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New England Journal of Medicine 02/2010; 362(10):872-3. · 53.30 Impact Factor
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Journal of Dental Research 04/2007; 86(3):202-3. · 3.49 Impact Factor
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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.
JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2006; 42(5):578-83. · 4.43 Impact Factor
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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. · 2.55 Impact Factor
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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. · 2.87 Impact Factor
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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. · 2.46 Impact Factor
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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. · 4.16 Impact Factor
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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. · 6.41 Impact Factor
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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. · 2.41 Impact Factor
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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. · 1.39 Impact Factor
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ABSTRACT: Periodontal disease has been previously associated with human immunodeficiency virus (HIV) infection, and HIV infection has been considered a modifier of periodontal disease. The aim of this study was to report the prevalence and severity of periodontal disease in a population of HIV-positive individuals and to investigate the association between clinical periodontal indices and the stage of HIV disease, as expressed by CD4 cell counts.
Thirty-nine male HIV-positive patients were recruited and a medical history was taken. To evaluate periodontal disease, probing depth (PD), attachment level loss (AL), bleeding index (BI), and modified gingival index (MGI) were recorded. Associations between the above indices and CD4 counts were examined.
Immunocompromised patients (with CD4 cell counts < 200 cells/microl) showed significantly lower BI and fewer sites with PD and AL > 4 mm compared to patients with CD4 cell counts > 200 cells/microl. When patients with CD4 counts < 500 cells/microl were considered alone, a correlation was observed between CD4 cell counts and BI (r2 = 0.1617, P = 0.0463), MGI (r2 = 0.2123, P = 0.0204), and number of sites with AL > 4 mm (r2 = 0.1469, P = 0.056).
Severely immunocompromised HIV-positive patients showed less severe gingival inflammation than expected. Patients with CD4 cell counts > 500 cells/microl showed no association between CD4 cell count and periodontal indices.
Journal of Periodontology 10/2003; 74(9):1336-41. · 2.60 Impact Factor
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ABSTRACT: Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most frequent opportunistic fungal infection in human immunodeficiency virus (HIV)-positive persons. Although Th1-type CD4(+) T cells are considered important for host defense against mucosal C. albicans infections, there is a paucity of information regarding the presence and/or role of T cells in OPC lesions. In pursuit of this, initial chromophore immunohistochemical studies showed a majority of CD8(+) rather than CD4(+) cells equally distributed throughout the buccal mucosa of OPC(-) persons (HIV(-) or HIV(+)), irrespective of blood CD4(+) cell numbers. In contrast, CD8(+) cells in lesions from HIV(+) OPC(+) persons were in significantly higher numbers and concentrated at the lamina propria-epithelium interface, a considerable distance from the Candida at the outer epithelium. Dual fluorescence and confocal microscopy confirmed that the majority of CD8(+), but not CD4(+), cells were T cells by the presence or absence, respectively, of CD3 on each cell type. These results suggest that CD8(+) T cells may be important for oral host defense against OPC, especially when CD4 cell numbers are reduced, with a potential CD8 cell-specific dysfunction associated with susceptibility to OPC.
Infection and Immunity 03/2003; 71(2):956-63. · 4.16 Impact Factor
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ABSTRACT: Objectives: The purpose of this retrospective study was to determine the seropositivity of the rapid plasma reagin (RPR) in a dental school patient population. Methods: Blood was drawn on 20,844 subjects registering for treatment at the Louisiana State University School of Dentistry. All subjects who are admitted to the dental school are submitted to RPR screening (Macro-Vue-RPR Card, Becton Dickinson), blood indices, and serum chemistries. Venereal Disease Research Laboratory (VDRL), microhemagglutination assay for Treponema pallidum (MHA-TP) and/or fluorescent treponemal absorption test for Treponema pallidum (FTA-ABS) were also run on the positive RPR results. Results: Two hundred seventy-nine (1.34%) of the 20,844 were RPR-positive. Sixty-two subjects (0.30%) of this total population from the RPR-positive findings were nonreactive (biological false positives or BFP) to the MHA-TP and FTA-ABS. This left 217(1.04%) subjects of the 20,844 screened who were seropositive on both the RPR and the FTA-ABS or MHA-TP. Conclusions: Since this study has not been performed in a dental school patient population setting, comparison with other institutions is difficult. The authors agree that routine RPR testing is helpful and cost effective to detect patients possibly infected with Treponema pallidum in a large patient population.
Journal of Public Health Dentistry 02/2003; 63(1):61 - 63. · 1.19 Impact Factor
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ABSTRACT: The purpose of this retrospective study was to determine the seropositivity of the rapid plasma reagin (RPR) in a dental school patient population.
Blood was drawn on 20,844 subjects registering for treatment at the Louisiana State University School of Dentistry. All subjects who are admitted to the dental school are submitted to RPR screening (Macro-Vue-RPR Card, Becton Dickinson), blood indices, and serum chemistries. Venereal Disease Research Laboratory (VDRL), microhemagglutination assay for Treponema pallidum (MHA-TP) and/or fluorescent treponemal absorption test for Treponema pallidum (FTA-ABS) were also run on the positive RPR results.
Two hundred seventy-nine (1.34%) of the 20,844 were RPR-positive. Sixty-two subjects (0.30%) of this total population from the RPR-positive findings were nonreactive (biological false positives or BFP) to the MHA-TP and FTA-ABS. This left 217 (1.04%) subjects of the 20,844 screened who were seropositive on both the RPR and the FTA-ABS or MHA-TP.
Since this study has not been performed in a dental school patient population setting, comparison with other institutions is difficult. The authors agree that routine RPR testing is helpful and cost effective to detect patients possibly infected with Treponema pallidum in a large patient population.
Journal of Public Health Dentistry 02/2003; 63(1):61-3. · 1.19 Impact Factor
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ABSTRACT: Approximately 500 HIV-1 protease gene (pro) sequences were obtained from oral tissues (gingival cuff, buccal mucosa, tongue, palate) as well as saliva and peripheral blood mononuclear cells (PBMC) of 80 HIV-1 positive patients by nested amplification and manual sequencing of PCR products. By visual inspection each patient in this study exhibited a unique sequence profile. HIV-1 pro sequences obtained from patients with oropharyngeal candidiasis (OPC(+) patients) had significantly higher numbers of mutations than sequences from OPC(-) patients, but OPC(+) patients were no more likely to accumulate protease inhibitor resistance mutations than OPC(-) patients. Although the sequences for each patient were predominantly consistent between PBMC and oral tissues, approximately 10% of the patients demonstrated tissue specificity, and patients that demonstrated tissue specificity tended to be OPC(+). Furthermore, HIV-1 pro sequences derived from OPC lesions demonstrated unique mutations in approximately 30% of the patients who provided paired OPC(+/-) samples of the same tissue type. These data provide evidence for minimal compartmentalization of HIV-1 in oral tissues, yet some patients demonstrate minor variation between the HIV-1 pro sequences obtained from an OPC lesion and those obtained from a non-lesion site of similar tissue.
Virus Research 09/2002; 87(2):97-106. · 2.94 Impact Factor
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ABSTRACT: Oropharyngeal candidiasis (OPC) is a common oral opportunistic infection among human immunodeficiency virus (HIV)-positive individuals. Although most cases of OPC correlate with reduced systemic levels of CD4(+) T cells, the role of humoral immunity in protection against mucosal candidiasis, including OPC, remains questionable. In the present study, a comprehensive analysis of saliva from 33 HIV-negative and 68 HIV-positive individuals, stratified by OPC status and peripheral CD4(+) cell count, was conducted to measure levels of total and Candida-specific immunoglobulin A(IgA) and IgG antibodies, including subclasses and secretory IgA. Despite changes in total immunoglobulin levels, when levels of Candida-specific antibodies were normalized to total protein or total immunoglobulin of the corresponding isotype, no distinct differences in IgG (including subclasses), IgA (including subclasses), or secretory IgA levels were seen, regardless of HIV status, OPC status, or CD4(+) cell count. These data suggest that when a complete repertoire of antibodies is evaluated, with appropriate normalization of data, there is no evidence of appreciable changes in levels of Candida-specific antibodies in saliva that would account for the prevalence of OPC among HIV-positive individuals.
The Journal of Infectious Diseases 06/2002; 185(9):1269-76. · 6.41 Impact Factor
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ABSTRACT: HIV-1 protease gene sequences were obtained from peripheral blood, saliva or oral tissues of 35 HIV+ patients using nested amplification and manual sequencing of PCR products. Of the 35 HIV+ patients 9 had clinical oropharyngeal candidiasis (OPC) while 26 did not, and only 4 patients were on protease inhibitor (PI) therapy. These patients were collected prior to major use of HAART therapy in New Orleans, Louisiana. Analysis of 172 amino acid sequences revealed unique patterns of mutation that were in most cases independent of the type of cell from which DNA was isolated and were, instead, primarily dependent on the individual patient. Principal component analysis indicated that approximately 50% of the variance of the amino acid replacements could be explained by patterns of change seen in only five patients. Significantly, 4 of these 5 patients were OPC+ indicating that patients with OPC are more likely to express a principal mutation pattern than patients without OPC (p = 0.002, Chi square). Dendrograms revealed that these five patients clustered separately from each other and from HIV-1LAI suggesting that principal mutation patterns as well as OPC are independent of viral evolution. In conclusion, prior to widespread use of PI therapy to combat HIV-1, patients with OPC exhibited unique patterns of amino acid replacements within the HIV-1 protease.
Brazilian Journal of Oral Sciences (ISSN: 1677-3217) Vol 3 Num 9.
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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.
