CMV-infection in gay men with AIDS

Detta är en avhandling från Stockholm : Karolinska Institutet, Dept of Microbiology, Tumor and Cell Biology

Sammanfattning: Background: Before the era of combination therapy (c-ART) more than 90 % of the patients with HIV-infection died of one or more opportunistic infections (OI). We and others noted early on that CMV was an important pathogen in these patients. We investigated the OIs related to causes of death in all Venhälsan patients, with these specific questions 1) All OIs and opportunistic cancers (OC)s in patients who died with CD4+ counts below 100 x 106/mL; 2) The prevalence of CMV encephalitis (CMV-E) and Korsakoff syndrome (Paper 1); 3) CMV retinitis (CMV-R) in relation to CMV-E (Paper II); 4) CMV adrenalitis (CMV-A) and its relation to CMV-R and CMV-E, including comparison of CMV assessment by PCR in blood and the Synacthen test; 5) The correlation between CMV disease and other OIs and OCs (Papers I, II and III); 6) The interaction between CMV, Epstein Barr virus (EBV) and other human herpes viruses in a case of anaplastic large cell lymphoma (ALCL) (Paper IV) Material end methods: We followed all patients that died at Venhälsan from 1989-1996, with intensive blood testing, biopsies, culturing, X-ray, computer tomography CT, magnetic resonance imaging MRI as well as autopsy when permission was provided. We focused especially on Synacthen tests to diagnose CMV-A, neurological examinations to diagnose CMV-E and Korsakoff, and ophthalmologic examinations to diagnose CMV-R. In a case of anaplastic large cell lymphoma, we did extensive analysis of all human herpes viruses in the course of the disease. Results: Of all 219 patients, that died with CD4+ < 100 x 106/mL 87% showed signs of reactivated CMV-infection. CMV-R was found in 84, CMV-E in 65, CMV-A in 41 and CMV in the gastrointestinal tract in 21. Mycobacterial infection was found in 87 and toxoplasmosis in 29. Kaposi’s sarcoma was the most common tumour (68 cases) followed by 22 patients with malignant lymphoma and 20 with CNS-lymphoma. CMV-reactivation was seen in most diagnostic. A case of primary CMV-infection leading to a malignant lymphoma by interaction with two other herpes viruses was also seen. Conclusion: CMV-infection was the main OI in AIDS-patients during the pre-c-ART era and also the main cause of death by itself or together with other OIs. Reactivation of CMV was found in 87%. The most important CMV manifestations were CMV-R, CMV-E and CMV-A that seemed to occur at the same time. All of them have characteristic symptoms. Thus, when one of these is diagnosed investigation for the other two should be done. This is still today important in patients with CD4+ < 100 x 106/mL without access to modern HIV-treatment. These findings reveal the intimate interaction between HIV and CMV which should be considered in all co-infected patients also today.

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