Novel approaches to etiological diagnosis of central nervous system lesions in patients with HIV

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Abstract

Objective. To identify the spectrum of central nervous system (CNS) lesions, by determining the detection rate and quantitative characteristics of the DNA of the causative agents of neuroinfections and RNA of the human immunodeficiency virus (HIV) in the cerebrospinal fluid (CSF) of inpatients with HIV infection.

Subjects and methods. Clinical observations were conducted in 5485 inpatients with HIV infection and their case histories were analyzed. Of these, 3333 patients had Stage 4B AIDS; 1310 patients had CNS lesions. The patients underwent contrast-enhanced brain MRI and diagnostic lumbar puncture. A total of 1667 CSF samples were studied using real time RT-PCR with the qualitative or quantitative determination of secondary disease pathogen DNA and HIV RNA. The reagent kits made by the Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, were used. The authors applied Statistica version 10.0 and SPSS version 20 statistical software packages, R was a programming language. Associations were examined by making a contingency table analysis using Pearson’s χ2 test. The significance level for the tested statistical hypotheses was taken equal to 0.05.

Results. The paper presents the quantitative measures of blood and CSF HIV RNA. Statistically significant associations were found between the blood and CSF HIV RNA levels. CNS lesions as encephalitis, meningoencephalitis, or meningitis were diagnosed in 1310 patients with HIV infection (23.8% of the total number of inpatients, 39.3% of those having Stage 4B AIDS, and 62.7% among the deceased). Among the patients with CNS lesions, there was a significant proportion (53.7%) of cases having encephalitis of unclear etiology. The presence of CSF neuroinfection pathogen DNA and HIV RNA were shown to have a high diagnostic sensitivity and the etiological role of the pathogen could be excluded in the absence of CSF. The qualitative detection of the DNAs of T. gondii, M. tuberculosis, C. neoformans, and human polyomavirus 2 (JCPyV) was shown to have a high diagnostic specificity. On the contrary, the fact of detecting the DNAs of cytomegalovirus, Epstein-Barr virus, human herpes virus type 6 (HHV-6 A/B type), fungi of the genus Candida, and HIV RNA was insufficient to confirm the etiological role of these pathogens in brain lesions. A wide CSF concentration range of these pathogens was established.in HIV-infected patients.

Conclusion. The absence of neuroinfection pathogen DNA and HIV RNA in the CSF excludes the corresponding etiology of brain damage. Detection of CSF T. gondii, M. tuberculosis, C. neoformans, or JCPyV DNAs confirms the nature of encephalitis. Quantitative determination should be used when examining CSF for EBV, CMV, HHV-6A/B, and Candida fungi DNAs and HIV RNA,

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About the authors

Vasily I. Shakhgildyan

МоCentral Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Author for correspondence.
Email: vishakh@yandex.ru
ORCID iD: 0000-0002-8686-0487

Cand. Med. Sci., Senior Researcher

Russian Federation, Moscow

Marina S. Yadrikhinskaya

Moscow City Center for AIDS Prevention and Control

Email: rusalo4ka_88@mail.ru
ORCID iD: 0000-0002-9649-8522

Resident

Russian Federation, Moscow

Elvira A. Domonova

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: elvira.domonova@pcr.ms
ORCID iD: 0000-0001-8262-3938

Cand. Biol. Sci. Head, Scientific Group for Development of New Methods for Diagnosing Opportunistic and Papillomavirus Infections, Department for Molecular Diagnosis and Epidemiology

Russian Federation, Moscow

Aleksey A. Orlovsky

M.V. Lomonosov Moscow State University

Email: leha-orl@yandex.by
ORCID iD: 0000-0002-0794-4683

Laboratory Researcher, Laboratory for Monitoring Programs for Reduction of Mortality from Cardiovascular Diseases, National Medical Research Center of Cardiology, Ministry of Health of Russia

Russian Federation, Moscow

Oleg A. Tishkevich

Clinical Infectious Diseases Hospital Two

Email: tishol@mail.ru
ORCID iD: 0000-0002-0789-7709

Pathologist, Clinical Infectious Diseases Hospital Two, Moscow City Healthcare Department

Russian Federation, Moscow

Elena B. Yarovaya

M.V. Lomonosov Moscow State University

Email: yarovaya@mech.math.msu.su

Pathologist, Clinical Infectious Diseases Hospital Two, Moscow City Healthcare Department

Russian Federation, Moscow

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2. Fig. 1. The spectrum and frequency of diseases occurring eith CNS damage in 5485 patients with different stages of HIV infection

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3. Fig. 2. The spectrum and frequency of diseases occurring eith CNS damage among 3333 patients with Stage 4B Infection (AIDS)

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4. Fig. 3. The spectrum and frequency of diseases occurring with CNS disease among HIV-infected patients with CNS lesion

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