Candidiasis In HIV-infected Patients Research Articles

<i>CDR1, CDR2, MDR1</i> and <i>ERG11</i> expression in azole resistant <i>Сandida albicans</i> isolated from HIV-infected patients in city of Moscow

Candida fungi are common opportunistic microorganisms capable of causing infections of various localization, as well as life-threatening conditions in immunocompromised patients, such as HIV-infected individuals, oncology patients, subjects undergoing HSCT, which number has been steadily increasing in recent years. In addition, resistance to anti-fungal drugs has been spreading as well. Naturally sensitive to azoles, C. albicans possess a variety of mechanisms of acquired resistance, including efflux transporters and target protein-encoding gene amplification. This study was conducted to assess a prevalence of such mechanisms in the isolates sample obtained from HIV-infected patients in the Moscow region of the Russian Federation, characterize a relationship between these mechanisms and patterns of developing drug resistance. 18 strains of C. albicans resistant to fluconazole and voriconazole were isolated from HIV-infected patients with recurrent oropharyngeal candidiasis in the Moscow region. The expression levels of the ERG11, MDR1, CDR1, CDR2 genes involved in the formation of acquired azole resistance were measured using quantitative PCR, the 2CT method with ACT and PMA genes as control genes and reference values of sensitive isolates. Expression levels exceeding the average values of sensitive isolates by more than 3 standard deviations were considered significantly elevated. In most of the isolates, elevated levels of CDR1 and CDR2 gene expression were found: 89% and 78%, respectively. The expression level of the MDR1 gene was increased only in 28% of cases. ERG11 expression levels were significantly elevated in 78% of the isolates. Expression levels of all resistance genes studied were significantly increased in 4 strains. In this sample of C. albicans isolates, acquired resistance is mainly associated with efflux vectors encoded by the CDR1 and CDR2 genes. Also, in most isolates, an increased expression level for the azole target protein gene ERG11 was detected. The expression level of the efflux transporter gene MDR1 was increased in the smallest number of samples. It is also impossible to exclude a potential role of other mechanisms in developing acquired resistance, such as mutations in the ERG11 gene. It can be assumed that the identified mechanisms of resistance result from long-term, widespread, and sometimes uncontrolled use of azoles, including those in treatment and prevention of candidiasis in HIV-infected patients.

P350 Oropharyngeal candidiasis in HIV infected patients: associated risk factors and antifungal susceptibility testing of candida species by disc diffusion method

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesTo isolate and identify Candida species by the standard microbiological method.To estimate the frequency of oral Candidiasis according to age, sex, and other factors [CD4 + count, ART, tobacco consumption, diabetes, upper respiratory tract infection (URTI), recent antibiotic consumption] in HIV-positive patients.To determine the Antifungal Susceptibility pattern of the Candida species by Disc Diffusion Method.MethodologyA hospital-based cross-sectional study was conducted for 6 months in the Department of Microbiology of Sukraraj Tropical and Infectious Disease Hospital, Kathmandu, Teku, Nepal. A total of 408 HIV-positive patients attending the ART center of the hospital of different age and sex were included in the study. Study variables like CD4 + count, tobacco consumption, diabetes, URTI, and recent antibiotic consumption were noted.Standard microbiological guidelines were followed for the oral swab collection and transportation. Specimen was seeded on SDA agar plates (SDA with chloramphenicol and cycloheximide). Preliminary identification of the Candida was done on the basis of colony characteristics, gram staining, and germ tube test. Further for the speciation of Candida species, HiCrome™ Candida Differential Agar (HImedia, India) was applied where on the basis of coloration and colony morphology speciation was done. Similarly, Cornmeal Agar (Dalmau plate culture technique) and sugar Fermentation test were applied to confirm the Candida species.Muller-Hinton agar supplemented with 2% glucose and 0.5 μg/ml methylene blue dye (GMB) medium was used to perform the antifungal susceptibility testing of Candida isolates. Antifungal susceptibility testing (AST) of isolates was performed and interpreted according to Clinical and Laboratory Standards Institute (CLSI) M44-A document. Candida albicans ATCC 90028 was taken as the reference strain. All the data were entered in Microsoft excel and Chi-square was used to find out the association between the frequency of oral candidiasis and study variables.ResultsAmong 408 studied subjects, 225 (55.1%) were males and 183 (44.9%) were females. Of the participants, 116 (28.4%) had regular tobacco smoking habit, diabetes 10 (2.5%), URTIs 30 (7.4%), antibiotic consumption 44 (10.8%) and ART use 394 (96.6%). The CD4 + cell count of respondents ranged from 12 - 2425 cells/mm³. Candida albicans 53 (81.5%) was the most frequently encountered species followed by C. tropicalis 3 (4.6%), C. krusei 2 (3.1%), C. glabrata 1 (1.5%) and 6 (9.2%) other Candida species. A total of 26 patients had CD4+ ≤200 cells/mm3 and 39 patients had CD4+ >200 cells/mm3. There was no significant association in the occurrence of oral candidiasis among males and females (P = .966), tobacco consumption (P = .051), ART use (P = .188), diabetes (P = .722). Whereas, there was a significant association between oral Candida carriage and CD4 + cell count ≤ 200 cells/mm3 (P <.001), URTI (P = .029), and recent antibiotic consumption (P = .002). Amphotericin B was the most potent antifungal followed by voriconazole, itraconazole, and conversely fluconazole the most resistant.Conclusion Candida albicans was the common species isolated in our study. Candida Chrome Agar can be used as a routine media for rapid identification and Candida speciation. AST needs to be done routinely to know the susceptibility pattern of isolates and initiate proper treatment of patients. Since oral yeast colonization was associated with low CD4 + count (<200 cells/mm3). Thus, oral lesions can serve as early markers for HIV infection.

Epidemiology and Prevalence of Oral Candidiasis in HIV Patients From Chad in the Post-HAART Era.

Oral candidiasis remains a common problem in HIV-infected individuals, especially in sub-Saharan Africa. Here, we performed the first study in Chad on the prevalence of oral yeasts carriage and oral candidiasis in HIV-positive subjects from southern Chad and analyzed the influence of HAART, CD4+ T-cell numbers, and antimycotics in 589 patients. These patients were recruited from a specialized medical center for HIV patients in Sarh and from a rural medical health dispensary in the vicinity, including a total of 384 HIV-positive and 205 HIV-negative individuals. Yeasts obtained from oral specimen were identified by MALDI-TOF MS and their antifungal susceptibility profiles determined. The overall prevalence of yeast colonization and symptomatic oral candidiasis in HIV-infected patients was 25.1%. The prevalence of oral candidiasis was higher in untreated than in HAART-treated HIV-positive patients (16% vs. 2%; p < 0.01). Oral candidiasis was furthermore associated with high fungal burdens of Candida albicans and a CD4+ T-cell number <200/μl. A shift toward non-albicans Candida species was observed under nucleoside-based HAART therapy. Azole antifungal drug resistance was only observed for the intrinsically resistant species Candida krusei and Candida glabrata. Prevalence of oral candidiasis in the studied area was very low. The species distribution was similar to other countries around the world, with C. albicans being dominant. Candida dubliniensis was not isolated. Nucleoside-based HAART therapy significantly reduced oral colonization as well as occurrence of oral candidiasis caused by C. albicans and led to a species shift toward non-albicans species. Antifungal resistance was not yet a concern in Chad.

RESEARCH ANTIFUNGAL THERAPY OF OROPHARYNGEAL CANDIDIASIS IN HIV-INFECTED PATIENTS

Modern medicine has made significant advances in the treatment of fungal infections. The problem of drug resistance of such a common conditional pathogen as Candida remains relevant for the last decade. The aims of the study were: 1) analysis of species and strain drift of Candida in patients with HIV/AIDS from oropharynx and intestine in two years; 2) the analysis of the dynamics of the sensitivity of Candida to standard antimycotic drugs. Treatment of candidiasis in HIV-infected patients leads to changes in the species and strain composition of Candida. After eradication of C. albicans which is sensitive to fluconazole, more resistant strains of other species (glabratae, krusei. tropicalis) takes its place in the biotope, which is one of the reasons for the low effectiveness of antimycotic therapy.

RESEARCH ANTIFUNGAL THERAPY OF OROPHARYNGEAL CANDIDIASIS IN HIV-INFECTED PATIENTS

Modern medicine has made significant advances in the treatment of fungal infections. The problem of drug resistance of such a common conditional pathogen as Candida remains relevant for the last decade. The aims of the study were: 1) analysis of species and strain drift of Candida in patients with HIV/AIDS from oropharynx and intestine in two years; 2) the analysis of the dynamics of the sensitivity of Candida to standard antimycotic drugs. Treatment of candidiasis in HIV-infected patients leads to changes in the species and strain composition of Candida. After eradication of C. albicans which is sensitive to fluconazole, more resistant strains of other species (glabratae, krusei. tropicalis) takes its place in the biotope, which is one of the reasons for the low effectiveness of antimycotic therapy.

Incidência de Candida spp. na mucosa oral de pacientes infectados pelo vírus da imunodeficiência humana (HIV) no município de Santo Ângelo -RS

Justificativa: Atualmente há um aumento das infecções fúngicas, especialmente em pacientes imunocomprometidos. Dentre os fungos causadores de infecções invasivas destacam-se as leveduras do gênero Candida, considerada marcador de progressão do HIV. A terapêutica antifúngica e diagnóstico são importantes para o tratamento de candidíase oral, devido à resistência atribuída a algumas espécies. Assim, destaca-se a importância de determinar a incidência de candidíase oral em pacientes portadores do vírus do HIV. Objetivo: Pesquisar a incidência de Candida spp em pacientes HIV positivos, as espécies, os fatores de virulência e a sensibilidade ao fluconazol. Metodologia: pesquisou-se a colonização da mucosa oral de pacientes HIV positivos com o auxílio de swab estéril e o cultivo em ágar Sabouraud Dextrose. Estudou-se a atividade de proteinase e fosfolipase. O teste de suscetibilidade foi realizado pelo método de disco difusão. Preencheu-se uma ficha com dados sócio-econômicos, clínicos e informações quanto as medicações e sintomatologias dos pacientes. Resultados: A amostra constituiu-se de 45 pessoas. A média de idade dos pacientes foi de 38 anos (±13,63). A taxa de colonização oral por Candida em pacientes HIV foi de 53,3%, destes, 95,83% pertencentes à espécie albicans. Os isolados apresentaram atividade positiva e fortemente positiva para fosfolipase e proteinase. No teste de suscetibilidade 25% dos isolados mostraram-se resistentes ao fluconazol. Conclusão: O diagnóstico precoce da candidíase em pacientes infectados pelo HIV é fundamental tanto para o tratamento imediato, quanto para melhorar a sua qualidade de vida, uma vez que a candidíase é uma lesão bucal muito frequente nesta população.

Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection.

Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.

THE CLINICAL COURSE OF INVASIVE CANDIDIASIS IN HIV-INFECTED PATIENTS

The article presents the results of observation of 21 patients with invasive candidiasis, developed on the background of HIV infection for the period 2007-2013. The features of clinical course of the disease and the risk factors for its occurrence are described. The clinical ркЫп of invasive candidiasis in HIV-infected patients is similar to the clinical picturde seen in bacterial sepsis, it is characterized by the severe course and the high fatality. The risk factors are the pronounced immune deficiency, the absence of antiretroviral ^тру and the presence of 2 or more foci of the s^etAnal candidiasis. The diagnosis of the hematogenous dissemination should be carried out in all HIV-infected patients with the reference symptoms.

Candida and candidiasis in HIV-infected patients

In this era of efficacious antiretroviral therapy and consequent immune reconstitution, oropharyngeal and esophageal candidiasis (OPC and OEC) still remain two clinically relevant presentations in the global HIV setting. Both diseases are predominantly caused by Candida albicans, a polymorphic fungus which is a commensal microbe in the healthy individual but can become an aggressive pathogen in a debilitated host. Actually, C. albicans commensalism is not the result of a benign behavior of one of the many components of human microbiota, but rather the result of host's potent innate and adaptive immune responses that restrict the growth of a potentially dangerous microrganism on the epithelia. An important asset guarding against the fungus is the Th17 functional subset of T helper cells. The selective loss of these cells with the progression of HIV infection causes the decay of fungal containment on the oral epithelium and allows C. albicans to express its pathogenic potential. An important part of this potential is represented by mechanisms to evade host immunity and enhance inflammation and immunoactivation. In C. albicans, these mechanisms are mostly incorporated into and expressed by characteristic morphogenic transitions such as the yeast-to-hyphal growth and the white-to-opaque switch. In addition, HIV infection generates an 'environment' selecting for overexpression of the virulence potential by the fungus, particularly concerning the secreted aspartyl proteinases (Saps). These enzymes can degrade critical host defense components such as complement and epithelial defensive proteins such as histatin-5 and E-cadherin. It appears that part of this enhanced Candida virulence could be induced by the binding of the fungus to HIV and/or induced by HIV proteins such as GP160 and tat. Both OPC and OEC can be controlled by old and new antimycotics, but in the absence of host collaboration, anticandidal therapy may become ineffective in the long run. For these reasons, new therapeutics targeting virulence factors and specific immune interventions are being addressed. Among these new approaches, vaccination is a promising one. Two subunit vaccines based on antigens dominantly expressed by C. albicans in vivo, that is the Als3 adhesin and Sap2, have recently undergone phase 1 clinical trials. Overall, studies of Candida and candidiasis in the HIV-positive patient while certainly contributing to a more effective control of the microorganism may also provide useful information on HIV-host relationship itself that can assist the fight against the virus.

Antimicrobial Photodynamic Therapy in the Treatment of Oral Candidiasis in HIV-Infected Patients

Antimicrobial photodynamic therapy (aPDT) has been used to combat local infections, and it consists of the combination of a photosensitizer, a light source, and reactive oxygen species (ROS) to kill microbial cells. In this study, we evaluated the effectiveness of aPDT in the treatment of candidiasis in HIV-infected patients. Twenty-one patients were divided into three groups. Control group (CG) was treated with the conventional medication for candidiasis (fluconazole 100 mg/day during 14 days). Laser group (LG) was subjected to low-level laser therapy (LLLT), wavelength 660 nm, power of 30 mW, and fluence of 7.5 J/cm(2), in contact with mucosa during 10 sec on the affected point. An aPDT group (aPDTG) was treated with aPDT, that is, combination of a low-power laser and methylene blue 450 μg/mL. Pre-irradiation time was 1 min. Parameters of irradiation were the same ones as for the LG, and patients were single irradiated. Patients were clinically evaluated and culture analysis was performed before, immediately after, and 7, 15, and 30 days after the treatment. Our results showed that fluconazole was effective; however, it did not prevent the return of the candidiasis in short-term. LLLT per se did not show any reduction on Candida spp. aPDT eradicated 100% of the colonies of this fungus and the patients did not show recurrence of candidiasis up to 30 days after the irradiation. These findings suggest that aPDT is a potential approach to oral candidiasis treatment in HIV-infected patients.

Candida species isolated from the vaginal mucosa of HIV-infected women in Salvador, Bahia, Brazil

BackgroundVulvovaginal candidiasis (VVC) is the second most common vaginal infection. HIV-infection is a risk factor for this infection. ObjectiveTo determine the frequency of VVC and to describe the main Candida species isolated and their susceptibility to antifungal drugs in HIV-infected patients, compared to HIV-uninfected women in Salvador, Brazil. MethodsCross-sectional study including a group of 64 HIV-infected women and 76 uninfected women, followed up at the AIDS reference center and at the Gynecological Clinic of Escola Bahiana de Medicina e Saúde Pública (Salvador, Bahia, Brazil). ResultsFrequency of Candida spp. was higher in HIV-infected women (29.7%) than in HIV-uninfected controls (14.5%) (p=0.02). The odds ratio value for vulvovaginal candidiasis in HIV-infected patients was 2.6 (95% CI: 1.07 − 6.32 p=0.03). Candida albicans was the most commonly isolated species in both HIV-infected (52.3%) and uninfected women (85.7%), followed by C. parapsolis in 17.6% and 14.3%, respectively. In HIV-infected women, C. glabrata, C. parapsilosis, and a coinfection of C. albicans and C. glabrata were also identified. There was no significant difference between Candida species isolated from the vaginal mucosa of women with VVC and colonization of the vaginal mucosa of HIV-infected and HIV-uninfected women. One C. glabrata isolate from an HIV-infected patient was resistant to fluconazole and other two isolates exhibited a dose-dependent susceptibility. ConclusionOur results confirm a higher frequency of Candida spp. isolated from the vaginal mucosa of HIV-infected women and a broader spectrum of species involved. Only Candida glabrata isolates showed decreased susceptibility to fluconazole.

Identification of gentian violet concentration that does not stain oral mucosa, possesses anti-candidal activity and is well tolerated

Gentian violet (GV) is recommended for initial treatment of oral candidiasis in HIV-infected patients in resource-limited settings. Currently GV is not used because of its staining effects. In this study, we investigated the staining capacity of three different concentrations of GV to determine a concentration that does not cause staining. The selected concentration that did not cause staining was evaluated for its physical stability and antifungal activity. Fifteen healthy participants were randomized to rinse twice daily for 14 days with one of three GV concentrations: 0.1%, 0.0085%, or 0.00165%. Oral examination and intra-oral photographs were performed at baseline and at the end of therapy. Participants responded to a questionnaire to assess adverse events. Antifungal activity was evaluated using the Clinical and Laboratory Standard Institute methodology. GV at a concentration of 0.00165% did not stain the oral mucosa and was well tolerated. GV at a concentration of 0.00165% was stable and possessed antifungal activity when stored at certain temperatures for different time periods. Gentian violet solution at the concentration of 0.00165% does not stain the oral mucosa, is stable and possesses potent antifungal activity.

T cells specific for Candida albicans antigens and producing type 2 cytokines in lesional mucosa of untreated HIV-infected patients with pseudomembranous oropharyngeal candidiasis

Factors influencing the susceptibility to mucosal candidiasis in HIV-infected patients are not clearly understood. Since in animal models of candidiasis the T helper (Th)1- or Th2-responses are protective or non-protective, respectively, this study was aimed to evaluate the cytokine profile of T-cell response to Candida albicans in the blood and lesional tissues of human immunodeficiency virus (HIV)-infected individuals, suffering, or not, from pseudomembranous oropharyngeal candidiasis (POPC), of HIV-negative women suffering from recurrent vaginal candidiasis (RVC) and of healthy controls. Peripheral blood mononuclear cells from HIV-infected and RVC patients proliferated to C. albicans antigen more than controls. Upon antigen activation, T cells from HIV-infected patients produced low interferon (IFN)-γ, while only T cells from patients with POPC displayed high interleukin (IL)-4 and IL-5 production. POPC-positive patients also showed higher serum IgE levels than POPC-negative patients. T-cell clones generated from the oral mucosa of one HIV-infected patient with POPC produced IL-4, but not IFN-γ (Th2 phenotype), whereas clones obtained from vaginal mucosa from one RVC patient or one healthy donor showed a Th1 profile. These findings, showing a non-protective Th0/Th2 response to C. albicans antigen in the blood and lesional mucosa of HIV-infected patients with POPC, may explain the high susceptibility of candidiasis in these subjects.

Assessment of the Association Between HIV Viral Load and CD4 Cell Count on the Occurrence of Oropharyngeal Candidiasis in HIV-Infected Patients

Oropharyngeal candidiasis (OPC) is the most frequently observed oral infection in HIV-infected individuals. Historically, lower CD4 counts have been associated with an increased prevalence of OPC in HIV-infected patients, but HIV viral load has also recently been recognized as a possible predictive factor. We examined the impact of viral load and blood CD4 cell count on the occurrence of OPC using modern exploratory statistical analyses. The exploratory and inferential methods of classification and regression trees (CARTs) and logistic regression were used to compare the impact of viral load and CD4 cell counts on OPC status in 161 HIV-infected individuals from an outpatient clinic population in New Orleans. The use of stepwise logistic regression and CART to classify individual OPC status both identified viral load as the most important covariate, followed by CD4 cells counts. Age, sex, and highly active antiretroviral therapy use were also found to be associated with OPC status. These data strongly suggest that low viral load distinguishes those not at risk for OPC with high viral load, which also includes a heterogeneous set of predictors for OPC status, has the highest impact on OPC classification.

Oral candidiasis in HIV-infected patients and its relation to CD4 + counts: an adjunct clinical marker of HIV disease progression

Oral candidiasis in HIV-infected patients and its relation to CD4 + counts: an adjunct clinical marker of HIV disease progression

Colonization of Human Immunodeficiency Virus-Infected Outpatients in Taiwan with Candida Species

To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients in Taiwan, we have conducted a prospective cohort study of Candida colonization and its risk factors at the National Taiwan University Hospital from 1999 to 2002. More than 50% of the patients were colonized with Candida species, and 12% developed symptomatic candidiasis. Patients colonized with fluconazole-resistant strains of Candida species had a higher prevalence of candidiasis than those colonized with susceptible strains. Our analysis found that antibiotic treatment and lower CD4(+) counts (<200 cells/mm(3)) increased the rate of oropharyngeal candidiasis in HIV-infected patients, while antiretroviral therapy protected patients from the development of candidiasis.

Micafungin.

To review the pharmacology, mycology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of micafungin, an echinocandin antifungal agent. A MEDLINE search, restricted to English language, was conducted from 1978 to November 2003. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2003 and information available through the manufacturer's Web site. In vitro and preclinical studies, as well as Phase II and III clinical trials, were evaluated to summarize the clinical efficacy and safety of micafungin. All published and unpublished trials and abstracts citing micafungin were selected. Micafungin has shown in vitro activity against many yeasts and a variety of molds. Micafungin can be administered only parenterally. Efficacy has been illustrated in open noncomparative studies of esophageal candidiasis in HIV-infected patients and in comparative trials as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Adverse events appear mild and limited; the most commonly reported adverse events include hyperbilirubinemia, nausea, and diarrhea. Micafungin has activity against Aspergillus spp. and a variety of Candida spp., including azole-resistant strains. Micafungin demonstrates efficacy in the treatment of esophageal candidiasis in HIV-infected patients and appears superior to fluconazole as antifungal prophylaxis in patients undergoing hematopoietic stem-cell transplantation. Based on case reports and in vitro efficacy, micafungin may prove to be a clinically useful agent in the treatment of other fungal diseases; however, these indications await the results of clinical trials.

Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection.

Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4(+) cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8(+) T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal.

Oropharyngeal candidiasis in HIV-infected patients under treatment with protease inhibitors.

Oropharyngeal candidiasis decreased when protease inhibitors were included with other antiretrovirals to treat HIV infection. We tested oral yeast isolates of Brazilian HIV-infected individuals receiving antiretroviral therapy for protease secretion and susceptibility to ritonavir and some antifungals. We collected oral samples and identified yeasts from 19 HIV-infected patients receiving highly active antiretroviral therapy (HAART) and suspected of having oral candidiasis. Ritonavir and its excipients' effects on the isolated yeasts were tested for protease secretion by Rüchel's technique. The yeasts' susceptibility to amphotericin B (AnB), fluorocitosine (5FC), fluconazole (FZL), ketoconazole (KZL), and itraconazole (IZL) was determined by E-test (AB Biodisk). Chi-squared test determined the statistical differences. Twenty-five different positive isolates were obtained. Sixty-eight percent were C. albicans. Other isolates included C. famata (16%), C. glabrata (4%), C. tropicalis (4%), T. capitatum (4%), and 1 isolate not identified. High protease secretion was observed for most of the isolates (20/25). Ritonavir only altered enzyme secretion in 6/20 of the protease-secreting isolates. All isolates were highly sensitive to both AnB and 5FC. Antifungal activity did not change when ritonavir was added to the culture media. Some isolates were highly resistant to studied antifungals (52.2% KZL, 30.4% FZL, and 26% IZL). Resistance significantly decreased when ritonavir was added to the medium with KZL and IZL (P <.5 by chi-squared). A trend to decreased resistance was also observed with FZL but the results were not statistically significant. Candida continues to be the most prevalent fungus in the oral cavity. Although oral candidal isolates secrete protease, ritonavir does not inhibit all protease-secreting oral yeast isolates. There seems to be a synergistic effect between ritonavir and oral antifungals against fungal resistance.

Oropharyngeal candidiasis in HIV-infected patients under treatment with protease inhibitors

Objective Oropharyngeal candidiasis decreased when protease inhibitors were included with other antiretrovirals to treat HIV infection. We tested oral yeast isolates of Brazilian HIV-infected individuals receiving antiretroviral therapy for protease secretion and susceptibility to ritonavir and some antifungals. Study design We collected oral samples and identified yeasts from 19 HIV-infected patients receiving highly active antiretroviral therapy (HAART) and suspected of having oral candidiasis. Ritonavir and its excipients' effects on the isolated yeasts were tested for protease secretion by Rüchel's technique. The yeasts' susceptibility to amphotericin B (AnB), fluorocitosine (5FC), fluconazole (FZL), ketoconazole (KZL), and itraconazole (IZL) was determined by E-test (AB Biodisk). Chi-squared test determined the statistical differences. Results Twenty-five different positive isolates were obtained. Sixty-eight percent were C. albicans. Other isolates included C. famata (16%), C. glabrata (4%), C. tropicalis (4%), T. capitatum (4%), and 1 isolate not identified. High protease secretion was observed for most of the isolates (20/25). Ritonavir only altered enzyme secretion in 6/20 of the protease-secreting isolates. All isolates were highly sensitive to both AnB and 5FC. Antifungal activity did not change when ritonavir was added to the culture media. Some isolates were highly resistant to studied antifungals (52.2% KZL, 30.4% FZL, and 26% IZL). Resistance significantly decreased when ritonavir was added to the medium with KZL and IZL ( P < .5 by chi-squared). A trend to decreased resistance was also observed with FZL but the results were not statistically significant. Conclusion Candida continues to be the most prevalent fungus in the oral cavity. Although oral candidal isolates secrete protease, ritonavir does not inhibit all protease-secreting oral yeast isolates. There seems to be a synergistic effect between ritonavir and oral antifungals against fungal resistance.