[show abstract][hide abstract] ABSTRACT: Oropharyngeal candidiasis (OPC) is the most common oral infection in HIV(+) persons. Previous studies suggest a role for CD8(+) T cells against OPC when CD4(+) T cells are lost, but enhanced susceptibility to infection occurs when CD8(+) T-cell migration is inhibited by reduced tissue E-cadherin. Objective: To conduct a longitudinal study of tissue CD8(+) T-cells and E-cadherin expression before, during, and after the episodes of OPC.
Oral fungal burden was monitored and tissue was evaluated for CD8(+) T cells and E-cadherin over a 1-year period in HIV(+) persons with a history of, or an acute episode of, OPC.
While longitudinal analyses precluded formal interpretations, point prevalence analyses of the data set revealed that when patients experiencing OPC were successfully treated, tissue E-cadherin expression was similar to that in patients who had not experienced OPC, and higher numbers of CD8(+) T cells were distributed throughout OPC(-) tissue under normal expression of E-cadherin.
These results suggest that (1) reduction in tissue E-cadherin expression in patients with OPC(+) is not permanent, and (2) high numbers of CD8(+) T cells can be distributed throughout OPC(-) tissue under normal E-cadherin expression. Together, these results extend our previous studies and continue to support a role for CD8(+) T cells in host defense against OPC.
[show abstract][hide abstract] ABSTRACT: This workshop reviewed aspects of the following: oral fungal disease in HIV-infected patients and the predictive value of oral mucosal disease in HIV progression; the role of the oral biofilms in mucosal disease; microbial virulence factors and the pseudomembranous oral mucosal disease process; the role that oral mucosal disease may have in HIV transmission; and the available topical antifungal treatment. This article summarizes the ensuing discussions and raises pertinent problems and potential research directions associated with oral fungal disease in HIV-infected patients, including the frequency of oral candidosis, the role of the intraoral biofilm in the development of oral mucosal disease, and host-pathogen interactions, as well as the development of the fetal oral mucosa, neonatal nutrition, and the role of oral candidosis in this setting. Finally, discussions are summarized on the use of inexpensive effective antifungal mouthwashes in resource-poor countries, the potential stigmata that may be associated with their use, as well as novel topical medications that may have clinical applicability in managing oral candidal infections in HIV-infected patients.
[show abstract][hide abstract] ABSTRACT: Human Papillomavirus-32 (HPV-32) has traditionally been associated with focal-epithelial-hyperplasia (FEH). It is also present in 58% of oral warts of HIV-positive individuals whose prevalence is increasing. Current methods for the detection of HPV-32 are labor-intensive and insensitive so the goal of this work was to develop a highly sensitive and easy to use specific polymerase chain reaction (PCR) assay.
An HPV-32 L1 specific PCR assay was developed and optimized. The sensitivity and specificity was compared to previous assays utilized for detection (PGMY and MY09/11 PCR with dot blot hybridization) using cloned HPV-32 L1, the closely related HPV-42 L1 as well as clinical samples (oral swabs and fluids from 89 HIV-positive subjects).
The HPV-32 specific PCR assay showed improved sensitivity to 5 copies of HPV-32 as compared to the PGMY PCR, MY09/11 PCR and dot blot which had a limit of detection of approximately 3,000 copies. Using the HPV-32 dot blot hybridization assay as the gold standard, the HPV-32 specific PCR assay has a sensitivity of 95.8% and 88.9% by sample and subject, respectively, and specificity was 87.8% and 58.8% by sample and subject, respectively. The low sensitivity is due to the HPV-32 specific PCR assays ability to detect more HPV-32 positive samples and may be the new gold standard.
Due to the ease, sensitivity, and specificity the HPV-32 specific PCR assay is superior to previous assays and is ideal for detection of HPV-32 in large cohorts. This assay provides an excellent tool to study the natural history of HPV-32 infection and the development of oral warts.
[show abstract][hide abstract] ABSTRACT: In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis (OPC) is often associated with the accumulation of CD8+ T cells at the epithelial/lamina propria interface within the lesion together with increased tissue-associated cytokines and chemokines. Despite this reactivity, a dysfunction in the ability of the CD8+ cells to reach the organism at the outer epithelium is postulated. The purpose of this study was to examine chemokine receptors present in the OPC lesions for a potential role in susceptibility to infection.
Biopsies taken from buccal mucosa of HIV- persons, healthy mucosa of HIV+ OPC- persons, and OPC lesions were processed for protein immunohistochemical staining or RNA analysis by real-time PCR and Superarray.
There was little change in expression of chemokine receptors at the protein or RNA level between OPC+ and OPC- tissue. At the protein level, increases occurred in OPC+ persons only if associated with CD8 cells. In the Superarray, of the 22 chemokine receptor mRNAs expressed, c. 90% remained unchanged (< 1.0-fold change) between HIV- and HIV+ tissue and between HIV+ OPC- and HIV+ OPC+ tissue.
Tissue-associated chemokine receptor expression does not appear to contribute to the dysfunction in cellular migration associated with susceptibility to OPC.
[show abstract][hide abstract] ABSTRACT: Oropharyngeal candidiasis (OPC) is the most frequently observed oral infection in HIV-infected individuals. Historically, lower CD4 counts have been associated with an increased prevalence of OPC in HIV-infected patients, but HIV viral load has also recently been recognized as a possible predictive factor.
We examined the impact of viral load and blood CD4 cell count on the occurrence of OPC using modern exploratory statistical analyses.
The exploratory and inferential methods of classification and regression trees (CARTs) and logistic regression were used to compare the impact of viral load and CD4 cell counts on OPC status in 161 HIV-infected individuals from an outpatient clinic population in New Orleans.
The use of stepwise logistic regression and CART to classify individual OPC status both identified viral load as the most important covariate, followed by CD4 cells counts. Age, sex, and highly active antiretroviral therapy use were also found to be associated with OPC status.
These data strongly suggest that low viral load distinguishes those not at risk for OPC with high viral load, which also includes a heterogeneous set of predictors for OPC status, has the highest impact on OPC classification.
[show abstract][hide abstract] ABSTRACT: Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common oral infection in HIV(+) persons. Oral epithelial cells are considered important for innate host defense against OPC with production of cytokines in response to C. albicans and the ability to inhibit Candida growth in vitro. The purpose of this study was to determine if Candida similarly induces cytokines by oral epithelial cells from HIV(+) persons, including those with OPC, as well as to determine if cytokines can influence the oral epithelial cell anti-Candida activity.
Supernatants from oral epithelial cells from HIV(+) persons with and without OPC cultured with Candida were evaluated for cytokines by ELISA, or cytokines were added to the standard growth inhibition assay using epithelial cells from HIV(-) persons.
Results showed low Candida-induced epithelial cell cytokine production from HIV(+) persons, but with some elevated proinflammatory cytokines (TNF-alpha, IL-6) in those with OPC compared to those without OPC. The addition of specific proinflammatory or Th cytokines had no effect on oral epithelial cell anti-Candida activity in healthy HIV(-) persons.
These results suggest that oral epithelial cells from HIV(+) persons can contribute at some level to the oral cytokine milieu in response to Candida during OPC, but that cytokines do not appear to influence oral epithelial cell anti-Candida activity.
[show abstract][hide abstract] ABSTRACT: Oropharyngeal candidiasis (OPC) remains the most common oral infection in human immunodeficiency virus (HIV) disease. In a high percentage of HIV(+) persons with reduced CD4(+) T cells, oral lesions with Candida present at the outer epithelium have an accumulation of CD8(+) T cells at the epithelium-lamina propria interface associated with reduced expression of the mucosal cell-trafficking adhesion molecule E-cadherin. The purpose of the present study was to characterize the immune status of these CD8(+) T cells. Immunohistochemical staining for phenotypic and activation and costimulation markers was performed on frozen biopsy tissue sections from HIV(+) OPC(+) persons with accumulated CD8(+) T cells. CD8(+) T cells consisted primarily of central memory cells by virtue of positive CD45RO (memory) and CD27 (central memory) expression. However, concomitant negative expression of CD62L and CCR7 (effector memory) was suggestive of a transitioning memory phenotype within the tissue. Despite this, the cells are considered to be activated on the basis of positive expression of CD69. The CD8(+) T cells are not considered to be NK T cells or anti-HIV CD8(+) T cells because of negative or low expression of CD161 and vascular cell adhesion molecule, respectively. These results suggest that the accumulated mucosal migratory-challenged CD8(+) T cells are otherwise normal memory T cells in an activated state.
Clinical and Vaccine Immunology 07/2006; 13(6):678-83. · 2.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: The increases incidence of oral human papillomavirus (HPV) in patients infected with the human immunodeficiency virus (HIV) is of concern and is the focus of numerous current research studies. Recent studies have shown an increased risk of oral warts in HIV-infected individuals despite treatment with highly active antiretroviral therapy (HAART). There seems to be a predilection for the labial mucosa as a site specific for occurrence for oral warts. This reports presents a series of case reports documenting the same observation.
[show abstract][hide abstract] ABSTRACT: This retrospective study evaluated the success rate of root canal therapy in 157 HIV-positive patients who had undergone nonsurgical endodontic treatment in a dedicated clinic between 1998 and 2004. Dental records and radiographs were reviewed and information concerning age, gender, medical history, anti-retroviral medication, treatment dates, and follow-up evaluation was compiled. All root canal treatment was performed following the clinical guidelines of the American Association of Endodontists. A single practitioner who was responsible for seeing all of the patients at the six-month recall examination reviewed radiographs. Success was defined as the absence of pain and swelling as well as the absence of the periapical lesion (or a reduction in size compared to its preoperative radiographic size). At the six-month postoperative evaluation, a success rate of 90% was observed in the study group. No statistically significant differences were noted when the success of the root canal therapy was related to the symptomatic clinical presentation, the antiretroviral therapy, or the viral load.
[show abstract][hide abstract] ABSTRACT: Prevalence of human papillomavirus (HPV)-associated oral condylomas has reportedly increased in HIV-infected individuals since the introduction of highly active antiretroviral therapy (HAART). The relationships between HIV therapy regimen, overall health, and subclinical oral HPV have not been examined.
To determine oral HPV genotype prevalence and the impact of HAART and health in the HIV+ population.
An L1 consensus-primer polymerase chain reaction and linear array assay were used to examine the prevalence of 27 HPV genotypes in saliva of 98 HIV+ individuals. Risk assessment variables were compared to oral HPV status.
Oral HPV was detected in 37% of HIV+ African American individuals. Caucasians were at greater risk of oral HPV infection than African Americans. Markers of advanced HIV disease did not predict HPV status. Therapy status was associated with HPV detection.
Treatment of HIV, rather than HIV immunosuppression, appears to play a role in oral HPV infections in HIV+ individuals.
Sex Transm Dis 12/2005; 32(11):703-9. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent studies have shown an increased risk of oral warts in HIV+ individuals despite treatment with highly active antiretroviral therapy (HAART). Human papilloma virus (HPV) infection has attracted a great deal of attention, not just because of the difficulty of managing oral warts but also because of the oncogenic potential of certain strains, in particular HPV-16 and -18, which have been detected in 20–30% of oral squamous cell carcinomas. Between 1999 and 2004, DNA extraction was performed using a multiplex PCR reaction to detect and type HPV in 12 HIV-positive adult with a clinicopathologic diagnosis of Oral Warts. HPV was detected in 11 of the 12 orals warts. HPV-32 was present in all subjects, whereas only one subject had a co-infection of HPV-32 and -7. Future studies should examine the specific roles of these specific HPV types and whether a potential link exists for oral premalignant lesions.
[show abstract][hide abstract] ABSTRACT: Anti-Candida activity by oral epithelial cells is considered one of several innate mucosal defense mechanisms against oropharyngeal candidiasis (OPC). OPC is the most common fungal infection in HIV disease. Previously we reported that oral epithelial cell anti-Candida activity is reduced in those with OPC, potentially representing a contributing factor to OPC. However, testing clinical epithelial cells possessing high levels of Candida has been limiting due to high background in the assay controls. HIV+ smokers often develop OPC sooner than non-smokers during progression to AIDS, suggesting additional immune aberrations. The purpose of this study was to design a means to reduce Candida associated with epithelial cells collected from saliva without affecting their in vitro growth inhibitory activity, and to employ that approach to evaluate antifungal activity in HIV+ smokers. To do so, oral epithelial cells with and without known levels of Candida were subjected to various treatments including azole, polyene, or echinocandin antifungal drugs or fixation followed by the standard growth inhibition (GI) assay. The results indicated that antifungal drugs, while effectively reducing cell-associated Candida, also affected epithelial cell function. In contrast, fixation with paraformaldehyde eliminated cell-associated Candida and had minimal effects on epithelial cell anti-Candida activity. Employing the fixation design that allowed a broad range of patients to be evaluated showed no difference in oral epithelial anti-Candida activity between HIV+ smokers and non-smokers. Therefore, oral epithelial cell antifungal activity does not appear compromised in those who smoke, reducing it as a contributing factor in susceptibility to premature OPC.
Medical Mycology 10/2005; 43(6):517-23. · 1.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Oropharyngeal candidiasis (OPC), the most common oral infection in human immunodeficiency virus-positive persons, correlates with reduced blood CD4+ T cells. In those with OPC, CD8+ T cells accumulate at the lamina propria-epithelium interface at a distance from the organism at the outer epithelium. The present study aimed to characterize the tissue-associated CD8+ T cells and tissue microenvironment in both OPC+ and OPC- persons. The results show that the majority of CD8+ T cells possess the alphabeta T-cell receptor, the thymus-derived alphabeta CD8 antigen heterodimer, and similar levels of the alpha(4)beta(7), alpha(4)beta(1), and alpha(e)beta(7) homing receptors. Studies to evaluate the tissue microenvironment showed that in OPC+ persons, the adhesion molecule for T cells to enter mucosa, mucosal addressin cell adhesion molecule, is significantly increased, whereas E-cadherin, which allows T cells to migrate through mucosa, is significantly decreased compared to OPC- persons. These results continue to support a role for CD8+ T cells against OPC under conditions of reduced numbers of CD4+T cells, with susceptibility to infection potentially associated with a dysfunction in mucosal CD8+ T-cell migration by reduced tissue-associated E-cadherin.
Infection and Immunity 07/2005; 73(6):3659-67. · 4.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Oral warts, caused by human papillomavirus (HPV), and oral hairy leukoplakia (OHL) caused by Epstein-Barr virus (EBV), are common oral manifestations in HIV-infected persons. Although both conditions occur most often with reduced blood CD4+ T-cell numbers, oral warts and OHL rarely occur simultaneously, suggesting that dysfunctions in other secondary local immune parameters are also involved. The present study evaluated tissue-associated proinflammatory and T-helper cytokine and chemokine mRNA expression and the presence of T cells in each lesion.
Biopsies were taken from lesion-positive and adjacent lesion-negative sites of HIV+ persons with oral warts or OHL and lesion-negative sites from HIV+ persons who were oral HPV or EBV DNA-positive (matched controls). Cytokine/chemokine mRNA expression was quantified by real-time polymerase chain reaction. CD3, CD4, and CD8 cells were identified by immunohistochemistry.
No differences were detected in tissue-associated cytokine/chemokine mRNA expression in warts or OHL when compared to lesion-negative sites. Immunohistochemical analysis of T cells showed CD8+ cells exclusively, but few cells were present in either lesion. No differences were detected between lesion-positive and -negative control sites of each pathologic condition.
Little evidence was found for local immune reactivity to either oral warts and OHL, suggesting that CD4+ T cells are a primary host defense against both oral warts and OHL, but with nonimmune factors potentially responsible for the divergent prevalence of each.
Oral Microbiology and Immunology 07/2005; 20(3):154-62. · 2.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: Human papilloma virus (HPV) is the most common sexually transmitted viral disease responsible for mucosal warts and anogenital malignancies. HPV-associated oral lesions include condyloma, focal epithelial hyperplasia and some squamous cell carcinomas. Both oral and genital lesions caused by HPV are more commonly seen in those co-infected with HIV. While there is some degree of HPV genotypespecific clinical presentation, unusual manifestations of oral HPV disease in the HIV-positive patient frequently occur. Examinations of oral-wart biopsy specimens from HIV-positive individuals reveal a range of HPV genotypes, including cutaneous type 2; genital types 6, 11, 16 and 18; and oral type 13. However, the most common HPV genotypes identified in HIV-associated oral warts are oral specific HIV type 32 and the cutaneous HPV type 7. This paper presents two cases of HPV lesions associated with these types, which progressed into oral squamous cell carcinoma.
[show abstract][hide abstract] ABSTRACT: Oral opportunistic infections in the HIV-positive individual have been documented since the first reports of the epidemic, with many lesions associated with reduced CD4(+) T lymphocyte cell count. The most common oral lesions seen in HIV disease prior to the advent of highly active antiretroviral therapy (HAART) were oropharyngeal candidiasis and oral hairy leukoplakia. However, since the advent of HAART while many oral lesions have decreased significantly the incidence of oral warts has surprisingly increased. Despite the correlation of diminished CD4(+) T lymphocyte count to the occurrence of these lesions, it is rare for the lesions to occur concurrently suggesting that each pathologic lesion type is associated with distinct host immune dysfunctions. To date, the oral opportunistic infection most frequently investigated is oropharyngeal candidiasis, where data suggests that both systemic and local immunity is important for protection against infection. In contrast, recent investigations into the host responses associated with oral hairy leukoplakia and oral warts show little to no evidence of systemic or mucosal immune responsiveness despite the presumed competence of several types of leukocytes other than CD4(+) T cells. Together these data are suggesting that susceptibility to oropharyngeal candidasis in HIV-positive persons is predominantly immune-based, whereas protection or susceptibility to oral hairy leukoplakia and oral warts may be more associated with factors other than mucosal immune function.
AIDS PATIENT CARE and STDs 09/2004; 18(8):443-56. · 3.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common infection in human immunodeficiency virus (HIV)-positive persons. Although CD4(+) T cells are considered to be important for host defense against C. albicans at the oral mucosa, a recent immunohistochemical evaluation of T cells in OPC lesions of HIV-positive persons with reduced CD4(+) T cells showed high numbers of CD8(+) T cells. The present study investigated tissue-associated expression of cytokine and chemokine mRNA at the site of infection. Results showed some effects of HIV (primarily increased chemokine mRNA levels) but little effect of blood CD4(+) T cells. In contrast, mRNA for several proinflammatory, T helper, and CD8(+) T cell-associated cytokines and chemokines were increased in subjects with OPC versus those without. These results support the presence of CD8(+) T cells in OPC lesions and suggest evidence for a response against OPC, despite reduced levels of CD4(+) T cells.
The Journal of Infectious Diseases 09/2004; 190(3):605-12. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: The possibility of increases in both oral and anogenital pathologic conditions due to human papillomavirus (HPV) in patients infected with the human immunodeficiency virus (HIV) is of concern and is the focus of numerous current research studies. HIV-infected women are at higher risk for cervical HPV detection, for infection with high-oncogenic-risk types of HPV, for persistent HPV infection, for cervical cytologic abnormalities, and for cervical intraepithelial neoplasms. HIV-infected men are at increased risk for anal HPV infection, for anal infection with high oncogenic-risk types of HPV, for persistent anal HPV infection, and for anal intraepithelial defects. Recent studies have shown an increased risk of oral warts in HIV-infected individuals despite treatment with highly active antiretroviral therapy (HAART). Oral HPV infection rates have not declined since the initiation of HAART, and evidence suggests that the rates may have actually increased in white HIV-infected males.
The American Journal of the Medical Sciences 08/2004; 328(1):57-63. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Twenty-nine HIV-1 infected patients from New Orleans were enrolled as a cohort for this study over a four and one half year period. HIV-1 protease gene (pro) sequences were amplified using DNA isolated from oral tissues (gingival cuff, buccal mucosa, tongue, palate) as well as saliva and peripheral blood mononuclear cells (PBMC). PCR products were directly sequenced using a combination of manual and automated methods, and nucleotide sequences were translated using the universal genetic code. Protein sequences obtained from independent amplifications of a particular patient at a given time were consolidated into a single consensus sequence and compared to HIV-1LAI to determine amino acid replacements. The major findings were: 1) each patient had a signature sequence that probably represented the predominant HIV–1 quasispecies; 2) over periods of 19 to 1673 days mutation patterns remained relatively stable within a given patient; and 3) although nearly 40% of the initial nonsynonymous replacements in the protease signature sequences were mutations known to impart resistance to protease inhibitors (PI), over time patients did not accumulate additional PIR mutations.
Brazilian Journal of Oral Sciences (ISSN: 1677-3217) Vol 3 Num 11. 01/2004;