patients taking and not taking antiretroviral therapies (ARTs).Data were collected at 2789 dental examinations for 1590 patients between 1992 and 1998. More patients taking ART had one or more oral manifestations in the years up to 1996, after which the prevalence fell to a similar level to those not taking medications. The prevalence of mucosal disease in patients not taking ART was relatively constant over time. These trends were observed for oral hairy leukoplakia, pseudomembranous and erythematous candidiasis and Kaposi's sarcoma but not for oral papillomata.These data provide evidence that decreases in the prevalence of oral disease in people with HIV infection can be attributed to the effectiveness of ART.

To determine the prevalence of EBV-DNA, CMV-DNA and HPV-DNA in oral healthy mucosa of HIV-infected and renal transplant patients. To associate the detection of viral genomes with laboratory parameters of immunodeficiency, gender, antiretroviral and immunosuppressive therapy.A cross-sectional analysis of lingual and buccal cytobrushings from HIV-infected and renal transplant patients.Lingual and buccal cytobrushings were obtained from clinically normal oral mucosa of 57 HIV+, 40 renal transplant patients and 30 healthy uninfected controls, all matched for age at baseline of examination. Presence of EBV-, CMV- and HPV-DNA was assessed by polymerase chain reaction (PCR). We evaluated their association, in HIV+ subjects, with gender, CD4+ cell count, HIV-RNA load, and antiretroviral therapy; and in renal transplant patients, with gender, CD4/CD8 ratio, and immunosuppressive therapy. Data were managed and analysed by Epi-Info 6.0.EBV-DNA was detected in 42.1% of HIV+ (24/57), in 65.0% of transplant patients (26/40), and in 16.6% of controls (5/30) (P = 0.03 and P = 0.0001, respectively). Furthermore, male gender in HIV+ group was found to be significantly associated with the presence of EBV-DNA (P = 0.02) vs females, after adjusting for CD4+ cell count and HIV-RNA load. CMV- and HPV-DNA were detected in 3.5% and 7.0% of HIV+, and in none and 20.0% of transplant patients, respectively. No relationship was found between the epithelial detection of these two viruses and any parameter evaluated.EBV genome was significantly detected in clinically normal oral mucosa of renal transplant and HIV+ patients. A significant gender association was found among HIV+, suggesting that oral hairy leukoplakia (OHL) is more likely to occur in HIV+ men than women.

OBJECTIVE: To describe the expression of integrins in the epithelium of oral hairy leukoplakia (HL) and compare to that of normal lateral tongue epithelium. MATERIALS AND METHODS: Immunohistochemistry to identify integrins (alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1) was performed, using a standard biotin-streptavidin-peroxidase technique on five clinically and histologically confirmed frozen biopsy specimens of HL and five normal lateral tongue control tissues. RESULTS: Expression of integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 was seen both in HL epithelium and in normal control tissue. alpha 5 expression was not seen in HL or in control tissue epithelium. alpha 2 and alpha 3 were expressed mainly in the basal and suprabasal layers; alpha 6 expression was most intense on the basal surface of the basal cells, alpha v was expressed in the basal and suprabasal layers with more expression seen in the higher differentiated cell layers than the other integrins. beta 1 expression was seen in the basal and suprabasal layers only. No apparent difference between HL and normal oral mucosa was noted in the staining pattern of the various integrins. CONCLUSION: Integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 are expressed in HL and the expression pattern is not different from that of normal oral mucosa. alpha 5 is not expressed in HL or in normal oral epithelium.

The past 2 decades have witnessed a profound transformation in the challenges facing the world with regard to HIV/AIDS infection. This fatal disease, though amenable to preventative measures, is now the fourth most common cause of death (UNAIDS/WHO, 1998). Globally, some 47 million people are HIV positive with 90% of these infections found in developing countries (Guthua et al, 1995). By the end of 1998, 33.4 million African children and adults were estimated to be living with HIV/AIDS. Sub-Saharan Africa is home to 67% (22.5 million) of these, even though only one-tenth of the world’s population resides there (UNAIDS/WHO, 1998). The spread of HIV in developing countries as indicated by reports from Africa, India and Thailand (UNAIDS/ WHO, 1998) is an issue of great concern. This is because most of the infected individuals are representative of the economically and reproductively active group within their communities. This will have a devastating effect on the socio-economic status of these already resource-poor countries—and the situation is made worse because of limited access to treatment with anti-HIV drugs. The purpose of this editorial is to draw attention to differences or similarities, if any, between the oral manifestations associated with HIV infection and AIDS (oral HIV/AIDS) in developing and developed countries. The association between tuberculosis (TB) and HIV has already been reported in the developing world (India, Vietnam, Philippines and Africa), but is less prevalent in the West (O’Keefe and Wood, 1996). Sub-Saharan Africa is where 6.6 million of the 9.4 million individuals who have HIV and TB are to be found. Malnutrition and nutritional deficiencies, especially protein energy malnutrition (Enwonwu, 1992) is rife amongst these populations in particular and is thought to be contributory to the oral and systemic complications of HIV infection. In Europe and North

OBJECTIVE: It has been observed that the cytopathic changes in hairy leukoplakia (HL) correlate with ultra-structural evidence of intra-keratinocyte herpes-type viral particles. In situ hybridization is considered to be the definitive confirmation of Epstein-Barr virus (EBV)-induced HL. This study evaluated the consistency of histopathological findings, which many believe to be diagnostic, with in situ hybridization for EBV-DNA in 60 patients with lesions clinically suggestive of HL. MATERIALS AND METHODS: Hematoxylin and eosin (H&E)-stained sections were reviewed independently by three oral pathologists who did not know the hybridization results. The presence in keratinocytes of nuclear inclusions and/or homogenization, believed to be specific for EBV in these lesions, was used as an indicator for infection. Cytoplasmic changes were evaluated separately. RESULTS: With in situ hybridization, 48 cases were positive and 12 were negative. When the two methods were compared, pathologist concurrence ranged from 83% to 92%. False negatives ranged from 6% to 19%, and false positives ranged from 8% to 25%. Cytoplasmic ballooning, homogenization, and perinuclear clearing were evident in all cases of hybridization-confirmed HL; however, these changes were also noted in 75% (9/12) of the cases with negative hybridization results. Most confirmed HL cases exhibited both nuclear homogenization and inclusions, although the former was more consistently seen. CONCLUSION: Cytoplasmic changes did not agree well with EBV-DNA hybridization results, whereas nuclear changes demonstrated good, but not complete, agreement. In appropriate clinical settings, the finding of nuclear inclusions and/or homogenization may be of diagnostic value. However, because the potential for false positives and negatives is high, H&E cytopathology should not be used as a substitute for in situ hybridization in the definitive diagnosis of oral hairy leukoplakia.

OBJECTIVES: Oral hairy leukoplakia (HL) is an acan-thotic, hyperparakeratotic lesion characterised by the presence of a replicative Epstein-Barr virus (EBV) infection in the superficial and adjoining layers of the epithelium. EBV or its gene products are capable of modifying epithelial differentiation. The aim of this study was to establish whether the presence of EBV was associated with an alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation and Ki 67 expression in lesional tissue and control mucosa. METHODS: Biopsies of HL together with age, site and sex matched controls (n= 7 and 8 respectively) were incubated in 200 μM BrdU in vitro, fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 fim sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length. RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence'of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication. CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection.

OBJECTIVES: Mucocutaneous diseases are common in patients infected with human immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV-infected people are at high risk, we sought those that are strongly associated with specific HIV-related oral lesions and with progression of HIV disease. DESIGN: A cross-sectional study of HIV-positive outpatients referred to a university stomatology clinic for diagnosis and treatment of oral diseases. Each subject underwent both complete oral and cutaneous examinations. RESULTS: Among 55 men, with a median age of 41 years and a median CD4 cell count of 125/ju.l (range 0–950/pil), 93% had active oral diseases or conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma (KS), and xerostomia, and 95% had skin conditions, including onychomycosis, dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum were associated with oral HIV-sentinel lesions (oral candidiasis, hairy leukoplakia, and KS), with low CD4 cell counts, and with AIDS. CONCLUSION: Our results suggest that xerosis and seborrheic dermatitis may be early harbingers of HIV disease progression. Their roles as predictors warrant further study, based on their associations with low CD4 cell counts and AIDS and strong co-prevalence with one of the most common HIV-related oral lesions, oral candidiasis.

To describe the prevalence of oral lesions in HIV-infected women, and to determine the association of oral lesions with the level of immunosuppression and the route of transmission.In a retrospective, cross-sectional study, a cohort of 70 HIV-infected women (median age: 32.5 y; median CD4(+)-cell count 262 per microliter) comprising 18% of all HIV-infected individuals (n = 389) was selected in an outpatient clinic. Oral lesions strongly associated with HIV-infection were evaluated.The overall prevalence of oral lesions was 27/70 (39%). Among HIV-infected women with CD4(+)-cell counts200 per microliter, the prevalence was 65% (19/29); and with counts200 per microliter, the prevalence was 27% (11/41). The prevalence of candidiasis and hairy leukoplakia was similar among those infected heterosexually or by intravenous drug use.As reported in men, these findings demonstrate that oral lesions are common in HIV-infected women. Candidiasis is more likely to occur at low CD4(+)-cell counts, whereas no difference was seen regarding the level of immunosuppression and hairy leukoplakia. Interestingly, the route of transmission does not play a role regarding the presence of oral lesions among HIV-infected women.

OBJECTIVES: To determine whether there are any differences in the oral manifestations of sub-groups of persons with HIV. These data could provide information for planning of oral health promotion and prevention programmes. DESIGN: A comparative inter-group cross-sectional investigation of the oral manifestations of HIV. Ethnic, gender and sexual orientation differences were taken into consideration. SETTING: Three large general hospitals that offer comprehensive medical investigations and care to persons with HIV. SUBJECTS AND METHODS: A total of 485 HIV-positive adults participated. Clinical examination and, where necessary, swabs or smears of lesions for microbiology, biopsies for histology. MAIN OUTCOME MEASURES: Presence of lesions, associated signs, incidence and type of micro-organisms. RESULTS: A total of 485 HIV-positive persons were examined over a period of 3 years consisting of 225 Blacks, 191 Coloureds (persons of ‘mixed’ descent) and 69 Whites. Data were analysed using, where relevant, the X2 test or Fisher's exact test. Heterosexual males revealed a higher prevalence of all oral lesions combined when compared with heterosexual females. A similar finding was evident when HIV-associated periodontal diseases was compared in these two groups. Homosexual males had a higher prevalence of candidal infections than heterosexual males. Coloured heterosexuals had a higher prevalence of oral lesions combined than black heterosexuals. All these results showed statistical significance. CONCLUSIONS: The study tends to show that different patterns of prevalence emerge when inter-group comparisons are made of oral soft tissue diseases evident in HIV-infected South Africans.

OBJECTIVE: (1) To assess the extent of knowledge acquired since 1981 on the epidemiology of HIV-related oral manifestations in women; (2) to determine if these findings differ by gender; and (3) to assess the needs and direction for future epidemiologic research on oral disease and HIV infection in women in relation to men. DATA IDENTIFICATION: A computer-assisted search was conducted to identify epidemiologic studies reporting the frequency of various oral conditions in HIV-infected women. Studies on periodontal disease as manifestation of HIV infection were not included. DATA EXTRACTION: Methods used in the retrieved articles were reviewed with respect to target population, study design, sampling scheme, outcomes, measurements, and statistical issues. Results were summarized in relation to oral findings in HIV-infected men. RESULTS OF DATA SYNTHESIS: Most studies were prospective, and sample selection was non-random. Studies differed with respect to geographic location, risk category for HIV transmission, and stage of HIV disease. Despite these differences, oral lesions were found in at least 15% of HIV-infected women, and the most common oral lesion in all studies was candidiasis. Women differed from men with respect to the prevalence of hairy leukoplakia and Kaposi's sarcoma (KS) both of which were significantly less common in women. CONCLUSION: Future epidemiologic studies should be directed at identifying cofactors involved in addition to Epstein-Barr virus (EBV) in the development of hairy leukoplakia, and in addition to KS herpes virus (KSHV) in the occurrence of KS.