Modulation of the orodigestive tract microbiome in HIV-infected patients.

More than 37 million people are living with human immunodeficiency virus 1 (HIV), and more people than ever received lifesaving antiretroviral therapy worldwide. HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the GI microbiome and its association with host immune activation. The data indicated that the microbiome was different in HIV-positive and HIV-negative individuals. The initial sequence analysis of saliva indicated that there were major differences in the phyla of Bacteroidetes, Firmicutes, Proteobacteria, and TM7. Phylum Tenericutes was only seen in HIV-positive saliva. At the family level, we identified differences in Streptococcacea, Prevotellaceae, Porphyromonadaceae, and Neisseriaceae, whereas data from various sites in GI tract indicated that Prevotella melaninigencia, Fusobacterium necrophorum, Burkholderia, Bradyrhizobium, Ralstonia, and Eubacterium biforme were predominant but differentially present at various sites. Furthermore, there was a decrease in seven proteins associated with the alternative complement pathway and an increase in 6 proteins associated with the lectin and classical complement pathways. The correlation with a shift in complement pathways suggests that compromised immunity could be responsible for the observed dysbiosis in the GI microbiome.

Mucosal fluids and biomarkers of clinical disease: workshop 3B.

Diagnostic tests for a range of oral and systemic diseases using fluids sampled from the mouth are under intense investigation and are increasingly being used. Methods exist for identification of HIV antibody and nucleic acid and for other viral infections of the mouth, such as Kaposi sarcoma herpes virus or human herpesvirus-8, which may coexist with HIV. A number of commercial test kits are available, with variable evidence of sensitivity, specificity, and utility. There is intense research on sophisticated but potentially facile handheld in-office devices for many disease markers. Challenges to their uptake require well-designed studies on their practical reliability and utility, with appropriate controls. A range of ethical, social, and political issues need to be addressed in such studies.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS). DESIGN: Longitudinal cohort study. SUBJECTS AND METHODS: A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands. MAIN OUTCOME MEASURES: Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no). RESULTS: Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated (P = 0.01) and stimulated (P = 0.0004) salivary flow rates as well as salivary gland enlargement (P = 0.006) as compared with non-PI based HAART. CONCLUSIONS: PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.

The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV-positive and at-risk women.

The association of xerostomia and salivary gland hypofunction with HIV infection has been established for men but not for women. We investigated the prevalence of these conditions in a national cohort (n = 733) of HIV-positive and at-risk HIV-negative women. Participants in this prospective cross-sectional study were recruited from the Women's Interagency HIV Study (WIHS) at five outpatient USA clinics. Xerostomia was assessed based on "yes" responses to a dry-mouth questionnaire. Samples of unstimulated whole and chewing-stimulated whole saliva were collected under standardized conditions. The major salivary glands were also evaluated clinically. The prevalence of dry-mouth complaint, the absence of saliva upon palpation, and zero unstimulated whole saliva (flow rate = 0 mL/min) were significantly (p = 0.001) higher in HIV-positive women. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher in HIV-positive women vs. HIV-negative women (OR = 2.86; 95% CI, 1.23 to 6.63). Significant (p = 0.03) univariate association was found between zero unstimulated whole saliva and CD4 counts. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher for HIV-positive women with CD4 < 200 compared with those with CD4 > 500 (OR = 2.61; 95% CI, 1.17 to 5.85). Chewing-stimulated flow rates were not significantly different between seropositive and seronegative women. The prevalence of xerostomia and salivary gland hypofunction appears to be significantly higher in HIV-positive women relative to a comparable group of at-risk seronegative women. Immunosuppression levels measured by CD4 cell counts are significantly associated with xerostomia and salivary gland hypofunction in a population of HIV-positive women.

Dental caries in HIV-seropositive women.

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.

The accurate diagnosis of oral lesions in human immunodeficiency virus infection. Impact on medical staging.

OBJECTIVE: To compare identification of oral candidiasis (OC) and oral hairy leukoplakia (OHL) by medical examiners and oral/dental examiners and to assess the impact of these diagnoses on the medical staging of the human immunodeficiency virus (HIV). DESIGN: Retrospective analysis of data collected by medical and oral/dental examiners at the baseline examination of a prospective study. SETTING: Homosexual men and men and women who were parenteral drug users residing in New York City, enrolled in a longitudinal cohort study. SUBJECTS: A total of 245 individuals participated in this study. MAIN OUTCOME MEASURES: The diagnoses of OC and OHL as recorded in the medical and oral/dental charts were analyzed retrospectively for the same medical and oral/dental evaluation visits. The medical staging of HIV infection based on that evaluation was analyzed concomitantly. RESULTS: Among homosexual men, the oral/dental examiners diagnosed OC in 11% of the individuals and the medical examiners in 4%. In the same cohort, OHL was diagnosed by the oral/dental examiners in 14% of the individuals and by the medical examiners in 8%. Among the parenteral drug users the oral/dental examiners diagnosed OC in 29% of the individuals while the medical examiners made this diagnosis in 11%. In the same cohort, OHL was diagnosed by the oral/dental examiners in 9% of the individuals and by the medical examiners in 2%. The OC and OHL diagnoses affected the medical staging of 12% of the HIV-positive homosexual men and of 22% of the HIV-positive parenteral drug users. Forty percent of the HIV-positive homosexual men and 79% of the HIV-positive parenteral drug users with stage-defining oral lesions were not properly identified by the medical examiners. CONCLUSIONS: Specific training and a comprehensive oral examination have a significant impact on the diagnoses of OC and OHL, and on the medical staging of individuals with HIV infection.

A 12-month study of the efficacy of a pre-brushing rinse in plaque removal.

A 12-month clinical trial was conducted to compare the effectiveness of a pre-brushing rinse (PBR) in plaque removal with that of water. Four groups participated in the study; group 1 (test group) rinsed with PBR before brushing; group 2 rinsed with plain tap water; group 3 brushed only; and group 4 rinsed with sterile water (same color as the PBR). Pre-brushing and post-brushing plaque scores were recorded at baseline, 3 months, 6 months, 9 months (Ramjford surfaces) and 12 months for groups 1, 2, and 3 and at baseline, 3 months and 6 months for group 4. Pre-brushing minus post-brushing plaque scores (decrements) were significantly higher in the PBR group at baseline, and 6, 9, and 12 months. Using a single criterion (gingival bleeding index) there were no differences between the 4 groups at any of the 5 assessments, hence, the clinical significance of the higher plaque removal scores in the PBR group remains in doubt.

The relationship of candidiasis to linear gingival erythema in HIV-infected homosexual men and parenteral drug users.

Periodontal status was evaluated in two cohorts participating in a study of the natural history of human immunodeficiency virus (HIV) infection. One cohort consisted of 77 seropositive and 44 seronegative homosexual men, and the other cohort was comprised of 44 seropositive and 39 seronegative parenteral drug users (PDU). No differences were observed between seropositive and seronegative individuals within a cohort in terms of clinical periodontal parameters (percent of sites with > or = 4 mm probing depth, percent of sites exhibiting bleeding on probing, mean oral hygiene index). The PDU displayed more existing periodontal disease than the homosexual men. Periodontal disease in the seropositive individuals in both cohorts was not strictly related to the number of CD4+ lymphocytes. Linear gingival erythema (LGE), defined as an erythematous band of at least 2 mm extending between adjacent papilla, was observed in all 4 groups. Seropositive homosexual men displayed more LGE than seronegative homosexual men (16.6% vs. 11.4%) and seronegative PDU displayed more LGE than seropositive PDU (38.5% vs. 29.5%), but neither difference was significant. LGE tended to be related to reduced numbers of CD4+ lymphocytes, but this relationship did not reach statistical significance. A statistically-significant relationship was found between the presence of intraoral candidiasis and LGE in seropositive homosexual men: 42.9% of these subjects with candidiasis had LGE, while only 12.7% of the subjects without candidiasis had LGE (P < .05). For the seropositive PDU, 35.3% of the individuals with candidiasis had LGE and 25.9% of the subjects without candidiasis displayed LGE, but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy of diagnoses of HIV-related oral lesions by medical clinicians. Findings from the Women's Interagency HIV Study.

OBJECTIVE: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions. METHODS: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities. RESULTS: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively. CONCLUSIONS: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

Oral mucositis with features of psoriasis: report of a case and review of the literature.

An unusual case of oral mucositis with features of psoriasis is reported along with a review of the cases of oral psoriasis in the literature. The case reported involved a crusted lesion on the upper lip and erythematous lesions on the labial mucosa, buccal mucosa, and denture-bearing palatal mucosa. In addition, lesions resembling geographic tongue and ectopic geographic tongue were present. All lesions exhibited multiple small pustules. The review of the literature compares the distribution and clinical appearance of previously reported cases of oral psoriasis.

Oral lesions as markers of severe immunosuppression in HIV-infected homosexual men and injection drug users.

OBJECTIVES: We examined the diagnostic utility of the presence of oral lesions, individually and in combination, in identifying severe immunosuppression, defined as CD4 cell count under 200. STUDY DESIGN: Data were collected on 82 HIV-seropositive homosexual men and 82 HIV-seropositive injection drug users who volunteered to participate in a longitudinal study of HIV infection. CD4 cell counts were measured within 24 hours of oral examination. METHODS: Sensitivity, specificity, positive predictive value, negative predictive value, and the odds ratio were computed to assess the association between oral lesions and CD4 less than 200. In addition to the individual lesions, we studied the diagnostic properties of sets of three to six lesions. For each set of lesions, a patient was classified as positive for the set if he or she had one or more lesions in that set. RESULTS: In homosexual men and injection drug users, individual lesions had low sensitivity, high specificity, and moderate positive and negative predictive values. Odds ratios reflected weak correlation to immunosuppression. When lesion sets were considered in homosexual men, sensitivity rose dramatically with only modest decreases in specificity. The positive and negative predictive values remained almost the same. Similar results for lesion sets were obtained in injection drug users, with greater reduction in specificity but stable positive and negative predictive values. Odds ratios indicated that for homosexual men, the more lesions included in the set, the stronger the correlation with immunosuppression. For injection drug users, strong correlations were observed for all lesion sets. CONCLUSIONS: Analysis of sensitivities and odds ratios in homosexual men suggest that it may be valid to note the occurrence of a greater number of oral lesions than is currently done in staging patients with HIV infection. Among injection drug users, monitoring a larger number of lesions neither improves nor reduces the correlation to severe immunosuppression.

Identifying oral lesions associated with crack cocaine use.

Dental patients who smoke crack cocaine are at higher risk for HIV infection and other medical concerns including stroke, heart failure and pulmonary hemorrhage. Four cases are reported which illustrate oral ulcers caused by crack cocaine usage.

Tuberculosis.

Dental health care providers must play an active role in preventing the transmission of tuberculosis. The information presented here should allow them to appropriately identify and refer patients who may be infectious, identify oral lesions which may be due to tuberculosis, and develop and implement an infection control plan to prevent transmission in the dental setting.

HIV infection affects Streptococcus mutans levels, but not genotypes.

We report a clinical study that examines whether HIV infection affects Streptococcus mutans colonization in the oral cavity. Whole stimulated saliva samples were collected from 46 HIV-seropositive individuals and 69 HIV-seronegative control individuals. The level of S. mutans colonization was determined by conventional culture methods. The genotype of S. mutans was compared between 10 HIV-positive individuals before and after highly active antiretroviral therapy (HAART) and 10 non-HIV-infected control individuals. The results were analyzed against viral load, CD4+ and CD8+ T-cell counts, salivary flow rate, and caries status. We observed that S. mutans levels were higher in HIV-infected individuals than in the non-HIV-infected control individuals (p = 0.013). No significant differences in S. mutans genotypes were found between the two groups over the six-month study period, even after HAART. There was a bivariate linear relationship between S. mutans levels and CD8+ counts (r = 0.412; p = 0.007), but not between S. mutans levels and either CD4+ counts or viral load. Furthermore, compared with non-HIV-infected control individuals, HIV-infected individuals experienced lower salivary secretion (p = 0.009) and a positive trend toward more decayed tooth surfaces (p = 0.027). These findings suggest that HIV infection can have a significant effect on the level of S. mutans, but not genotypes.

Oral health-related quality of life among HIV-infected and at-risk women.

OBJECTIVES: Objective measures of dental diseases reflect only their clinical end-point. There is a need to use multidimensional measures of diseases that consider their psychosocial aspects and functional impact. The aim of this study is to compare the oral health-related quality of life (OHRQOL) between a group of HIV-infected women and a similar group of at-risk HIV-uninfected women, and to investigate the role of potential confounding clinical oral health and behavioral factors. METHODS: Our sample included HIV-infected women (87%) and women at risk for HIV infection (13%) followed up for 5.5 years. OHRQOL was measured using the short version of the Oral Health Impact Profile (OHIP-14), which is a validated and reliable instrument. RESULTS: HIV-infected women averaged 10% poorer OHRQOL than HIV-uninfected women; this difference was not apparent after adjusting for the number of study visits attended and significant behavioral and clinical oral health factors. The OHRQOL was inversely related to dental and periodontal diseases and to smoking and freebase cocaine use; these relationships were not confounded by HIV status. CONCLUSIONS: The study identified specific clinical and behavioral factors where dental professionals can intervene to possibly improve the OHRQOL of HIV-infected or at-risk HIV-uninfected women.

Dental lesions: diagnosis and treatment.

Oral health care has been an integral part of the care of patients with HIV infection and AIDS since the disease was first identified in the early eighties. The spectrum of HIV-associated opportunistic diseases occurring in the oral cavity propelled dental health care providers to the forefront of patient care. Infection control issues soon became important in oral health care for patients infected with HIV, and for the first decade these two issues overshadowed the concerns about appropriate management of the dental needs of HIV-infected patients. Several concerns need to be considered in the management of dental care for patients infected with HIV. These include decreased salivary flow and increased sugar intake, prevention and management of routine inflammatory gingival and periodontal disease as well as the atypical forms of gingival and periodontal disease associated with HIV infection (linear gingival erythema [LGE], necrotizing ulcerative gingivitis [NUG] and necrotizing ulcerative periodontitis [NUP]). Finally, although reports of complications secondary to dental treatment of HIV-infected individuals are rare, it is important to consider those factors related to the medical status of HIV-infected patients which may interfere with oral health care. These include potential bleeding problems related to thrombocytopenia and disease or medication related liver abnormalities, increased risk of local infection particularly in patients with severe neutropenia and adverse effects of multiple medications taken by HIV patients. Prevention and management of dental and periodontal disease in HIV-infected individuals is important to self esteem, quality of life and maintenance of adequate nutritional intake. Oral health care continues to be an important component of overall health care for HIV-infected patients.

A prevalence study of denture stomatitis in subjects with diabetes mellitus or elevated plasma glucose levels.

The purpose of this study was to determine if a relation between diabetes mellitus and denture stomatitis could be supported by observing an increased prevalence of denture stomatitis in subjects with either diagnosed diabetes mellitus or elevated plasma glucose levels. The study involved 301 subjects wearing either complete or partial maxillary dentures. Medical history information, oral examination records, and laboratory data were used for the study. No significant increase in the prevalence of denture stomatitis was found in those subjects with either previously diagnosed diabetes mellitus or elevated plasma glucose levels when compared with subjects with normal glucose metabolism.