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1/72. Immunopathology as a result of highly active antiretroviral therapy in hiv-1-infected patients.

    OBJECTIVE: Unusual clinical inflammatory syndromes associated with underlying previously unrecognized opportunistic infections are increasingly being noted shortly after starting highly active antiretroviral therapy (HAART). This study examined the possible relationship between such unexpected disease manifestations and in vitro parameters of microbial antigen-specific immune reactivity in patients infected with hiv-1 who had a mycobacterium avium intracellulare or mycobacterium xenopi infection. DESIGN: in vitro T-cell proliferation experiments were performed after specific stimulation of a patient's peripheral blood mononuclear cells (PBMC) with M. avium and M. xenopi antigen and non-specific stimulation with phytohaemagglutinin (PHA). The results were compared with appropriate controls. patients: Five patients who presented with unusual clinical syndromes associated with M. avium or M. xenopi infection within weeks of experiencing large rises in CD4 cell counts following the initiation of antiretroviral therapy. RESULTS: In all patients except one, mycobacteria-specific lymphoproliferative responses rose significantly following HAART; this was temporally associated with elevations in CD4 cell counts and the occurrence of clinical disease. The patient with M. xenopi infection appeared to clear his infection subsequently without antimycobacterial therapy. In three of the four patients with M. avium infection, antimycobacterial treatment could be stopped without recurrence of infection. CONCLUSION: Our findings support the hypothesis that HAART may lead to clinically relevant inflammation as a result of restoration of specific immune reactivity against microbial pathogens that are subclinically present at the time treatment is initiated. Continuation of HAART may subsequently result in protective immunity and clearance of infection.
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2/72. central nervous system toxoplasmosis in acquired immunodeficiency syndrome: An emerging disease in india.

    With the incidence of patients infected with human immuno-deficiency virus (HIV) increasing in india, the central nervous system (CNS) manifestations of the disease will be seen more frequently. The CNS may be primarily afflicted by the virus or by opportunistic infections and neoplasms secondary to the immune suppression caused by the virus. In india, although mycobacterium tuberculosis has been reported to be the most common opportunistic infection, toxoplasmosis may become as common owing to the ubiquitous nature of the protozoan. Since an empirical trial of medical therapy without histopathological diagnosis is recommended, the true incidence of this condition may remain under estimated. The role of ancillary tests such as radiology and serology in the initial diagnosis of this condition remain crucial. This report highlights two patients who were diagnosed to have acquired immuno-deficiency syndrome (AIDS) only after the biopsy of the intracranial lesion was reported as toxoplasmosis. Presently all patients for elective neurosurgery are tested for HIV antigen. The management protocol to be followed in a known patient with AIDS presenting with CNS symptoms is discussed in detail. The value of ancillary tests is also reviewed.
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3/72. Perianal cytomegalovirus ulcer in an HIV infected patient: case report and review of literature.

    We report the case of a 25-year-old man with acquired immunodeficiency syndrome, presenting with perianal ulcer and diarrhea. He had positive immunocytochemical tests for Cytomegalovirus (CMV) in circulating polymorphonuclear cells (PMN). The biopsy specimen was suggestive of CMV infection, and specific immunoperoxidase for CMV antigens positively stained endothelial cells and fibroblasts. In this report we review cutaneous CMV infection in immunocompromised patients.
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4/72. Progressive outer retinal necrosis caused by herpes simplex virus type 1 in a patient with acquired immunodeficiency syndrome.

    OBJECTIVE/BACKGROUND: To identify the etiologic agent of rapidly progressive outer retinal necrosis (PORN) in a 32-year-old man with acquired immunodeficiency syndrome (AIDS), who had retinitis developed from cytomegalovirus (CMV). Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis, diagnosed clinically as PORN. death occurred after failure of multiple organs. DESIGN: Case report. methods: Both globes were taken at autopsy, fixed in formalin, and examined histopathologically and immunohistochemically to identify causative agents in the retinal lesions. MAIN OUTCOME MEASURE: immunohistochemistry. RESULTS: All layers of the retina were severely damaged and contained focal calcification. Cytomegalic inclusion bodies were found in cells in the damaged retina of the right eye. Immunohistochemical studies for herpesviruses revealed the presence of CMV antigens in the right retina at the posterior pole and herpes simplex virus type 1 (HSV-1)-specific antigen in the periphery of both retinas. No varicella-zoster virus (VZV) antigen was detected in either retina. CONCLUSIONS: PORN has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with AIDS. Although the etiologic agent has been reported to be VZV, HSV-1 can be an etiologic agent.
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5/72. Detection of the 20-kDa virulence-associated antigen of rhodococcus equi in malakoplakia-like lesion in pleural tissue obtained from an AIDS patient.

    A malakoplakia-like lesion was detected in a pleural biopsy from an AIDS patient presenting clinical and radiologic features of pneumonia. Cultures of bronchoalveolar lavage and pleural fluid evidenced rhodococcus equi as the causative agent of pleuro-pulmonary infection. Immunochemical characterization of the R. equi isolate showed the presence of a strain similar to the ATCC 33704 reference strain presenting the capsular antigen of serotype 4, and the intermediate virulence-associated antigen of 20-kDa. Histopathology of the patient's pleural biopsy showed plaques of macrophages interspersed with lymphocytes, and intracytoplasmic cocci and bacilli in macrophages, which were variably acid-fast positive. immunohistochemistry of cocci, bacilli and their degradation products resulted strongly positive when stained with a mouse monoclonal antibody (MAb) produced against the 20-kDa antigen. This finding could have important implications for the pathogenicity of R. equi for human beings, since we do not know yet all the factors involved in the formation of malakoplakia. Indeed, the results obtained in the present study, taken together with the results obtained for pigs inoculated with R. equi strains of intermediate virulence (Madarame et al. 1998), raise the possibility that most strains presenting the 20-kDa antigen may be capable of inducing malakoplakia. If this hypothesis is confirmed by immunohistochemical analysis of human pulmonary malakoplakia cases due to R. equi, the detection of this antigen may be extremely helpful in the diagnosis and treatment of such patients. This is the first report of R. equi infection in human beings that suggests a relationship between pleural malakoplakia and the virulence-associated antigen of 20-kDa.
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6/72. case reports. Disseminated cryptococcoses without cryptococcal antigen detection.

    During the last decade cryptococcoses were most frequently diagnosed in AIDS patients, where serologically high amounts of glucoronoxylomannan (GXM) were detectable. Disseminated cryptococcoses without cryptococcal antigen detection is unusual. Between August and October 1998 disseminated cryptococcoses were diagnosed in three patients consecutively although cryptococcal antigen was not detectable. Only one of the patients was HIV infected.
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7/72. Reactivation of hepatitis b virus replication accompanied by acute hepatitis in patients receiving highly active antiretroviral therapy.

    We describe 2 patients who were initially positive for antibodies to hepatitis B surface antigen and who experienced a strong and sudden increase of hepatitis b virus (HBV) replication during highly active antiretroviral therapy (HAART). We found that reactivation of HBV replication during HAART can occur independently of lamivudine resistance or withdrawal of lamivudine, and in spite of increasing CD4( ) cell counts.
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8/72. The changing face of AIDS-related opportunism: cryptococcosis in the highly active antiretroviral therapy (HAART) era. case reports and literature review.

    Only nine cases of AIDS-related cryptococcosis have been reported until now in patients receiving highly active antiretroviral therapy (HAART), all of them with abnormal clinical features. Two HIV-infected patients who experienced an atypical relapse of cryptococcosis shortly after the start of HAART and despite maintenance antifungal treatment, are described. Six different relapses of cryptococcal meningitis were observed in a 28-month period in a patient who obtained a poor immune recovery after HAART (as shown by a CD4 lymphocyte count ranging from 78 to 149 cells/microL, opposed to a baseline level of 98 cells/microL). On the other hand, a patient with favorable immunological response to HAART (as expressed by a CD4 count growing from 7 to 186 cells/microL), experienced isolated multiple indolent cryptococcal abscesses involving head, neck, the anterior thoracic wall, and regional lymph nodes, with repeatedly negative cultures, and diagnosis obtained by both histopathologic study and positive serum antigen assay. Both our case reports are representative of novel correlations between opportunistic pathogens and immune reactivity, descending from the introduction of HAART. The first episode describes an exceedingly elevated number of disease relapses despite HAART and antifungal maintenance treatment, which may descend from an incomplete immune response to antiretroviral therapy, possibly responsible for failure in obtaining eradication of yeasts, but also for lack of disease dissemination (usually leading to a lethal multivisceral involvement in the pre-HAART era). The abnormal disease course and localization of second reported patient well depicts an "immune reconstitution syndrome" probably representing a flare-up of a latent fungal infection, caused by a rapidly effective HAART. In patients treated with HAART, AIDS-related cryptococcosis cannot therefore be ruled out by the absence of neurological involvement, and by persistingly negative cultures.
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9/72. Recurrences of cytomegalovirus retinitis in a human immunodeficiency virus-infected patient, despite potent antiretroviral therapy and apparent immune reconstitution.

    We describe a 42-year-old man with human immunodeficiency virus infection who developed multiple recurrences of cytomegalovirus (CMV) retinitis despite receiving highly active antiretroviral therapy and having apparent immune reconstitution as evidenced by CD4( ) T lymphocyte counts of > 200 cells/mm(3). Laboratory investigation during one recurrence of retinitis confirmed that there was active CMV replication in the plasma and vitreous fluid. In addition, lymphoproliferative responses to CMV antigens were absent despite evidence of reactivity to candida antigen and pokeweed mitogen. The clinical significance of this case and of other recently reported cases is discussed.
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10/72. in vitro culture, ultrastructure, antigenic, and molecular characterization of encephalitozoon cuniculi isolated from urine and sputum samples from a Spanish patient with AIDS.

    In this report we describe the cultivation of two isolates of microsporidia, one from urine and the other from sputum samples from a Spanish AIDS patient. We identified them as encephalitozoon cuniculi, type strain III (the dog genotype), based on ultrastructure, antigenic characteristics, PCR, and the sequence of the ribosomal dna internal transcribed spacer region.
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