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HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

Primary burning mouth syndrome (BMS) is a chronic, idiopathic intraoral mucosal pain condition that is not accompanied by clinical lesions or systemic disease. There is some uncertainty whether this condition should be referred to as a disease, a disorder, or a syndrome but there are insufficient data to justify any change in taxonomy at present. BMS occurs most often among women and is often accompanied by xerostomia and taste disturbances. More recently a neuropathological basis has been proposed so that BMS may be regarded as an oral dysesthesia or painful neuropathy. However, our incomplete understanding of the epidemiology, etiology, pathophysiology, and lack of diagnostic criteria are barriers to critical investigation and selection of effective treatments. There is only limited evidence to guide clinicians in the management of patients with BMS. Treatable secondary causes should be investigated before diagnosing primary BMS. Topical clonazepam and cognitive therapy have been proven efficacious in some patients. Emerging evidence supports the effectiveness of the antioxidant, alpha lipoic acid, with further studies of this agent being warranted. Additional research into mechanisms, diagnostic criteria, and randomized controlled interventional studies are needed.

Objective: To assess the educational preparedness of medical and dental professionals to reduce the burden of OPC through planning effective cancer control strategies such as reducing tobacco consumption, suggesting healthy lifestyle and diet, and performing early detection through screening examinations and appropriate follow-up., Methods: Self-reported adequacy of training in oral and pharyngeal cancer (OPC) early intervention activities was compared among 4 health care provider groups in North Carolina. Pretested surveys were mailed to random samples of licensed professionals., Results: Nearly all providers agreed that early detection improves 5-year survival rates from OPC. Compared with 567 medical providers (273 family physicians and 294 nurse practitioners), 1235 dental providers (584 dentists and 651 hygienists) were significantly less likely to feel adequately trained in tobacco and alcohol cessation and to palpate neck nodes, but were significantly more likely to feel adequately trained to perform oral cancer examinations. Among dental providers, those who felt they had adequate training in tobacco and alcohol cessation were significantly more likely to assess these risk factors on patient medical histories., Conclusions: Education is needed to prepare dental providers to undertake OPC prevention activities, whereas medical providers would benefit from enhanced oral examination skills to improve their performance in early detection.

Objectives: To assess knowledge of oral and pharyngeal cancer (OPC) clinical signs and risk factors, the association between the risk factors and OPC, and the experience with OPC screening between newly diagnosed OPC patients and controls among a population of veterans in North Carolina., Study Design: A case-control study with 31 OPC cases and 30 frequency-matched controls recruited from 2003 to 2004. Bivariate analysis using chi-square statistics and multivariate logistic regression was implemented to estimate the association with OPC., Results: Only 34% of respondents knew 1 clinical sign and 4 or 5 risk factors for OPC. The lifetime accumulation of tobacco had a significant relationship with OPC (>20 pack-years; OR, 3.2; 95% CI, 1.01-10.3). Many respondents had not had an oral cancer examination within 3 years, mostly through ignorance. Most VA OPC patients were diagnosed by physicians, rather than by dentists., Conclusions: A considerable knowledge deficit on OPC was found among North Carolina veterans. Use of tobacco was a risk factor for OPC in this population.

Objectives: To establish incidence rates and risk factors for HIV-associated oral candidiasis (OC), oral hairy leukoplakia (OHL), and any HIV-associated oral diseases (HIV-OD)., Design: This prospective, cumulative case-control study followed 283 initially oral disease-free HIV-1-infected men and women for 2 years. Incidence rate ratios (IRR) and incidence proportions for OC, OHL, and HIV-OD were estimated. Multivariable analyses using Poisson regression determined the most parsimonious best-fitting model explaining the outcomes., Results: Incidence rate (per 1000 person-months) was 9.3 for OC, 6.8 for OHL, and 13.5 for HIV-OD. Incidence of OC was associated with low CD4 count (adjusted IRR = 3.0 (95% CI = 1.7, 5.1)), smoking (IRR = 1.9 (1.0, 3.8)) and combination antiretroviral therapy (IRR = 0.3 (0.1, 0.8)). Incidence of OHL was associated with low CD4 count, conditional upon smoking status. Conclusions Low CD4 count and smoking are important risk factors for HIV-associated OC and OHL. Antiretroviral medications are protective for OC but not for OHL.

Objective: The purpose of this article was to highlight the recent call for an evidence-based approach to public policy decision making with respect to funding dental services and the need this creates for enhanced clinical research activities., Study Design: Systematic reviews on topics of importance to oral health care practitioners are being conducted and published by various national and international groups. Recent activities to assess evidence to support medically necessary dental services were reviewed., Results: An Institute of Medicine Committee on Medicare Coverage Extensions found little published scientific evidence that directly assessed the effectiveness of dental services in preventing or managing systemic health outcomes for patients with head and neck cancer, lymphoma, leukemia, organ transplantation, and heart valve repair or replacement., Conclusions: The scientific community must strive to meet the challenge of conducting well-designed randomized, controlled trials that test the impact of dental treatment interventions on systemic health to meet the growing need for evidence to support or refute widely accepted dental treatment protocols for medically complex patients.

Objective: A systematic review of randomized clinical trials published between 1966 and April 2000 was undertaken to determine the strength of evidence for the effectiveness of antifungal drugs (nystatin, clotrimazole, amphotericin B, fluconazole, ketoconazole, and itraconazole) to prevent and treat oral candidiasis in human immunodeficiency virus-positive patients., Study Design: An automated database search identified 366 articles. Six met inclusion and exclusion criteria with respect to prophylaxis; 12 met criteria for treatment of oral candidiasis., Results: The evidence for the prophylactic efficacy of fluconazole is good, although insufficient to draw conclusions about the other antifungals. Evidence for treatment effectiveness is insufficient for amphotericin B but good for nystatin, clotrimazole, fluconazole, ketoconazole, and itraconazole., Conclusion: Suggestions for strengthening the evidence base include the following: use of larger, more well-defined groups; control for immunologic status, viral load, history of oral candidiasis, past exposure to antifungals, baseline oral Candida carriage, drug interactions, and antiretroviral therapy; and consistent use of compliance monitors, fungal speciation, and susceptibility testing.

Objectives: The purpose of this study was to assess the use of human immunodeficiency virus (HIV)-related oral opportunistic infections as markers of immune suppression and viral burden in adults with HIV/acquired immunodeficiency syndrome (AIDS)., Methods: The population consisted of a single institution observational cohort involving 606 patients with HIV/AIDS with CD4 count data and 277 with plasma viral load measurements examined between 1995 and 1999 for the presence of oral manifestations of HIV. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value is reported for the association of specific oral lesions and lesion sets with CD4 counts <200 cells/mm(3) and with plasma HIV RNA >/=20,000 copies/mL., Results: Lesions with moderate-to-high PPVs for CD4 <200 cells/mm(3) were as follows: Kaposi's sarcoma (100%; P =.035), pseudomembranous candidiasis (82. 2%; P <.001), linear gingival erythema (70.0%; P =.015), hairy leukoplakia (66.3%; P <.001), angular cheilitis (60.0%; P =.128), and erythematous candidiasis (58.3%; P =.061). Necrotizing ulcerative periodontal diseases, HIV salivary gland disease, oral ulcers, and oral warts had PPVs below 50%. Concurrent infection with candidiasis and hairy leukoplakia had the highest PPV of 89.3%; P <. 001. PPVs for HIV RNA >/=20,000 copies/mL ranged from 27.3% to 100%, with significant association only for pseudomembranous candidiasis., Conclusions: Specific common oral lesions are strongly associated with immune suppression, as measured by CD4 cell counts, and are modestly associated with high viral burden, thus serving as potential clinical markers of HIV viremia and the consequent destruction of the immune system with progressive HIV disease.

Objective: The purpose of this investigation was to quantify human immunodeficiency virus type-1 (HIV-1) RNA in saliva and plasma and identify factors associated with increased salivary viral load., Study Design: Forty HIV-1-seropositive adults underwent oral examinations to assess mucosal and periodontal health. Whole saliva was evaluated for HIV-1 RNA titer and occult blood. Plasma viral load, CD4 cell count, HIV-1 staging, and antiretroviral therapy data were obtained from medical records. Associations between salivary titers and oral/systemic parameters were analyzed by means of t tests, Wilcoxon signed rank tests, Pearson's correlation coefficient, and analysis of covariance., Results: Forty-two percent of the subjects had detectable salivary HIV-1 RNA. Oral titers were highly correlated with plasma viral levels (r = 0.51, P <.01). HIV-associated periodontal disease (in particular, linear gingival erythema), severe gingival inflammation, and absence of antiretroviral therapy were associated with high salivary titers (P <.01)., Conclusions: Substantial quantities of HIV-1 can be shed in the oral cavity, particularly when inflammatory conditions are present. Salivary titer may be a useful indicator of systemic viral burden.

Objective: The purpose of this study was to determine temporal trends in the prevalence of oral manifestations of human immunodeficiency virus (HIV)., Study Design: Five hundred seventy HIV-infected adults recruited consecutively were examined by using established presumptive clinical criteria for HIV-associated oral lesions. Prevalence of oral lesions before the widespread use of HIV protease inhibitors (February 1995 through August 1996, 8% of the early sample, n = 271) was compared with lesion prevalence in a more recent period of greater protease inhibitor use (December 1996 through February 1999, 42% of the late sample, n = 299)., Results: Overall prevalence of oral lesions significantly decreased from early to late periods, 47.6% to 37.5%, respectively (P =.01), with some variation by lesion type. Prevalence of hairy leukoplakia (25. 8% to 11.4%; P <.01) and necrotizing periodontal diseases (4.8% to 1. 7%; P =.03) decreased, whereas HIV salivary gland disease increased (1.8% to 5.0%; P =.04). Changes in prevalence of oral candidiasis (20.3% to 16.7%), aphthous ulcers (3.7% to 3.0%), oral warts (2.2% to 4.0%), herpes simplex virus lesions (1.8% to 2.0%), and Kaposi's sarcoma (1.1% to 0.3%) were not statistically significant (P >.20 for all comparisons)., Conclusion: The pattern of oral opportunistic infections is changing in the era of protease inhibitor use.

Objective: The purpose of this study was to determine the prevalence and severity of and the factors associated with peripheral blood cytopenias among HIV-infected patients., Study Design: The investigation involved 516 HIV-infected adults in a longitudinal study of oral disease. Prevalence of hemoglobin, hematocrit, white blood cell, neutrophil, lymphocyte, and platelet values below the lower limit of normal and certain hematologic "critical values" were determined. Demographic, clinical/immunologic/viral stage, medications, and oral lesions were assessed for association with cytopenias by chi(2) and bivariate analyses., Results: Findings with respect to prevalence were as follows: anemia, 51%; leukopenia, 43. 4%; neutropenia, 27.5%; lymphopenia, 20.7%; thrombocytopenia, 15.5%. Severe cytopenias were detected in fewer than 1% of the patients. Severity of HIV clinical disease and CD4 cell count depletion were significantly associated with all cytopenias. High viral load was associated only with the leukopenias. Black race, antiparasitic therapy, and some oral lesions were associated with certain cytopenias., Conclusions: In HIV-infected patients, mild cytopenias are common; however, severe anemia, neutropenia, and thrombocytopenia that may predispose to certain oral manifestations and dental surgical complications are rare.