The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

Oral health-related quality of life among HIV-infected and at-risk women.

OBJECTIVES: Objective measures of dental diseases reflect only their clinical end-point. There is a need to use multidimensional measures of diseases that consider their psychosocial aspects and functional impact. The aim of this study is to compare the oral health-related quality of life (OHRQOL) between a group of HIV-infected women and a similar group of at-risk HIV-uninfected women, and to investigate the role of potential confounding clinical oral health and behavioral factors. METHODS: Our sample included HIV-infected women (87%) and women at risk for HIV infection (13%) followed up for 5.5 years. OHRQOL was measured using the short version of the Oral Health Impact Profile (OHIP-14), which is a validated and reliable instrument. RESULTS: HIV-infected women averaged 10% poorer OHRQOL than HIV-uninfected women; this difference was not apparent after adjusting for the number of study visits attended and significant behavioral and clinical oral health factors. The OHRQOL was inversely related to dental and periodontal diseases and to smoking and freebase cocaine use; these relationships were not confounded by HIV status. CONCLUSIONS: The study identified specific clinical and behavioral factors where dental professionals can intervene to possibly improve the OHRQOL of HIV-infected or at-risk HIV-uninfected women.

Dental caries in HIV-seropositive women.

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.

Incidence of oral lesions in HIV-1-infected women: reduction with HAART.

Few studies assess the effectiveness of HAART on reducing the incidence and recurrence of oral lesions. We investigated such changes among 503 HIV+ women over six years in the Women's Interagency HIV Study. The incidence of erythematous candidiasis (EC), pseudomembranous candidiasis (PC), hairy leukoplakia (HL), and warts was computed over follow-up visits after HAART initiation compared with before HAART initiation. Analysis of our data demonstrates a strong decrease in candidiasis after HAART initiation. The incidence of EC fell to 2.99% from 5.48% (RR 0.545); PC fell to 2.85% from 6.70% (RR 0.425); and EC or PC fell to 3.43% from 7.35% (RR 0.466). No changes were seen in HL or warts. Higher HIV-RNA was associated with greater incidence of candidiasis and HL, but not warts. Analysis of these data indicates that recurrence and incidence of candidiasis are reduced by HAART, and that recurrence is reduced independently of CD4 and HIV-RNA.

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 mucosal lesions and HIV viral load in the Women's Interagency HIV Study (WIHS).

The prevalence of oral lesions was assessed in a five-center subset of the Women's Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposi's sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/microl, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.

Oral mucositis with features of psoriasis: report of a case and review of the literature.

An unusual case of oral mucositis with features of psoriasis is reported along with a review of the cases of oral psoriasis in the literature. The case reported involved a crusted lesion on the upper lip and erythematous lesions on the labial mucosa, buccal mucosa, and denture-bearing palatal mucosa. In addition, lesions resembling geographic tongue and ectopic geographic tongue were present. All lesions exhibited multiple small pustules. The review of the literature compares the distribution and clinical appearance of previously reported cases of oral psoriasis.

Oral candidiasis in HIV infection: predictive value and comparison of findings in injecting drug users and homosexual men.

The objectives of this study were to compare the relationship of oral candidiasis to HIV status, cohort and CD4+ lymphocyte values in injecting drug users and homosexual men and to examine its impact on prognosis. An oral examination was added to an ongoing longitudinal study of HIV infection. Data obtained at 6-month intervals included smoking, illicit drug use, medication use, symptoms and medical diagnoses, physical examination findings and laboratory data. In this study HIV+ subjects were much more likely to present with oral candidiasis than were HIV- subjects (OR = 6.3, P < 0.01). Injecting drug users, regardless of serostatus, were more likely than homosexual men to present with oral candidiasis (OR = 3.0, P = 0.001). In both cohorts oral candidiasis was associated with low CD4+ lymphocyte counts and percent ages, and Kaplan-Meier survival estimates showed that subjects with oral candidiasis had a poorer prognosis than those without candidiasis, even after controlling for CD4+ lymphocyte count.

Oral manifestations of human immunodeficiency virus infection.

This article includes the oral manifestations which have been reported to be associated with human immunodeficiency virus (HIV) infection. The clinical appearance, diagnostic criteria and treatment of fungal, viral and bacterial infections, neoplasms and lesions of uncertain etiology are described. Accurate diagnosis of the oral lesions is important in the management of patients infected with HIV. Identification of oral lesions may suggest the need for HIV testing or may be an indicator for preventive intervention. Early identification, diagnosis and treatment may prevent extensive tissue destruction and may improve the quality of life for HIV-infected patients.

A prospective study of oral lesions and their predictive value for progression of HIV disease.

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.

Oral lesions as markers of severe immunosuppression in HIV-infected homosexual men and injection drug users.

OBJECTIVES: We examined the diagnostic utility of the presence of oral lesions, individually and in combination, in identifying severe immunosuppression, defined as CD4 cell count under 200. STUDY DESIGN: Data were collected on 82 HIV-seropositive homosexual men and 82 HIV-seropositive injection drug users who volunteered to participate in a longitudinal study of HIV infection. CD4 cell counts were measured within 24 hours of oral examination. METHODS: Sensitivity, specificity, positive predictive value, negative predictive value, and the odds ratio were computed to assess the association between oral lesions and CD4 less than 200. In addition to the individual lesions, we studied the diagnostic properties of sets of three to six lesions. For each set of lesions, a patient was classified as positive for the set if he or she had one or more lesions in that set. RESULTS: In homosexual men and injection drug users, individual lesions had low sensitivity, high specificity, and moderate positive and negative predictive values. Odds ratios reflected weak correlation to immunosuppression. When lesion sets were considered in homosexual men, sensitivity rose dramatically with only modest decreases in specificity. The positive and negative predictive values remained almost the same. Similar results for lesion sets were obtained in injection drug users, with greater reduction in specificity but stable positive and negative predictive values. Odds ratios indicated that for homosexual men, the more lesions included in the set, the stronger the correlation with immunosuppression. For injection drug users, strong correlations were observed for all lesion sets. CONCLUSIONS: Analysis of sensitivities and odds ratios in homosexual men suggest that it may be valid to note the occurrence of a greater number of oral lesions than is currently done in staging patients with HIV infection. Among injection drug users, monitoring a larger number of lesions neither improves nor reduces the correlation to severe immunosuppression.

The accurate diagnosis of oral lesions in human immunodeficiency virus infection. Impact on medical staging.

OBJECTIVE: To compare identification of oral candidiasis (OC) and oral hairy leukoplakia (OHL) by medical examiners and oral/dental examiners and to assess the impact of these diagnoses on the medical staging of the human immunodeficiency virus (HIV). DESIGN: Retrospective analysis of data collected by medical and oral/dental examiners at the baseline examination of a prospective study. SETTING: Homosexual men and men and women who were parenteral drug users residing in New York City, enrolled in a longitudinal cohort study. SUBJECTS: A total of 245 individuals participated in this study. MAIN OUTCOME MEASURES: The diagnoses of OC and OHL as recorded in the medical and oral/dental charts were analyzed retrospectively for the same medical and oral/dental evaluation visits. The medical staging of HIV infection based on that evaluation was analyzed concomitantly. RESULTS: Among homosexual men, the oral/dental examiners diagnosed OC in 11% of the individuals and the medical examiners in 4%. In the same cohort, OHL was diagnosed by the oral/dental examiners in 14% of the individuals and by the medical examiners in 8%. Among the parenteral drug users the oral/dental examiners diagnosed OC in 29% of the individuals while the medical examiners made this diagnosis in 11%. In the same cohort, OHL was diagnosed by the oral/dental examiners in 9% of the individuals and by the medical examiners in 2%. The OC and OHL diagnoses affected the medical staging of 12% of the HIV-positive homosexual men and of 22% of the HIV-positive parenteral drug users. Forty percent of the HIV-positive homosexual men and 79% of the HIV-positive parenteral drug users with stage-defining oral lesions were not properly identified by the medical examiners. CONCLUSIONS: Specific training and a comprehensive oral examination have a significant impact on the diagnoses of OC and OHL, and on the medical staging of individuals with HIV infection.

Oral manifestations of HIV infection in homosexual men and intravenous drug users. Study design and relationship of epidemiologic, clinical, and immunologic parameters to oral lesions.

This article describes the baseline findings from a study designed to compare the oral manifestations of HIV infection in homosexual men and intravenous drug users. Both seropositive and seronegative persons were studied. A standard examination instrument was developed to record indexes of oral disease as well as to record the presence of oral lesions. The two groups differed in terms of education, race, socioeconomic status, employment status, housing, and smoking experience. The prevalence and type of oral lesions differed in the two seropositive groups. In seropositive homosexual men, white lesions on the tongue (28.4%) predominated; whereas for the seropositive intravenous drug users, oral candidiasis (43.0%) and gingival marginal erythema (33.3%) were most often detected. We also observed that seronegative intravenous drug users displayed a greater number of oral lesions than seronegative homosexual men. For seropositive homosexual men, lesion presence was significantly associated with decreased levels of CD4; positive associations were seen with current smoking, antiviral drug use, and antibiotic use, and a negative association was observed with current employment. In contrast, only exposure to antiviral drugs was significantly correlated with lesion presence for seropositive intravenous drug users. This baseline analysis from our longitudinal study suggests clear differences in oral manifestations of HIV infection between seropositive homosexual men and intravenous drug users and between seronegative homosexual men and intravenous drug users. Among other parameters, it is apparent that lifestyle, access to health care, and the condition of the oral cavity before infection influence the development of oral lesions in persons with HIV infection.

In situ detection of lytic Epstein-Barr virus infection: expression of the NotI early gene and viral interleukin-10 late gene in clinical specimens.

Riboprobes that detect two genes expressed only during productive infection were developed to characterize the clinical spectrum of Epstein-Barr virus (EBV) lytic infection and identify diseases that may be responsive to antiviral drug therapy. The NotI antisense probe hybridizes to tandem repeats in the abundant early lytic cycle BHLF1 mRNA. Transcripts were detected in lytically infected cell lines, AIDS-associated oral hairy leukoplakia, bone marrow of a patient with virus-associated hemophagocytic syndrome, and spleen of an AIDS patient but not in EBV-positive primary central nervous system lymphomas or in circulating EBV-infected B cells from a patient with acute infectious mononucleosis. The viral (v) interleukin-10 (IL-10) probe hybridizes to the unique 5' end of the late lytic cycle BCRF1 mRNA, which encodes a protein homologous to the human cytokine IL-10. The vIL-10 probe detected transcripts in lytically infected cell lines and within the differentiated layers of oral hairy leukoplakia.

Cytomegalovirus infections of the oral cavity. A report of six cases and review of the literature.

Cytomegalovirus is responsible for a significant percentage of asymptomatic viral infections worldwide. Although virtually any cell or organ may be infected, involvement of the oral cavity is uncommon. Only nine well-documented examples of intraoral cytomegalovirus infections were found in a review of the English-language literature. We report six additional examples, five of which possessed unique clinical and histopathologic characteristics. The light and electron-microscopic features of cytomegalovirus are discussed, as well as diagnostic adjuncts such as immunohistochemistry and deoxyribonucleic acid in situ hybridization.

Major aphthous-like ulcers in patients with AIDS.

This report describes persistent, painful oral ulcers that occurred in nine patients with the acquired immunodeficiency syndrome (AIDS). These ulcers resembled major aphthous ulcers in clinical appearance and response to therapy. They occurred less frequently in patients with AIDS than those caused by herpes simplex and were found in 4 of 346 (1.1%) patients with AIDS at one medical center. Lesions were typically painful. Identification and treatment with topical tetracycline and steroids led to resolution with relief of symptoms. Further study is necessary to understand the etiology and pathogenesis of these ulcers.

Recurrent botryoid odontogenic cyst (lateral periodontal cyst).

The terms botryoid odontogenic cyst and lateral periodontal cyst have both been used to describe a histologically distinct type of cyst characterized by a thin epithelial lining exhibiting focal thickenings or plaques. The cyst reported herein is a well-documented example of this type of cyst, which exhibited persistent and recurrent behavior.

Oral Kaposi's sarcoma: a clinicopathologic study of 23 homosexual and bisexual men from the New York metropolitan area.

A total of 3970 cases of Kaposi's sarcoma (KS) associated with the acquired immunodeficiency syndrome had been reported to the Centers for Disease Control by the end of 1986. The prevalence of oral KS in patients with KS of the skin varies, reaching a maximum of 44% in one published study. We present a retrospective clinicopathologic analysis of 23 previously unreported cases of oral KS in male homosexual and bisexual patients from the New York metropolitan area. Our data reveal that 21 of the patients had KS confined to the oral cavity and that, in 16 cases, the oral KS was the first presenting sign of the acquired immunodeficiency syndrome. Sixteen of the 23 patients had solitary oral lesions. Nineteen of the tumors showed prominent endothelium-lined capillaries resembling lymphatics, 16 exhibited a prominent spindle cell component, and 17 demonstrated areas of fibrosis. Of the 13 patients for whom there was adequate follow-up information, five were dead within 6 to 15 months. All five deaths were due to Pneumocystis pneumonia.

Resolution of oral hairy leukoplakia during treatment with azidothymidine.

This report presents a case of oral hairy leukoplakia that has completely disappeared during treatment with azidothymidine. The reason for the resolution of the lesions in this case is not certain, but the outcome may be due to the action of the drug on the agent or agents causing the lesion.

Oral findings in patients with acquired immunodeficiency syndrome.

Oral examinations of 103 consecutive patients with acquired immunodeficiency syndrome (AIDS) were performed. Of these patients, 74 (72%) were heterosexuals and 29 (28%) were homosexual or bisexual men. Lesions that were identified on subsequent examination were recorded separately. Oral candidiasis was the most common finding, occurring in 94 patients. Other findings were herpes simplex ulceration (ten patients), exfoliative cheilitis (nine patients), xerostomia (ten patients), "hairy" leukoplakia (seven patients), and Kaposi's sarcoma (four patients). A patchy, depapillated tongue was seen in six patients, and ulcers with uncertain cause were seen in three patients. Gingival bleeding, perioral molluscum contagiosum, and brown hairy tongue each occurred in one patient. In this study, "hairy" leukoplakia and Kaposi's sarcoma occurred exclusively in homosexual and bisexual men with AIDS, and occurred significantly more frequently in this group than in heterosexual patients with AIDS. There was no significant difference between these groups in the frequency of occurrence of other findings.