COMPARATIVE EVALUATION OF THE 4TH GENERATION ELISA/CLIA ASSAYS USED FOR THE DIAGNOSIS OF HIV INFECTION IN THE RUSSIAN FEDERATION

The aim of the work was to compare the five most widely used ELISA diagnostic kits on the territory of the Russian Federation, which are used for screening for HIV infection.

Materials and methods. 5442 samples from visitors of diagnostic centers who came for blood donation for non-infectious analyses, cohorts with a high risk of HIV infection, as well as patients with potentially interfering conditions were used as a material for the study. Additionally, seroconversion panels and a panel of viral diversity were used to evaluate the analytical characteristics. The following test systems were compared: Architect HIV Ag/Ab Combo (Abbott), Genscreen Ultra HIV Ag-Ab (Bio-Rad), CombiBest HIV-1,2 AG/AT (Vector-Best), DS-ELISA-HIVAGAT-SCREEN (Diagnostic Systems), HIV-1,2-AG/AT (Medical-Biological Union).

Conclusion. The diagnostic sensitivity of all tests was 100% with the exception of one (Medical-Biological Union), in which it turned out to be 99,54%. Diagnostic specificity ranged from 99,58% to 99,89%, but unexpectedly strongly depended on the test population, decreasing on a group with a high risk of HIV infection to 93,26% (Vector-Best). The convergence between initial and repeat reactive samples ranged from 100% (Abbott) to 89,51% (Vector-Best). The results of the analysis of seroconversion panels showed that the tests differed slightly from each other, receiving positive results from 22,12% (Diagnostic Systems) to 27,88% (Abbott) samples. When testing the panel of viral diversity, diagnostic tests from foreign manufacturers showed better results, revealing 100% (Abbott) and 85,9% (Bio-Rad). The smallest number of panel samples was detected by the kit of the Medical-Biological Union (52,1%). This work is the only study where the 4th generation ELISA kits, widely used in the Russian Federation for screening for HIV infection, were compared in an extensive sampling. The results obtained make it possible to evaluate the effectiveness of the use of the listed kits in routine diagnostic practice.

1. UNAIDS data 2018. URL: http://www.unaids.org/sites/default/files/media_asset/unaids-data-2018_en.pdf.

2. Санитарно-эпидемиологические правила СП 3.1.5.2826–10 «Профилактика ВИЧ-инфекции» (ред. от 21.07.2016) / Постановление Главного государственного санитарного врача РФ от 21.07.2016 № 95. М., 2016. [Sanitary and epidemiological rules SP 3.1.5.2826–10 «Prevention of HIV infection» (ed. from 21.07.2016). Resolution of the Chief state sanitary doctor of the Russian Federation from 21.07.2016 № 95. Moscow, 2016 (In Russ.)].

3. ВИЧ-инфекция: Информационный бюллетень № 43. М.: ФНМЦ по профилактике и борьбе со СПИДом ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора, 2018. [HIV infection: Information Bulletin № 43. Moscow: Federal scientific and methodological center for AIDS prevention and control Central research Institute «Central research Institute of epidemiology» of Rospotrebnadzor, 2018 (In Russ)].

4. Hemelaar J. Implications of HIV diversity for the HIV-1 pandemic. J. Infect., 2013 May, Vol. 66, No. 5, pp. 391–400. URL: DOI: 10.1016/j.jinf.2012.10.026.

5. Gaudy C., Moreau A., Brunet S., Descamps J.M., Deleplanque P., Brand D., Barin F. Subtype B human immunodeficiency virus (HIV) type 1 mutant that escapes detection in a fourth generation immunoassay for HIV infection. J. Clin. Microbiol., 2004, Vol. 42, pp. 2847–2849. 6. Ly T.D., Plantier J.C., Leballais L., Gonzalo S., Lemée V., Laperche S. The variable sensitivity of HIV Ag/Ab combination assays in the detection of p24 Ag according to genotype could compromise the diagnosis of early HIV infection. J. Clin. Virol., 2012, Vol. 55, pp. 121–127. URL: DOI: 10.1016/j.jcv.2012.06.012.

6. Qiu X., Sokoll L., Yip P., Elliott D.J., Dua R., Mohr P., Wang X.Y., Spencer M., Swanson P., Dawson G.J., Hackett J. Jr. Comparative evaluation of three FDA-approved HIV Ag/Ab combination tests using a genetically diverse HIV panel and diagnostic specimens.J. Clin. Virol., 2017 Jul., Vol. 92, pp. 62–68. URL: DOI: 10.1016/j.jcv.2017.05.005.

7. Баранова Е.Н., Шарипова И.Н., Денисова Н.М., Сусекина М.Е., Пузырев В.Ф., Саркисян К.А., Воробьева М.С., Бурков А.Н., Уланова Т.И. Возможности современных тест-систем при подтверждении ранней ВИЧ-инфекции // Вопросы вирусологии. 2009. Т. 54, № 5. С. 37–40. [Baranova E.N., Sharipova I.N., Denisova N.M. Susekina M.E., Puzyrev V.F., Sarkisyan K.A., Vorobyeva M.S., Burkov A.N., Ulanova T.I. The possibilities of modern test systems for the early confirmation of HIV infection. Questions of Virology, 2009, Vol. 54, No. 5, pp. 37–40 (In Russ.)].

8. Иванова Н.И., Пекшева О.Ю. Опыт выявления маркеров ВИЧ-инфекции с использованием нового ИФА-диагностикума ДС-ИФА-ВИЧ-АТ/АГ-СПЕКТР в лабораториях центров по профилактике и борьбе со СПИДом Приволжского Федерального округа // Клиническая лабораторная диагностика. 2009. № 3. С. 46–48. [Ivanova N.I., Peksheva O.Yu. Experience identifying markers of HIV with the new ELISA antigen of DS-ELISA-HIV-at/AG-SPECTRUM in the laboratories of the centers for the prevention and control of AIDS of the Volga Federal district. Clinical Laboratory Diagnostics, 2009, No. 3, pp. 46–48 (In Russ.)].

9. Распопина И.В., Панкова Л.В., Кожевникова И.В. Опыт выявления маркёров ВИЧ-инфекции с использованием нового ИФА-диагностикума Инвитролоджик ВИЧ 1,2-АГ/АТ // Вестник Челябинской областной клинической больницы. 2013. № 1 (20). С. 84. [Raspopina I.V., Pankova L.V., Kozhevnikov I.V. Experience of identifying markers of HIV with the new ELISA antigen of Envitrologic HIV-1,2-AG/AT. Bulletin of the Chelyabinsk Regional Clinical Hospital, 2013, No. 1 (20), pp. 84 (In Russ.)].

10. Шарипова И.Н., Ходак Н.М., Пузырев В.Ф., Бурков А.Н., Уланова Т.И. Сравнительное исследование специфичности тест-систем для диагностики ВИЧ-инфекции на категории образцов сывороток крови беременных женщин // Клиническая лабораторная диагностика. 2015. Т. 60, № 3. С. 38–41. [Sharipova I.N., Khodak N.M. Puzyrev V.F., Burkov A.N., Ulanova T.I. Comparative study of the specificity of test systems for the diagnosis of HIV infection in the category of blood serum samples of pregnant women. Clinical Laboratory Diagnostics, 2015, Vol. 60, No. 3, pp. 38–41 (In Russ.)].

11. Лисицина З.Н., Дмитриевская К.А., Коробан Н.В., Кондрашова Т.В. Иммунные тесты и диагностика острой стадии ВИЧ-инфекции // ВИЧ-инфекция и иммуносупрессии. 2017. Т. 9, № 2. С. 36–41. [Lisitsina Z.N., Dmitrievskaya K.A., Koroban N.V., Kondrashova T.V. Immune tests and diagnosis of the acute stage of HIV infection. HIV Infection and Immunosuppressive Disorders, 2017, Vol. 9, No. 2, pp. 36–41 (In Russ.)].

12. HIV assays: laboratory performance and other operational characteristics: rapid diagnostic tests (combined detection of HIV-1/2 antibodies and discriminatory detection of HIV-1 and HIV-2 antibodies): report 18. Geneva: World Health Organization, 2015.

13. Chaves P., Wesolowski L., Patel P., Delaney K., Owen S.M. Evaluation of the performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay. J. Clin. Virol., 2011 Dec., Vol. 52, Suppl. 1, pp. S51–S55. URL: DOI: 10.1016/j.jcv.2011.09.010.

14. Mitchell E.O., Stewart G., Bajzik O., Ferret M., Bentsen C., Shriver M.K. Performance comparison of the 4-th generation Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA on the EVOLIS™ automated system versus Abbott ARCHITECT HIV Ag/Ab Combo, Ortho Anti-HIV 1+2 EIA on Vitros ECi and Siemens HIV-1/O/2 enhanced on Advia Centaur.J. Clin. Virol., 2013 Dec., Vol. 58, Suppl. 1, pp. e79–e84. URL: DOI: 10.1016/j.jcv.2013.08.009. 16. Product Package Insert. ARCHITECT HIV Ag/Ab Combo Reagent Kit. USA: Abbott Laboratories.

15. Инструкция по применению ИФА тест-системы «Дженскрин Ультра ВИЧ Aг/Aт». Франция: Bio-Rad. [Instructions for use of ELISA test system Genscreen Ultra HIV AG/AТ. France: Bio-Rad (In Russ.)].

16. Инструкция по применению набора реагентов «ДС-ИФА-ВИЧ-АГАТ-СКРИН». Нижний Новгород: ООО «Диагностические системы». [Instructions for use of a set of reagents «DS-IFA-VICH-AGATHE-SCREEN». Nizhny Novgorod: Diagnostic systems (In Russ.)].

17. Лаповок И.А., Лопатухин А.Э., Киреев Д.Е. и др. Молекулярно-эпидемиологический анализ вариантов ВИЧ-1, циркулировавших в России в 1987–2015 гг. // Терапевтический архив. 2017. Т. 89, № 11. С. 44–49. [Lapovok I.A., Lopatukhin A.E., Kireev D.A. et al. Molecular epidemiological analysis of HIV-1 circulating in Russia in the years 1987–2015. Therapeutic Archive, 2017, Vol. 89, No. 11, pp. 44–49 (In Russ.)]