Cases inefficient antiretroviral therapy for HIV-1 in children
https://doi.org/10.22625/2072-6732-2017-9-2-72-79
Abstract
Aim. Study cases virologic failure ART HIV-1 in children.
Materials and methods. The blood plasma samples of 6 patients with HIV infection were used, identified under 1 year of life, from the North-West Federal District of the Russian Federation, received in 2014–2016. Presented in a group of patients were aimed at identifying drug resistance in the virus and correction of ART due to virological failure. In the present study we used genotyping by direct sequencing of the site of the polymerase gene (pol) length of 1285 nt., The gene encoding the protease (PR) length of 465 nt. and a portion of the reverse transcriptase (RT) gene length of 820 nt.
Results. In all cases, I was diagnosed with HIV-1 subtype A1, the so-called IDU-A, which is the most common form of HIV-1 in the Russian Federation. Among the obtained isolates of HIV have been identified typical drug resistance mutations to NRTI and NNRTI. Detected multiple natural polymorphic variants from the land of the nucleotide sequences. Thus, all samples show protease mutation M36I, R41K, H69K, and L89M, five samples E35D, four samples I13V. Only one among the surveyed our children with combined variant protease gene mutations L63T + V77I + I93L and reverse transcriptase gene V35I + K166R, despite ongoing therapy and absence of significant drug resistance mutations, according to Stanford University-based data showed high viral load – 2.03×107 copies/ml. The importance of the influence of natural polymorphisms in the drug resistance of the virus is discussed.
Conclusion. The high frequency of natural polymorphic variants of the protease and reverse transcriptase genes of the virus in clinical samples submitted. The number of such mutations, apparently does not depend on the number of treatment regimens, but found some correlation with adherence to treatment.
About the Authors
Yu. V. OstankovaRussian Federation
Saint-Petersburg
A. V. Semenov
Russian Federation
Saint-Petersburg
M. A. Churina
Russian Federation
Saint-Petersburg
A. A. Totolian
Russian Federation
Saint-Petersburg
References
1. Joint United Nations Programme on HIV/AIDS., United Nations. Global Report: UNAIDS Report on the Global AIDS epidemic: 2012. Geneva: UNAIDS; с 2012. 212 p.
2. The Federal Scientific and Methodological Center for Prevention and Control of AIDS FBUN Central Research Institute of Epidemiology. Reference «HIV infection in the Russian Federation on December 31, 2015. According to data provided by the regional centers for prevention and control of AIDS». 2015 (in Russian).
3. Hoffmann C., Rockstroh J.K. HIV Treatment 2009. R.Valent. Moscow; 2010 (in Russian).
4. Joint United Nations Programme on HIV/AIDS., United Nations. Global Report: UNAIDS Report on the Global AIDS epidemic: 2013. Geneva: UNAIDS; с 2013. 198 p.
5. Goosby E. The President’s Emergency Plan for AIDS Relief: marshalling all tools at our disposal toward an AIDS-free generation. Health Aff (Millwood). 2012 Jul; 31(7):1593-8.
6. Zeng H, Chow EP, Zhao Y, Wang Y, Tang M, Li L, Tang X, Liu X, Zhong Y, Wang A, Lo YR, Zhang L. Prevention of motherto-child HIV transmission cascade in China: a systematic review and meta-analysis. Sex Transm Infect. 2016 Mar; 92(2):116-23.
7. UNICEF. Progress for Children: Beyond Averages – Learning from the MDGs (No. 11). 2015 June; 68 p.
8. UNDP (United Nations Development Programme) World leaders adopt Sustainable Development Goals. Retrieved 2015 Sep.
9. On approval of the instruction on the prevention of HIV transmission from mother to child and sample informed consent for HIV chemoprophylaxis: Order of the RF Ministry of Health from 19.12.2003. №606. P. 126 (in Russian).
10. Prendergast AJ, Klenerman P, Goulder PJ. The impact of differential antiviral immunity in children and adults. Nat Rev Immunol. 2012 Sep; 12(9):636-48.
11. Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F; Ghent International AIDS Society (IAS) Working Group on HIV Infection in Women and Children. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet. 2004 Oct; 364(9441):1236-43.
12. Tobin NH, Aldrovandi GM. Immunology of pediatric HIV infection. Immunol Rev. 2013 Jul; 254(1):143-69.
13. Lowenthal ED, Bakeera-Kitaka S, Marukutira T, Chapman J, Goldrath K, Ferrand RA. Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges. Lancet Infect Dis. 2014 Jul;14(7):627-39.
14. Lederman MM, Calabrese L, Funderburg NT, Clagett B, Medvik K, Bonilla H, Gripshover B, Salata RA, Taege A, Lisgaris M, McComsey GA, Kirchner E, Baum J, Shive C, Asaad R, Kalayjian RC, Sieg SF, Rodriguez B. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J. Infect. Dis. 2011 Oct; 204(8):1217-26.
15. Rosenblatt HM, Stanley KE, Song LY, Johnson GM, Wiznia AA, Nachman SA, Krogstad PA; Pediatric AIDS Clinical Trials Group 377 Study Team. Immunological response to highly active antiretroviral therapy in children with clinically stable HIV-1 infection. J. Infect. Dis. 2005 Aug; 192(3):445-55.
16. World Health Organization, Department of Reproductive Health and Research. Male involvement in the prevention of mother-to-child transmission of HIV. Geneva: World Health Organization; c 2012. 30 p.
17. Cecchini DM, Zapiola I, Fernandez Giuliano S, Martinez MG, Rodriguez CG, Bouzas MB. Etravirine resistance mutations in HIV-infected pregnant women. HIV Med. 2013 Feb;14(2):125-6.
18. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov; 22(22):4673-80.
19. Update: vaccine side effects, adverse reactions, contraindications, and precautions. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1996 Sep; 45(RR-12):1-35.
20. Paraskevis D, Magiorkinis E, Magiorkinis G, Sypsa V, Paparizos V, Lazanas M, Gargalianos P, Antoniadou A, Panos G, Chrysos G, Sambatakou H, Karafoulidou A, Skoutelis A, Kordossis T, Koratzanis G, Theodoridou M, Daikos GL, Nikolopoulos G, Pybus OG, Hatzakis A; Multicentre Study on HIV Heterogeneity. Increasing prevalence of HIV-1 subtype A in Greece: estimating epidemic history and origin. J Infect Dis. 2007 Oct; 196(8):1167-76.
21. Manosuthi W, Thongyen S, Nilkamhang S, Manosuthi S, Sungkanuparph S. HIV-1 drug resistance-associated mutations among antiretroviral-naive Thai patients with chronic HIV-1 infection. J Med Virol. 2013; 85(2):194-9.
22. Sungkanuparph S, Sukasem C, Manosuthi W, Wiboonchutikul S, Piyavong B, Chantratita W. Tipranavir resistance associated mutations in protease inhibitor-na ve patients with HIV-1 subtype A/E infection. J Clin Virol. 2008 Nov; 43(3):284-6.
23. Davanos N, Panos G, Gogos CA, Mouzaki A. HIV-1 subtype characteristics of infected persons living in southwestern Greece. HIV AIDS (Auckl). 2015 Dec; 7:277-83.
24. Sutherland KA, Mbisa JL, Cane PA, Pillay D, Parry CM. Contribution of Gag and protease to variation in susceptibility to protease inhibitors between different strains of subtype B human immunodeficiency virus type 1. J Gen Virol. 2014 Jan; 95(Pt 1):190-200.
25. Alteri C, Artese A, Beheydt G, Santoro MM, Costa G, Parrotta L, Bertoli A, Gori C, Orchi N, Girardi E, Antinori A, Alcaro S, d’Arminio Monforte A, Theys K, Vandamme AM, Ceccherini-Silberstein F, Svicher V, Perno CF. Structural modifications induced by specific HIV-1 protease-compensatory mutations have an impact on the virological response to a firstline lopinavir/ritonavir-containing regimen. J Antimicrob Chemother. 2013 Oct; 68(10):2205-9.
26. Johnson VA, Brun-V zinet F, Clotet B, G nthard HF, Kuritzkes DR, Pillay D, Schapiro JM, Richman DD. Update of the drug resistance mutations in HIV-1: December 2010. Top HIV Med. 2010 Dec; 18(5):156-63.
27. Kazennova E.V. HIV and immunosuppression. 2010; 2 (3): 42-8 (in Russian).
28. Turriziani O, Russo G, Lichtner M, Stano A, Tsague G, Maida P, Vullo V, Antonelli G. Study of the genotypic resistant pattern in HIV-infected women and children from rural west Cameroon. AIDS Res Hum Retroviruses 2008 Jun; 24(6):781-5.
29. Kazennova E.V. HIV and immunosuppression. 2012; 4(4): 44-51 (in Russian).
30. Sukhanova A.L. Molecular Biology. 2005; 39(6):1063-71 (in Russian).
Review
For citations:
Ostankova Yu.V., Semenov A.V., Churina M.A., Totolian A.A. Cases inefficient antiretroviral therapy for HIV-1 in children. Journal Infectology. 2017;9(2):72-79. (In Russ.) https://doi.org/10.22625/2072-6732-2017-9-2-72-79