Pattern of secondary diseases and current approaches to their laboratory diagnosis in patients with HIV infection

Objective. To determine the pattern of secondary diseases in HIV-infected patients from the Infectious Diseases Hospital and to establish the rate and quantitative characteristics of detection of DNA of opportunistic pathogens in the patients’ biological materials. Subjects and methods. 1333 (85.5%) inpatients with stage 4B-4C HIV infection (AIDS) were examined. CD4+-lymphocyte counts of < 200 cells/μl were found in 70% of the patients. 2456 biological materials (blood, bronchoalveolar lavage (BALF), cerebrospinal (CSF), and pleural fluid samples and biopsy specimens) were investigated for the presence and quantification of M. tuberculosis, C. albicans, С. glabrata, C. cruzei, C. neoformins, T. gondii, cytomegalovirus (CMV), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), human herpesvirus type 6 (HHV-6), Epstein-Barr virus (EBV), and JC virus DNA and HIV RNA by molecular techniques using the polymerase chain reaction systems made at the Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare. Results. The most common secondary diseases were tuberculosis, esophageal candidiasis, obvious CMV infection, toxoplasmosis, and Pneumocystis pneumonia. There was a rise in the incidence of HIV encephalitis, cryptococcal meningitis, atypical mycobacteriosis, multifocal leukoencephalopathy, and lymphomas. According to the biological material, the sensitivity of Mycobacterium tuberculosis DNA in the patients with tuberculosis was 44.8-93.7% with 100% specificity. The CMV nature of organic diseases was supported by the detection of CMV DNA of 2.0 lg in the leukocytes and > 10,000 copies/ml in the plasma, and cytomegalic cells in the biopsy and autopsy specimens. The presence of CMV DNA of >10,000 copies/ml in BALF or CSF was of diagnostic value. The value of the qualitative and quantitative detection of herpesvirus (HSV-1, HHV-6, varicella zoster virus) DNA in the biological materials in diagnosing herpesvirus-induced visceral involvement calls for further investigations. EBV was the most frequently detected pathogen in any biological material with copy numbers ranging from tens to millions. The virus DNA concentration of > 10,000 copies/ml in CSF may be indicative of primary brain lymphoma. The diagnostic sensitivity of the presence of T. gondii DNA in CSF was equal to 43% with 100% specificity. The detection of the high and moderate concentrations of anti-T gondii IgG antibodies were of diagnostic value. The presence of JC virus in CSF is a determining factor to verify the diagnosis of multifocal leukoencephalopathy. It is necessary to quantify the content of DNA of the pathogen in the sputum and BALF in order to establish the mycotic etiology of lung injury. In cryptococcal meningitis, the detection of C. neoformins DNA in CSF has 100% sensitivity and 100% specificity. In patients with HIV infection, besides CMV encephaloventroculitis and multifocal leukoencephalopathy, neurocognitive impairments may be associated with HIV encephalitis, which necessitates the determination of the presence and concentration of HIV RNA in CSF. Conclusion. Molecular biological techniques for detection of opportunistic pathogens in HIV-infected patients play a central role in making an etiological diagnosis in due time.

polymerase chain reaction, Mycobacterium tuberculosis DNA, cytomegalovirus infection