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.

Effect of highly active antiretroviral therapy on frequency of oral warts.

To investigate changes in the pattern of oral disease associated with highly active antiretroviral therapy (HAART), we assessed the frequency of these lesions in our clinic over 9 years. We retrospectively studied 1280 patients seen between July, 1990, and June, 1999, and related oral findings to medication use, immune function, and viral load. We found significant decreases in oral candidosis, hairy leucoplakia, and Kaposi's sarcoma over time, but no change in the occurrence of aphthous ulcers. There was an increase in salivary-gland disease and a striking increase in warts: three-fold for patients on antiretroviral therapy and six-fold for those on HAART (p=0.01). This pattern of oral disease in a referral clinic suggests that an increase in oral warts could be occurring as a complication of HAART.

Oral manifestations and dental status in paediatric HIV infection.

OBJECTIVE: To describe the incidence and prevalence of oral manifestations of HIV infection in a population of perinatally infected children. DESIGN: Retrospective and prospective study of a cohort of perinatally HIV-infected children. SETTING: Community hospital and community-based paediatric clinic. SAMPLE AND METHODS: Forty perinatally HIV-infected children with a median age of 12 months were eligible and selected for the study, which included a medical chart review from birth and prospective follow-up. Each child was examined quarterly for oral manifestations, tooth eruption, and for 27 children, caries and periodontal status. RESULTS: The incidence of pseudomembranous candidiasis was 43% (95% CI, 27-58%) within 6 months of birth. Oral candidiasis (defined as pseudomembranous or erythematous) was positively associated with low CD4 counts and the occurrence of plaque. Children with low CD4 counts were also found to have fewer teeth than children with high CD4 counts, after adjusting for age. CONCLUSIONS: Oral manifestations are common in paediatric HIV infection and are possible predictors of HIV disease progression. Primary care of HIV-infected children should include periodic oral examinations to monitor their HIV disease progression and to alleviate symptoms associated with oral opportunistic infections.

Association of cutaneous and oral diseases in HIV-infected men.

OBJECTIVES: Mucocutaneous diseases are common in patients infected with human immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV-infected people are at high risk, we sought those that are strongly associated with specific HIV-related oral lesions and with progression of HIV disease. DESIGN: A cross-sectional study of HIV-positive outpatients referred to a university stomatology clinic for diagnosis and treatment of oral diseases. Each subject underwent both complete oral and cutaneous examinations. RESULTS: Among 55 men, with a median age of 41 years and a median CD4 cell count of 125/microliter (range 0-950/microliter), 93% had active oral diseases or conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma (KS), and xerostomia, and 95% had skin conditions, including onychomycosis, dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum were associated with oral HIV-sentinel lesions (oral candidiasis, hairy leukoplakia, and KS), with low CD4 cell counts, and with AIDS. CONCLUSION: Our results suggest that xerosis and seborrheic dermatitis may be early harbingers of HIV disease progression. Their roles as predictors warrant further study, based on their associations with low CD4 cell counts and AIDS and strong co-prevalence with one of the most common HIV-related oral lesions, oral candidiasis.

Effect of cigarette smoking on HIV-related oral lesions.

To determine whether the presence of specific oral lesions is associated with cigarette smoking among HIV-infected patients, we analyzed cross-sectional data (CD4 cell count, smoking history, and oral examination findings) from 1,058 HIV-infected male patients who received clinical care at the University of California, San Francisco. Oral AIDS Center Clinic. To control for potential confounding by the level of immune suppression, final analyses were limited to participants (n = 693) on whom CD4 cell count data (within 180 days of study visit) were available. Six percent of subjects had normal examination findings, 16% had nonnormal findings (but none of the six lesions of interest), 47% had lesions of a single type, and 31% had a combination of two or more types of lesions. After adjusting for CD4 cell count, current smokers were significantly more likely to have candidiasis (odds ratio [OR] = 1.84; 95% confidence interval [CI] 1.34-2.54) and warts (OR = 2.09; 95% CI 1.15-3.81) and less likely to have aphthous ulcers (OR = 0.24; 95% CI 0.14-0.42) than were current nonsmokers. These results suggest a strong association between cigarette smoking and the presence of specific HIV-related oral lesions.

Development of oral lesions in human immunodeficiency virus-infected transfusion recipients and hemophiliacs.

The authors used multivariate repeated-measures transition models to identify risk factors for two oral lesions related to human immunodeficiency virus (HIV)-candidiasis and hairy leukoplakia-in 152 HIV-infected blood transfusion recipients and hemophiliacs. Subjects were examined for occurrences of these lesions every 6 months from July 1985 through March 1993, yielding 1,076 study visits. It was found that, after adjustment for the CD4:CD8 T-lymphocyte ratio, patients with a history of candidiasis in the previous 18 months were at high risk of lesion recurrence. This risk increased with the number of prior episodes and with the recency of the episode(s). A history of hairy leukoplakia was less predictive of persistence of that lesion after adjustment for significant risk factors (including candidiasis and use of antifungal agents at the current examination, a low CD4:CD8 cell ratio, and age less than 40 years). The authors also found a high coprevalence of candidiasis and hairy leukoplakia in these subjects. These results suggest that HIV-infected patients with oral candidiasis should be carefully monitored for subsequent episodes over the next 12-18 months, and patients with either oral candidiasis or hairy leukoplakia and a low CD4:CD8 cell ratio should be carefully examined for the other type of lesion as well.

T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia.

The incidence of human papillomavirus (HPV)-related cervical intraepithelial neoplasia (CIN) and cervical cancer is increased with immunodeficiency, but the role of immune response, including cell-mediated immunity, in disease prevention is not well understood. In this study, T-cell proliferative responses to six synthetic peptides with predicted immunogenic determinants from the HPV-16 E4, E6, E7, and L1 open reading frames were analyzed in 22 sexually active women with new-onset CIN and 65 sexually active women without cervical disease, characterized by cytology, colposcopy, and HPV testing. T-cell proliferative responses were demonstrated to all six HPV-16 peptides. Although not statistically significant, rates of reactivity to E6 (24-45) were higher among sexually active women without disease (26%) than among women with current CIN (7%), as was the overall number of peptides stimulating a response. Women with CIN may not respond to selected HPV antigens as well as women without disease do.

Risk factors for HIV-related orofacial soft-tissue manifestations in children.

A retrospective review of the medical records of 492 children perinatally exposed to the human immunodeficiency virus (HIV) compared the prevalence of orofacial soft-tissue manifestations in HIV-infected and noninfected children, identified risk factors for occurrence of orofacial lesions in HIV-infected children, and investigated specific orofacial lesions as indicators of progression of HIV disease. Application of eligibility criteria and the Centers for Disease Control classification of pediatric HIV infection resulted in selection of a study group of 91 HIV-positive children and a control group of 185 HIV-seronegative children who had seroreverted. Analysis of oral lesions showed that 67% of the study group and 8% of the control group had oropharyngeal candidiasis (OPC), 4% of the study group and 0% of the control group had parotid enlargement, and 3% of the study group and 0% of the control group had herpes simplex; all three differences were significant at P < 0.04. No statistically significant association was found between OPC and the risk factors of gender, ethnicity, or mode of delivery (vaginal versus cesarean). However, OPC was associated significantly with all progression markers examined: failure to thrive, use of antiretroviral agents, lower CD4 counts, and development of acquired immunodeficiency syndrome (AIDS). Orofacial manifestations are common in pediatric HIV infection and may serve as markers of infection and predictors of progression of HIV disease to AIDS.

Time from HIV seroconversion to oral candidiasis or hairy leukoplakia among homosexual and bisexual men enrolled in three prospective cohorts.

OBJECTIVES: We evaluated time from HIV seroconversion to diagnosis of two common oral lesions associated with HIV infection and disease progression. DESIGN: Oral examinations were performed on homosexual and bisexual men enrolled in prospective cohorts. SETTING: Homosexual and bisexual men were followed in three epidemiologic cohort studies in San Francisco, California, USA. PARTICIPANTS: Data were evaluated from 80 men with well-defined dates of HIV seroconversion from 1984 through 1991. MAIN OUTCOME MEASURES: We determined the cumulative incidence of oral candidiasis and hairy leukoplakia after HIV seroconversion. RESULTS: Four per cent of men developed oral candidiasis within 1 year after HIV seroconversion, 8% within 2, 15% within 3, 18% within 4, and 26% within 5 years. Nine per cent developed hairy leukoplakia within 1 year, 16% within 2, 25% within 3, 35% within 4, and 42% within 5 years. The median CD4+ count was 391 x 10(6)/l when oral candidiasis was first reported and 468 x 10(6)/l when hairy leukoplakia was first reported. CONCLUSIONS: Oral candidiasis or hairy leukoplakia appeared in a significant proportion of HIV-infected homosexual and bisexual men. These lesions occurred relatively soon after HIV seroconversion, typically before AIDS. Evaluation of HIV-infected individuals for these lesions has many potential clinical and research benefits, including the possible use of oral lesions as primary end-points in clinical trials.