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Background: Candidia esophagitis (CE) is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART) era., Methodology Principal Findings: A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI) endoscopy were analyzed. Sexual behavior, CD4(+) count, HIV-RNA viral load (VL), history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of the 733 subjects, 62 (8.46%) were diagnosed with CE (mild, n = 33; severe, n = 29). Of them, 56.5% (35/62) had no GI symptoms, 30.6% (19/62) had CD4 + ≥200 cells/μL, and 55.3% (21/38) had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4(+) counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds). Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29) had no GI symptoms and 44.4% (8/18) had no oral candidiasis. Median CD4(+) counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04)., Conclusions: Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings.

Human Immunodeficiency Virus (HIV)-related oral lesions can be used as markers of the immune status. The present cross-sectional study was conducted to identify the oral manifestations in HIV-infected individuals and their association with reduced Cluster of Differentiation 4 (CD4) count. The study population included known HIV-positive patients. A detailed case history of 399 HIV-positive patients was obtained and general examination was carried out. Diagnosis of oral lesions was done based on presumptive criteria of EEC Clearinghouse, 1993. The CD4 count was determined in 369 patients and correlated with oral manifestations. The prevalence of oral lesions was found to be 76.70% (n = 306). Oral candidiasis (157 (39.3%)) was the most common oral lesion associated with HIV infection. Amongst various forms of oral candidiasis, erythematous candidiasis (122 (39.3%)) outnumbered the other forms. The mean CD4 count of patients with oral lesions (207 cells/mm(3)) was less than in patients without oral lesions (291 cells/mm(3)) (P = 0.002). Oral candidiasis was found to be significantly correlated to a reduced CD4 cell count below 200 cells/mm(3) (P = 0.000; Odds ratio = 3.1; 95% Confidence interval 1.9-4.9) with good sensitivity, best specificity and positive predictive value. Oral manifestations may be used as an alternative to CD4 count at field-based settings to diagnose the immune compromised status of HIV-infected individuals.

Objective: To identify prognostic factors for the clinical effectiveness of fluconazole in HIV-1-infected patients with oropharyngeal candidiasis., Design and Setting: The study was designed as a prospective, open label, non-comparative, dose escalating, single centre trial., Patients and Methods: Thirty-four HIV-1-infected patients with oropharyngeal Candida infection were treated with 50 or 100mg fluconazoleday(-1), depending on the clinical manifestation (erythematous or pseudomembranous). The dose was doubled weekly until clinical cure. The predictive value of potential prognostic factors for the duration of treatment and cumulative fluconazole dose until cure was studied: exposure to fluconazole, previous use of fluconazole, the use of antiretroviral drugs, the CD4(+) cell count, erythematous or pseudomembranous appearance, the minimum inhibitory concentration (MIC) for fluconazole of the isolated Candida strain, and xerostomia., Results: Twenty-eight patients (with 30 episodes of oropharyngeal candidiasis) were evaluated. Twenty-five episodes were cured within 1-week of treatment, the remaining five episodes were cured within 2 weeks. No predictive value for any of the studied factors on the duration of fluconazole treatment or the cumulative fluconazole dose until cure was demonstrated., Conclusion: Because of the high susceptibility to fluconazole and the positive clinical outcome, the variation in outcome measurements was too modest to establish a significant relationship between any of the investigated potentially prognostic factors and the cumulative fluconazole dose and the duration of treatment to reach cure. On the other hand it can be concluded, that fluconazole is very effective in patients with advanced HIV infection and low CD4(+) cell counts, even if they are not using antiretroviral agents.

The aims of this study were to assess types and prevalence of HIV-related oral lesions and to correlate these lesions to the main laboratory parameters such as CD4+ cell count and plasma HIV-RNA. The study population consisted of 104 consecutive HIV+ patients living in Sicily (M=67, 64.4%; F=37, 35.6%; median age=35 years). CD4+ cell count and viral load were measured within 24 h of oral examination. Data were managed and analysed by Epi-Info 6.0. HIV-related oral lesions, as classified by the EC-Clearinghouse, were diagnosed in 35.6% of patients: these were of the Strongly Associated (SA) type in 22.1%, the Less Common Associated (LCA) type in 12.5%, and the Lesions Seen in HIV Infection (LS) type in 3.8%. CD4+ cell counts <200 x 10(6)/l were significantly associated only with SA lesions (P=0.03); median values of CD4+ cell count were also significantly correlated (P=0.02). Viral load, expressed both by median values of copies/ml (P=0.0001) and log10 copies/ml (P=0.0003), was significantly associated only with SA lesions. Treatment failure was significantly correlated to SA lesions (P=0.04). Besides the confirmed correlation with CD4 depletion, the strong association with a high level of viral load could make SA oral lesions a useful tool for identifying progression of HIV infection and could be of value in monitoring antiretroviral therapy.

Oral fluids are convenient alternatives to blood sampling for evaluating significant metabolic components. Two forms of oral fluids, oral mucosal transudates (OMT) and saliva, were collected and compared for content of soluble products of immune activation. The data confirm that OMT and saliva represent distinct body fluids. The concentrations, outputs, and analyte/protein ratios of beta-2-microglobulin (beta2M), soluble tumor necrosis factor alpha receptor II (sTNFalphaRII), and neopterin were measured. Both the OMT and the saliva of most of the individuals in the control healthy populations had measurable levels of all three activation markers. When the immune system is activated, as in human immunodeficiency virus (HIV) infection, the levels of beta2M and sTNFalphaRII are increased in both OMT and saliva compared to those in a healthy control population. OMT levels correlated better with levels in serum than did saliva and appear to reflect systemic immune activation in HIV infection. Because acquisition of oral fluids is noninvasive and easily repeatable, measurement of beta2M and/or sTNFalphaRII content in OMT could be useful in the assessment of disease activity in patients with HIV infection or chronic inflammatory diseases.

The density of Candida colonization in mouthwash fluid of 59 HIV-seropositive patients and 21 controls was determined. No significant difference in colony-forming units was found. No correlation was found between the colonizing density of Candida albicans and the CD4 count among the patients. Twenty-seven of the HIV-seropositive patients were followed for almost 3 years. No difference was found between the number of Candida albicans colony-forming units at the first and second time of sampling. Vaccination with HIV IIIB GP 160 vaccine did not have any influence on the prevalence of Candida albicans.

Objective: To develop a simple clinical staging system based on CD4 count and clinical variables that predicts progression to AIDS in HIV-infected non-AIDS patients., Design: Retrospective cohort study., Setting: A primary care outpatient clinic for HIV-infected patients at a VA Medical Center., Patients: One hundred seventy-six HIV-infected non-AIDS patients seen at the Houston VA Special Medicine Clinic between January 1986 and December 1990 and followed for a mean of 22 months. Fifty-four patients (31%) progressed to AIDS during follow-up., Measurements: The medical records were reviewed, and data corresponding to the initial (baseline) clinic visit and subsequent six-month visits were extracted., Main Results: "Predictive" baseline variables (i.e., those associated with progression to AIDS) were first identified and then examined in Cox proportional hazards modeling. In the final model, CD4 category, oral thrush, and night sweats made significant independent contributions. A three-stage prognostic system was constructed by assigning points to the three variables: CD4 > 500 cells/mm3 = 0; 500 > or = CD4 > or = 200 = 1; CD4 < 200 = 2; presence of oral thrush = 1; presence of night sweats = 1. Stages were assigned as follows: stage I = 0 points, stage II = 1-2 points, and stage III = 3-4 points. The proportions of patients who progressed to AIDS were: stage I, 6/39 (15%); stage II, 31/106 (29%); and stage III, 17/31 (55%)., Conclusions: These results demonstrate that simple, clinically sensible prognostic staging systems that predict progression to AIDS can be constructed using CD4 count and clinical variables.