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

J Oral Pathol Med (2010) 39 : 397–406 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

J Oral Pathol Med (2010) 39 : 28–34
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.     

Risk factors for oral hairy leukoplakia in HIV-infected adults of Brazil

BACKGROUND: Oral hairy leukoplakia (OHL) may be an indicator of the progression of Human Immunodeficiency Virus (HIV)-induced immuno-depression, and the evaluation of risk factors leading to OHL is important in the management of these HIV-infected patients. However, there are few studies that analyze risk factors leading to OHL in the Brazilian population. The aim of this case-control study is to present data about prevalence rates and risk factors leading to OHL in a sample of HIV-infected adults in Brazil. METHODS: This case-control study included 111 HIV-infected patients treated at a clinic for sexually transmitted diseases and HIV. In the initial examinations with dentists, variables were collected from all patients. Diagnosis of OHL was performed in accordance with the International Classification System and cytological features. The Fisher and the chi-squared tests were used for statistical analysis. The proportional prevalence and odds ratio were estimated. RESULTS: Outcome presented a positive, statistically significant association among the presence of OHL and viral load of 3000 copies/mul or greater (P = 0.0001; odds ratio (OR) = 5.8), presence of oral candidiasis (P = 0.0000; OR = 11.1), previous use of fluconazole (P = 0.0000; OR = 24.6), and use of systemic acyclovir (P = 0.032; OR = 4.3). Antiretroviral medication presented a negative, statistically significant association with the presence of OHL (P = 0.002; OR = 8.4). CONCLUSIONS: Prevalence of OHL was 28.8%. Viral load, oral candidiasis, previous use of fluconazole, and systemic acyclovir were determined to be risk factors for OHL. Antiretroviral medication proved to be protective against the development of OHL.     

Co-existence between oral lesions and opportunistic systemic diseases among HIV-infected subjects in Thailand

BACKGROUND: The purpose of this study was to determine whether any relationship exists between the occurrence of oral lesions and opportunistic systemic diseases among HIV-infected subjects. METHODS: A cross-sectional analytical study was performed in two hundred and seventy-eight HIV-infected heterosexual persons and intravenous drug users (IVDUs)(230 males and 48 females, aged 16-65 years, mean 31.9 years). Eighty-six HIV-free subjects from the same population were included as controls (61 males and 25 females, aged 17-63 years, mean age 33.1 years). The following information was recorded for each patient: age, gender, risk group and stage of HIV infection, immune status, medication, systemic disease and presence of oral lesions. RESULTS: Oral candidiasis was the most common oral lesion among HIV-infected individuals (40%), followed by hairy leukoplakia (HL)(26%). The three most common systemic diseases among the subjects were tuberculosis (TB)(53%), cryptococcosis (14%) and Pneumocystis carinii pneumonia (PCP)(11%). Logistic regression analysis revealed a significant association between the occurrence of TB and the presence of oral candidiasis (OR 2.8; 95% CI 1.6-4.8; P < 0.001), and the occurrence of PCP and the presence of HL (OR 2.2; 95% CI 1.1-4.3; P < 0.001). Positive predictive values of any oral lesions and oral candidiasis in predicting TB were 87% (95% CI 73.0-94.6) and 67% (95% CI 51.9-80.0), respectively. CONCLUSIONS: We concluded that oral candidiasis might be used as a clinical marker for TB, and HL for PCP. Recognition of the lesions by health-care providers may indicate the need for more intensive clinical and laboratory monitoring and possibly initiation of prophylaxis against these opportunistic systemic infections.     

口胶粘膜癌前病变及鳞癌角蛋白表达的免疫组化研究

目的研究口腔粘膜标本中角蛋白的表达与分布。方法利用多克隆抗角蛋白抗体A(575)，采用免疫组化技术。结果从正常口腔粘膜，轻、中、重度异常增生到鳞癌角蛋白表达显著增强。A(575)在所有鳞癌标本中均为阳性，但染色强度深浅不一，且随鳞癌分化程度降低而降低，染色弱的病例其临床分期高，更易发生淋巴结转移。结论角蛋白表达的增强在强化上皮细胞中的致癌基因上起作用，这种强化的积累将加速癌前疾病的进展，因此，A575染色可能为预后提供参考依据。     

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

J Oral Pathol Med (2010) 39 195–200 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.     

Oral candidosis and oral hairy leukoplakia as predictors of HAART failure in Brazilian HIV-infected patients

INTRODUCTION: Oral candidosis (OC) and hairy leukoplakia (OHL) are important markers of Human Immunodeficiency Virus (HIV) infection immune status. OBJECTIVES: to evaluate if OC and/or OHL should be considered clinical predictors of immune and virologic failure on HIV-infected Brazilian adults undergoing Highly Active Antiretroviral Therapy (HAART). METHODS: 124 HIV-infected patients who used HAART for a minimum of six months were prospectively evaluated. All of them under-took oral examination and serum CD4+ count and viral load (VL), being divided in two groups, P and A, respectively according to the presence or absence of OC and/or OHL. During a six month period, patients belonging to group A were followed. They were re-examined for new oral lesions. New blood samples were collected and they were subdivided into groups P6 and A6. CD4+ count and VL were compared between groups at baseline and after the six months period. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and relative risk (RR) were obtained in order to assess the accuracy of using OC and OHL as predictors of immune and virologic failure, at baseline and after a six month period. RESULTS: At baseline and after six months, patients with OC and OHL have mean CD4+ count lower and mean VL higher than patients of group A and A6 (p < 0.001). OC had high PPV for immune failure and a moderated PPV for virologic failure. OHL had low PPVs for both measures. DISCUSSION AND CONCLUSIONS: OC and OHL still indicate low serum CD4+ count and high VL, but OC seems to be a better predictor of immune and virologic failure in patients undergoing HAART than OHL.     

细胞角蛋白19mRNA在口腔鳞状细胞癌中表达的研究

目的探讨口腔鳞状细胞癌（OSCC）患者癌组织中细胞角蛋白（CK）19 mRNA的变化和其发生的可能机制以及CK19 mRNA检测的临床应用价值。方法收集未接受过放疗和化疗的20例OSCC患者的手术标本（包括癌组织20块、癌旁组织20块和颈清扫的淋巴结43枚）,采用荧光定量聚合酶链式反应（FQ-PCR）法检测组织内CK19 mRNA的表达,比较CK19 mRNA在上述组织中的相对表达量。结果CK19 mRNA在OSCC癌组织内表达比其在正常口腔黏膜内表达高1.85倍,比其在癌旁组织内表达高1.66倍。9例患者颈清扫淋巴结内CK19 mRNA表达阳性,阳性率为45%（9/20）,而9例患者的22枚淋巴结中CK19 mRNA表达阳性率是81.8%（18/22）,占20例患者43枚淋巴结的41.9%（18/43）。淋巴结CK19 mRNA阳性患者的癌组织与癌旁组织和正常口腔黏膜的表达量比CK19 mRNA阴性患者低。结论CK19 mRNA在OSCC癌组织中的表达高于其在癌旁组织和正常口腔黏膜内的表达,可能是由于癌组织中CK19的合成明显增加所致。淋巴结中CK19 mRNA的表达可以作为检测OSCC淋巴结微转移的指标之一,运用FQPCR法检测淋巴结中CK19 mRNA的表达来检测OSCC的淋巴结微转移比普通病理法检测更灵敏。     

Oral Candida in HIV-infected heterosexuals and intravenous drug users in Thailand

The objectives of this study were to determine levels of oral yeasts in Thai people at different stages of HIV infection compared with HIV-negative controls, to identify factors associated with the levels of oral Candida, and to determine whether the levels of the organism can be used as a predictive clinical marker in HIV-infected individuals. One hundred and eighty HIV-infected heterosexual persons and intravenous drug users (IVDUs) were enrolled (152 men, 28 women). Eighty-three HIV-free subjects from the same population were included as controls (48 men, 35 women). Oral yeasts were isolated in 103 HIV-infected subjects (57.2%) and 36 HIV-negative controls (43.3%). The mean number of colony forming units (CFU) of oral Candida in the first group was 1.9x10(4) CFU/ml (range 2.2x10(2)-4.0x10(6) CFU/ml), which was significantly different statistically when compared with 1.7x10(3) CFU/ml (range 4.0x10(2)-1.2x10(5) CFU/ml) in the control group (P=0.0000). The following factors are significantly associated statistically with the levels of oral Candida among the subjects (P<0.05): age, stage of HIV infection, total number of lymphocyte cell count, risk group, nutritional status, general health status, weight loss, type of oral lesions and number of oral lesions and number of sites affected. The study revealed that HIV serostatus, stage of HIV infection, and the occurrence of oral lesions among HIV-infected subjects may be predicted by the levels of oral Candida (P<0.05). By using a cut-off point of 2.0x10(3) CFU/ml, the sensitivity and predicitve values of the level of oral Candida on the HIV serostatus was higher than that based on the culture positivity results alone, although the specificity was similar. These findings suggest that, in conjunction with some other clinical signs and laboratory findings, the levels of oral Candida may be used as a predictive marker of disease in HIV infection.     

Oral manifestations of HIV infection in patients receiving highly active antiretroviral therapy (HAART) in Bahia, Brazil

Objectives: We investigated the oral manifestations of HIV‐infected patients in Salvador, Brazil, and their relationship to immunologic, sociodemographic, and therapeutic factors. Methods: This was a cross‐sectional study that used data from adult patients' medical records in the dentistry service of the AIDS Reference Center in Salvador, Brazil. We reviewed the patients' records to collect information concerning oral health status and data on socioeconomic status, immunologic status, and treatment. Results: A total of 993 patients were included in the study, of whom 473 (47.6 percent) were male. Approximately 5.5 percent of the patients presented with any oral lesions. Oral lesions were the most common in the patients with fewer than 350 CD4+T lymphocytes (8.4 percent) and with viral loads greater than 10,000 copies (8.3 percent). Conclusions: Our study shows that lesions are more common in patients with advanced immune suppression and low level of schooling. Oral candidiasis and angular chelitis were the most common lesions seen.     

Risk factors associated with oral lesions in HIV-infected heterosexual people and intravenous drug users in Thailand

This study aimed to identify factors associated with the presence of oral lesions in HIV-infected individuals in Thailand, to determine the influence of gender and route of HIV transmission on the prevalence of the lesions, and to investigate whether total lymphocyte cell counts can be used as a serologic marker to predict the occurrence of oral lesions. Two hundred and seventy-eight HIV-infected heterosexual persons and intravenous drug users (IVDUs) were enrolled (230 males, 48 females). Eighty-six HIV-free subjects from the same population were included as controls (61 males, 25 females). Oral candidiasis was the most common oral lesion among HIV-infected individuals (39.6%), followed by hairy leukoplakia (HL) (26.3%), exfoliative cheilitis (18.3%), and linear gingival erythema (LGE) (11.5%). Odds ratios (ORs) for factors associated with the presence of oral lesions were as follows for advanced HIV disease defined by clinical status: symptomatic stage [OR= 18.6; 95% confidence interval (CI) 7.3-47.2], AIDS stage [OR 7.3; 95% CI 3.4-15.7] and laboratory investigation of total number of lymphocyte cell counts of 1,000-2,000 cell/mm3 [OR 2.7; 95% CI 1.4-5.1] and <1,000 cell/mm3 [OR 4.0; 95% CI 2.3-7.0], alcohol consumption [OR 3.4; 95% CI 1.3-9.1], and poor oral health [OR 1.7; 95% CI 1.0-2.9]. Men were significantly more likely to have oral lesions than women. No statistically significant difference in the presence of oral lesions was observed between heterosexuals and IVDUs. This study should help predict the risk of acquiring various types of oral lesions, given that the person is exposed to multiple risk factors compared to another who is not exposed to these factors.     

Cytomegalovirus associated oral ulcerations in HIV-infected patients

Oral ulcerations associated with disseminated cytomegalovirus (CMV) infection were observed in four patients with AIDS manifestations showing low CD4 counts. Virus cultures of urine and saliva samples were positive for CMV in all cases. The lesions were characterized by a punched-out appearance, non-indurated borders, low bleeding tendency and lack of inflammatory wall. Light microscopy revealed granulation tissue containing "owl's eye" like cells in all specimens. Presence of CMV was confirmed by immunohistochemistry and in situ hybridization. The ulcerations were infiltrated with T-lymphocytes of the helper, suppressor and cytotoxic subset, most were positive for HLA DR. Despite the local invasion with immunocytes and high serum titers of serum antibodies the patients experienced progressive CMV disease.     

Changes in cytokeratin expression during the development of the human oral mucosa

The changes in cytokeratin expression by the developing oral mucosa of 10 to 23-week-old human fetuses were studied by indirect immunofluorescence using a panel of 15 monoclonal antibodies. The lining and masticatory mucosae were incompletely differentiated in 10-wk fetuses, since they expressed identical patterns of cytokeratins (CK 4, 5, 8, 13, 18, 19 and probably CK 14, 16, 17) very similar to that of adult alveolar mucosa. The main difference was the presence of cytokeratins 8, 18 and 19 in embryonic tissues. Cytokeratins 1, 2, 10 and 11 began to appear in gingival and hard palate epithelium from wk 11, predicting the differentiation of the masticatory mucosa by wk 16. The patterns of cytokeratin expression in the 23-wk fetus in the lining and masticatory mucosae appear to be different. In lining mucosa, the only difference from the 10th wk is a decrease in cytokeratins 8, 18 and 19, whereas the pattern of cytokeratin expression in masticatory mucosa (CK 1, 2, 4, 5, 8, 10, 11, 13, 18, 19 and probably CK 14, 16 and 17) is now very near that of adult gingiva. This pattern appears, as in the adult, to be similar to that of the epidermis in the same period.     

Oral white patches in a national sample of medical HIV patients in the era of HAART

OBJECTIVES: Several types of HIV-related oral mucosal conditions have been reported to occur during the course of HIV disease progression. Of these, few may be manifested as 'white' lesions and many are noticeable to the patient. This paper examines the relationships between social, behavioral and medical aspects of HIV infection and reporting an occurrence of oral white patches (OWP) by HIV-infected patients. METHODS: The subjects are participants in all three interviews in the HIV Cost and Services Utilization Study (HCSUS). The subjects were selected using a three-stage probability sampling design. The multivariate analysis is based on 2109 subjects with nonmissing binary outcome variable for all three waves representing a national sample of 214 000 individuals. The multivariate model was fitted using generalized estimating equations (GEE) by implementing the XTGEE command in STATA. RESULTS: We estimate that 75 000 persons (35%) reported at least one incident of OWP, of these 14 000 reported having OWP during all three interviews, and that the rate of reporting declined over the three HCSUS waves. The multivariate analysis showed seven variables that were significant predictors of at least one report of OWP. CONCLUSIONS: Compared with persons on HAART therapy, patients on other regimens or taking no antiviral medications were 23-46% more likely to report an incident of OWP. Compared with whites, African Americans were 32% less likely to report OWP, while current smokers were 62% more likely than nonsmokers. Being diagnosed with AIDS and having CD4 counts less than 500 significantly increased the likelihood of reporting OWP.     

细胞角蛋白17在口腔鳞癌中的表达

目的 研究细胞角蛋白17(CK17)在口腔鳞癌中的表达,以期为口腔鳞癌的诊断和预防提供依据.方法 分别采用实时定量聚合酶链反应、免疫印迹方法和免疫组化方法检测口腔黏膜上皮体外癌变模型、口腔鳞癌细胞株及30例原发口腔鳞癌标本中的CKl7 mRNA及蛋白质的表达.结果 与永生化HIOEC细胞相比,CK17 mRNA在HB5...     

Ultrastructural findings in oral hyperpigmentation of HIV-infected patients

Oral hyperpigmentation has been observed in six HIV-infected patients, in two of whom systemic medication (ketokonazole, clofazimine) was supposed to be etiologically involved. Histologically, pigment was found in epithelial basal cells and particularly in subepithelial connective tissue. Ultrastructurally, the presence of premature melanosomes in subepithelial keratinocytes was of interest. Stimulation of melanocytes during HIV infection may occur in association with immunopathologic changes in the oral mucosa.     

Fluconazole resistant oral candidiasis in HIV-infected patients

OBJECTIVE: To evaluate the risk factors associated with the emergence of fluconazole resistant Candida spp. in HIV-infected patients with oral candidiasis. METHODS: Candida spp. were isolated from oral swabs and tested in vitro for resistance to fluconazole. The factors potentially correlated with vazole-resistent Candida spp. infections were investigated. RESULTS: Fifty-one out of 118 patients (43%) with oral candidiasis had fluconazole resistant Candida spp. The following factors were significantly associated with the development of fluconazole resistance: (1) more than five episodes of oral candidiasis in the previous year (P < 0.001); (2) fluconazole therapy in the previous 6 months (P < 0.001); (3) C3 category of HIV infection (P< 0.001); and (4) low number of TCD4⁺ cells (<50 mm³, P = 0.002). According to multivariate analysis, previous therapy with fluconazole was the only risk factor that independently influenced the development of Candida spp. resistance (P = 0.003). CONCLUSIONS: The prophylaxis and therapy of mild fungal infections in HIV-infected patients, which may lead to azole resistance, should be carefully considered.