Wipawee Nittayananta

Effects of long-term use of HAART on oral health status of HIV-infected subjects

BACKGROUND The aim of this study was to determine the effects of long-term use of highly active antiretroviral therapy (HAART) on oral health status of HIV-infected subjects. METHODS Oral examination and measurement of saliva flow rate of both unstimulated and wax-stimulated whole saliva were performed in HIV-infected subjects with and without HAART, and in non-HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long-term use of HAART on oral health status of HIV-infected subjects. RESULTS One hundred and fifty-seven HIV-infected subjects - 99 on HAART (age range 23-57 years, mean 39 years) and 58 not on HAART (age range 20-59 years, mean 34 years) - and 50 non-HIV controls (age range 19-59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV-infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short-term HAART (P < 0.01). The subjects with long-term HAART were found to have a greater risk of having oral lesions than those with short-term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05). CONCLUSION We conclude that long-term HAART has adverse effects on oral health status of HIV-infected subjects.

Hyposalivation, xerostomia and oral health status of HIV-infected subjects in Thailand before HAART era.

BACKGROUND The aims of this study were to determine hyposalivation, xerostomia, and oral health status of HIV-subjects in Thailand before highly active antiretroviral therapy era. METHODS Oral examination and measurement of saliva flow rate of both unstimulated and wax-stimulated whole saliva were performed in 135 subjects (56 HIV-subjects, mean age: 34.5 years, and 79 non-HIV controls, mean age: 29.5 years). Presence of oral candidiasis, cervical root caries, and number of existing teeth were recorded. Microbiological investigation of oral Candida was conducted using oral rinse technique. Risk factors associated with hyposalivation and xerostomia were analysed. RESULTS The unstimulated flow rates in HIV-subjects and non-HIV controls were 0.19 and 0.33 ml/min (P = 0.0024). For stimulated flow rates, the corresponding figures were 1.45 and 1.62 ml/min (P = 0.31). The unstimulated flow rate was significantly higher in the asymptomatic HIV-subjects: 0.17 ml/min, when compared with the symptomatic/AIDS group 0.11 ml/min (P = 0.003). No significant difference between the groups could be found with respect to stimulated flow rate. Hyposalivation was significantly associated with the colony forming unit of Candida. Smoking and alcohol consumption were significantly associated with hyposalivation, but not xerostomia. The following factors were significantly associated with both hyposalivation and xerostomia; sex, stage of HIV infection, risk group of HIV infection, systemic disease, and medication use. CONCLUSIONS Salivary flow rate of HIV-subjects in Thailand was affected by HIV infection. The rate was significantly decreased with advanced stage of the disease. Various factors including medication use were associated with hyposalivation and xerostomia among the subjects.

Urban legends series: oral manifestations of HIV infection

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.

Ellagic acid modulates the expression of oral innate immune mediators: potential role in mucosal protection.

BACKGROUND Ellagic acid (EA) found in various fruits such as pomegranates, blackberries, raspberries, strawberries, and walnuts has different pharmacological functions including antioxidant, antitumor, antiallergic, anti-inflammatory, antibacterial, and antiviral activities. It is not known, however, if EA could enhance mucosal innate immunity. Our goal was to determine the effects of EA on the expression of innate immune mediators produced by oral epithelial cells. METHODS Culture of primary human gingival epithelial cells (HGEs) was performed in duplicate, and after the primary HGEs had been treated with EA at a concentration ranging from 12.5 to 100 μM for 18 h the cells and supernatants were harvested. The expression of innate immune mediators including human β-defensin 2 (hBD2), secretory leukocyte protease inhibitor (SLPI), and various cytokines and chemokines was measured at both transcriptional and translational levels by using quantitative real-time PCR, ELISA, and Luminex assay. RESULTS In the presence of EA, the expression of hBD2-and SLPI mRNA was 3.7-folds and 2.6-folds greater than untreated controls, respectively, and consistent with their secreted protein levels. For cytokines and chemokines, increased expression of RANTES, IL-2, and IL-1β was found in response to EA. In contrast, EA decreased the expression of IL-6, IL-8, and TNF-α. CONCLUSIONS This study demonstrated that oral innate immunity is affected by EA found in fruits. Thus, it may play some roles in mucosal innate immunity. The potential of EA for modulating the innate immune mediators may lead to developing a new topical agent to treat and/or prevent immune-mediated oral diseases.

A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis-free period in HIV infection

OBJECTIVE To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis. SUBJECTS AND METHODS A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22-52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed. RESULTS The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034). CONCLUSIONS Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings.

Mode of HIV transmission associated with risk of oral lesions in HIV-infected subjects in Thailand

BACKGROUND The aim of this study was to determine if route of human immunodeficiency virus (HIV) transmission is associated with the risk of oral lesions in HIV-infected subjects in Thailand. METHODS A cross-sectional study was performed in 186 HIV-infected heterosexuals (aged 21-65 years, mean 32 years), and 82 HIV-infected intravenous drug users (IVDUs) (aged 16-50 years, mean 30 years). The following information was recorded: route of HIV transmission, total lymphocyte cell counts, weight, smoking habit, alcohol consumption, medications, presence of denture, plaque index, and presence of oral lesions. The association between mode of HIV transmission and the risk of oral lesions among the subjects was determined by multiple logistic regression analysis. RESULTS Oral lesions were found in 138 HIV-infected heterosexuals (75%) and in 37 HIV-infected IVDUs (46%). Oral candidiasis (OC) was the most common lesion among both groups (44% vs. 28%), followed by hairy leukoplakia (HL) (33% vs. 10%). Multiple logistic regression analysis showed a significant association between mode of HIV transmission and the risk of oral lesions after controlling for the total lymphocyte cell counts and other confounding factors [OR 3.1; 95% CI 1.5-6.4; P = 0.002]. OC was significantly associated with heterosexual route of HIV transmission [OR 2.4; 95% CI 1.2-4.7; P = 0.014]. Similar association was also observed with HL [OR 3.7; 95% CI 1.5-9.1; P = 0.004]. CONCLUSIONS Mode of HIV transmission is associated with the risk of oral lesions in HIV-infected subjects in Thailand. Further studies should be performed to determine if the risk of oral lesions is associated with differences in HIV-subtypes.

Impacts of HIV infection and long-term use of antiretroviral therapy on the prevalence of oral human papilloma virus type 16

BACKGROUND The objectives of this study were to determine (i) the prevalence and the copy numbers of oral human papilloma virus type 16 (HPV-16) in HIV-infected patients compared with non-HIV controls, and (ii) the effects of antiretroviral therapy (ART) and its duration on the virus. METHODS A cross-sectional study was carried out in HIV-infected patients with and without ART and in non-HIV controls. Saliva samples were collected, and the DNA extracted from those samples was used as a template to detect HPV-16 E6 and E7 by quantitative polymerase chain reaction. Students t-test and ANOVA test were performed to determine the prevalence rates among groups. RESULTS Forty-nine HIV-infected patients: 37 on ART (age range, 23-54 years; mean, 37 years), 12 not on ART (age range, 20-40 years; mean, 31 years), and 20 non-HIV controls (age range, 19-53 years; mean, 31 years) were enrolled. The prevalence of oral HPV-16 infection and the copy numbers of the virus were significantly higher in HIV-infected patients than in non-HIV controls when using E6 assay (geometric mean = 10696 vs. 563 copies/10(5) cells, P < 0.001), but not E7 assay. No significant difference was observed between those who were and were not on ART. Long-term use of ART did not significantly change the prevalence of oral HPV-16 infection and the copy numbers of the virus (P = 0.567). CONCLUSION We conclude that the prevalence of oral HPV-16 infection and the copy numbers of the virus are increased by HIV infection. Neither the use of ART nor its duration significantly affected the virus.

Oral human β-defensin 2 in HIV-infected subjects with long-term use of antiretroviral therapy

BACKGROUND The objectives of this study were to determine (i) oral hBD2 expression in HIV-infected subjects compared with non-HIV controls, (ii) the expression of oral hBD2 in HIV-infected subjects with antiretroviral therapy (ART) compared with those without ART, and (iii) factors associated with the expression of oral hBD2. METHODS Oral examination and punched biopsy on buccal mucosa were performed in HIV-infected subjects with and without ART, and non-HIV individuals. The expression of hBD2 mRNA was determined by quantitative real-time PCR. Saliva samples of both un-stimulated and stimulated saliva were collected and analyzed for hBD2 levels using ELISA. Students t-test and nonparametric multi-way ANOVA test were used for comparison of measurements between or among groups. RESULTS One hundred and fifty-seven HIV-infected subjects were enrolled: 99 on ART (age range, 23-57 years; mean 39 years), 58 not on ART (age range, 20-59 years; mean 34 years), and 50 non-HIV controls (age range, 19-59 years; mean 36 years). The most common ART regimen was two nucleoside reverse transcriptase inhibitors + one non-nucleoside reverse transcriptase inhibitor. Salivary levels of hBD2 were significantly increased in HIV infection (P < 0.001). The levels of hBD2 in stimulated saliva were also found to be significantly different between HIV-infected subjects who were and were not on ART (P < 0.001). No significant difference was observed with the expression of hBD2 mRNA. CONCLUSION Oral innate immunity is affected by HIV infection and use of ART. Salivary hBD2 levels may be the useful biomarkers to monitor those on long-term ART who are at risk of developing oral infections and malignant transformation.

HIV Type 1 Fails to Trigger Innate Immune Factor Synthesis in Differentiated Oral Epithelium

The oral mucosa is relatively resistant to human immunodeficiency virus type 1 (HIV-1) transmission. The mechanisms contributing to this resistance remain incompletely understood, but may include HIV-induced synthesis of innate immune factors. We used fully differentiated oral epithelium as a surrogate for the oral mucosa in vivo, exposed it to X4- and R5-tropic HIV-1 in culture, and quantified mRNA expression of six innate immune factors. Neither virus increased expression of human beta defensin 2 (hBD-2) mRNA over supernatants from uninfected lymphoblast controls. HIV-1 also failed to induce mRNA of four additional innate immunity-related genes. Similar results were obtained with oral monolayer epithelial cells. Interestingly, the X4-tropic virus inhibited mRNA expression of hBD-2, and of three of the other factors, at higher dosages in the differentiated oral epithelium but not the monolayers. The failure of HIV-1 to induce innate immune factors in the differentiated epithelium was not due to a lack of tissue penetration, as we detected fluorescence-tagged virions up to 30 mum deep from the apical surface. HIV-1 does not trigger de novo innate immune factor synthesis in oral epithelium, pointing to the role of a constitutive innate immunity for protection against HIV-1 in the oral cavity.

Effects of long-term use of antiretroviral therapy on the prevalence of oral Epstein–Barr virus

BACKGROUND The objectives of this study were to determine (i) the prevalence of oral Epstein-Barr virus (EBV) in HIV-infected subjects compared to non-HIV controls and (ii) the effects of long-term use of antiretroviral therapy (ART) on the prevalence of oral EBV. METHODS A cross-sectional study was performed in HIV-infected subjects with and without ART, and non-HIV individuals. DNA in saliva samples was extracted and used as a template to detect EBV BamH1W and EBNA1 by quantitative polymerase chain reaction. Student t-test and ANOVA test were performed to determine the prevalence rates among groups. RESULTS Forty-nine HIV-infected subjects: 37 on ART (age range 23-54 year, mean 37 year), 12 not on ART (age range 20-40 year, mean 31 year), and 20 non-HIV controls (age range 19-53 year, mean 31 year) were enrolled. The numbers of EBV BamH1W in saliva were found to be significantly higher in HIV-infected subjects than non-HIV controls (80% vs. 20%, mean = 12118 vs. 134 copies/10(5) cells, P < 0.001). HIV-infected subjects who were on ART had significantly lower numbers of EBV BamH1W than those who were not (mean = 4102 vs. 138613 copies/10(5) cells, P = 0.011). The numbers were significantly lower in those who received long-term ART compared with short-term (mean = 1401 vs. 11124 copies/10(5) cells, P = 0.034). No significant difference was observed between the groups when using EBNA1 primers. CONCLUSIONS Prevalence of oral EBV was significantly higher in HIV-infected subjects than non-HIV-controls. The numbers of the virus were significantly decreased by ART. Long-term use of ART did not increase oral EBV.