Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals

Monica B Arruda, Lídia T Boullosa, Cynthia C Cardoso, Carolina M da Costa, Carlos Rb Alves, Shirlene Ts de Lima, Helena T Kaminski, Agdemir W Aleixo, Ana Op Esposito, Ana Ms Cavalcanti, Maristela Riedel, José C Couto-Fernandez, Selma B Ferreira, Ivi Cm de Oliveira, Loreci E Portal, Hilda Hc Wolf, Sandra B Fernandes, Maria I de M C Pardini, Manoel Vc Feiteiro, Fernanda M Tolentino, Ricardo S Diaz, Giselle Isl Lopes, Roberta Bl Francisco, Nazle Mc Véras, Ana F Pires, Miriam Franchini, Fábio Mesquita, Amilcar Tanuri, HIV-BResNet, Andrea de Melo Xavier Shimizu, Célia Regina Mayoral Pedroso Jorge, Leda Maria Simões Mello, Eider Gurgel de Freitas, Unaí Tupinambás, Dijane Cristina de Barros Rosa Costa, Sirleide Pereira da Silva, Maria da Graça Winhescki, Carlos Silva de Jesus, Érica Ramos Dos Santos Nascimento, Fatima Ercília de Oliveira Prazim, Marilda Tereza Mar da Rosa, Karina Salvador, Senele Ana de Alcântara Belettini, Rejane Maria Tommasini Grotto, Paulo Henrique de Oliveira, Érica Valessa Ramos Gomes, Danilo Araujo Dias, Juliana Galinskas, Norberto Camilo Campos, José Boullosa Alonso Neto, Monica B Arruda, Lídia T Boullosa, Cynthia C Cardoso, Carolina M da Costa, Carlos Rb Alves, Shirlene Ts de Lima, Helena T Kaminski, Agdemir W Aleixo, Ana Op Esposito, Ana Ms Cavalcanti, Maristela Riedel, José C Couto-Fernandez, Selma B Ferreira, Ivi Cm de Oliveira, Loreci E Portal, Hilda Hc Wolf, Sandra B Fernandes, Maria I de M C Pardini, Manoel Vc Feiteiro, Fernanda M Tolentino, Ricardo S Diaz, Giselle Isl Lopes, Roberta Bl Francisco, Nazle Mc Véras, Ana F Pires, Miriam Franchini, Fábio Mesquita, Amilcar Tanuri, HIV-BResNet, Andrea de Melo Xavier Shimizu, Célia Regina Mayoral Pedroso Jorge, Leda Maria Simões Mello, Eider Gurgel de Freitas, Unaí Tupinambás, Dijane Cristina de Barros Rosa Costa, Sirleide Pereira da Silva, Maria da Graça Winhescki, Carlos Silva de Jesus, Érica Ramos Dos Santos Nascimento, Fatima Ercília de Oliveira Prazim, Marilda Tereza Mar da Rosa, Karina Salvador, Senele Ana de Alcântara Belettini, Rejane Maria Tommasini Grotto, Paulo Henrique de Oliveira, Érica Valessa Ramos Gomes, Danilo Araujo Dias, Juliana Galinskas, Norberto Camilo Campos, José Boullosa Alonso Neto

Abstract

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015.

Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing.

Results: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails.

Conclusions: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.

Keywords: HIV; HIV Drug Resistance Surveillance; HIV drug resistance; antiretroviral resistance; pretreatment HIV drug resistance; primary antiretroviral resistance.

© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Figures

Figure 1
Figure 1
Prevalence of sequences with any SDRM (surveillance drug‐resistance mutation), any nucleoside reverse transcriptase inhibitors (NRTI) SDRM, any non‐nucleoside reverse transcriptase inhibitors (NNRTI) SDRM and protease inhibitors (PI) SDRM distributed throughout all five geographical regions in Brazil: north, northeast, central‐west, southeast, and south.
Figure 2
Figure 2
Prevalence of drug resistance mutations by drug class in antiretroviral drug‐naive patients in each of the five geographical regions. (a) nucleoside reverse transcriptase inhibitors (NRTI) (b) non‐nucleoside reverse transcriptase inhibitors (NNRTI) and (c) protease inhibitors (PI).
Figure 3
Figure 3
Distribution of subtypes throughout Brazil's five geographical regions. The map shows the distribution of subtype based on PR and RT genomic regions as well CRFs and URFs.

References

    1. Teixeira PR, Vitória MA, Barcarolo J. Antiretroviral treatment in resource‐poor settings: the Brazilian experience. AIDS. 2004;18 Suppl 3:S5–7.
    1. Pennings PS. HIV drug resistance: problems and perspectives. Infect Dis Rep. 2013;5 Suppl 1:e5.
    1. Gagliani LH, Alkmim Maia WT, Sá‐Filho D, Janini LM, Sucupira MC, Caseiro MM, et al. The association between primary antiretroviral resistance and HAART virologic failure in a developing set. AIDS Res Hum Retroviruses. 2011;27(3):251–6.
    1. Frentz D, Boucher CA, van de Vijver DA. Temporal changes in the epidemiology of transmission of drug‐resistant HIV‐1 across the world. AIDS Rev. 2012;14(1):17–27.
    1. Yang WL, Kouyos RD, Böni J, Yerly S, Klimkait T, Aubert V, et al. Persistence of transmitted HIV‐1 drug resistance mutations associated with fitness costs and viral genetic backgrounds. PLoS Pathog. 2015;11(3):e1004722.
    1. Readhead AC, Gordon DE, Wang Z, Anderson BJ, Brousseau KS, Kouznetsova MA, et al. Transmitted antiretroviral drug resistance in New York State, 2006‐2008: results from a new surveillance system. PLoS One. 2012;7(8):e40533.
    1. Karlsson A, Björkman P, Bratt G, Ekvall H, Gisslén M, Sönnerborg A, et al. Low prevalence of transmitted drug resistance in patients newly diagnosed with HIV‐1 infection in Sweden 2003‐2010. PLoS One. 2012;7(3):e33484.
    1. Temereanca A, Ene L, Mehta S, Manolescu L, Duiculescu D, Ruta S. Transmitted HIV drug resistance in treatment‐naive Romanian patients. J Med Virol. 2013;85(7):1139–47.
    1. Vega Y, Delgado E, Fernández‐García A, Cuevas MT, Thomson MM, Montero V, et al. Epidemiological surveillance of HIV‐1 transmitted drug Resistance in Spain in 2004‐2012: relevance of transmission clusters in the propagation of resistance mutations. PLoS One. 2015;10(5):e0125699.
    1. Neogi U, Sahoo PN, De Costa A, Shet A. High viremia and low level of transmitted drug resistance in anti‐retroviral therapy‐naïve perinatally‐infected children and adolescents with HIV‐1 subtype C infection. BMC Infect Dis. 2012;12:317.
    1. Ssemwanga D, Lihana RW, Ugoji C, Abimiku A, Nkengasong J, Dakum P, et al. Update on HIV‐1 acquired and transmitted drug resistance in Africa. AIDS Rev. 2015;17(1):3–20.
    1. Brindeiro RM, Diaz RS, Sabino EC, Morgado MG, Pires IL, Brigido L, et al. Brazilian Network for HIV Drug Resistance Surveillance (HIV‐BResNet): a survey of chronically infected individuals. AIDS. 2003;17(7):1063–9.
    1. Inocencio LA, Pereira AA, Sucupira MC, Fernandez JC, Jorge CP, Souza DF, et al. Brazilian Network for HIV Drug Resistance Surveillance: a survey of individuals recently diagnosed with HIV. J Int AIDS Soc. 2009;12:20.
    1. World Health Organization . Surveillance of HIV drug resistance in adults initiating antiretroviral therapy(pre‐treatment HIV drug resistance). Switzerland: World Health Organization; 2014. 36 p.
    1. Souza DC, Sucupira MC, Brindeiro RM, Fernandez JC, Sabino EC, Inocencio LA, et al. The Brazilian network for HIV‐1 genotyping external quality control assurance programme. J Int AIDS Soc. 2011;14:45.
    1. Gifford RJ, Liu TF, Rhee SY, Kiuchi M, Hue S, Pillay D, et al. The calibrated population resistance tool: standardized genotypic estimation of transmitted HIV‐1 drug resistance. Bioinformatics. 2009;25(9):1197–8.
    1. Bennett DE, Bertagnolio S, Sutherland D, Gilks CF. The World Health Organization's global strategy for prevention and assessment of HIV drug resistance. Antivir Ther. 2008;13 Suppl 2:1–13.
    1. Liu TF, Shafer RW. Web resources for HIV type 1 genotypic‐resistance test interpretation. Clin Infect Dis. 2006;42(11):1608–18.
    1. de Oliveira T, Deforche K, Cassol S, Salminen M, Paraskevis D, Seebregts C, et al. An automated genotyping system for analysis of HIV‐1 and other microbial sequences. Bioinformatics. 2005;21(19):3797–800.
    1. Alcantara LC, Cassol S, Libin P, Deforche K, Pybus OG, Van Ranst M, et al. A standardized framework for accurate, high‐throughput genotyping of recombinant and non‐recombinant viral sequences. Nucleic Acids Res. 2009;37 Web Server issue: W634–42.
    1. Brazil. Brazilian Ministry of Health . Epidemiological Bulletin for HIV/AIDS In: A.e.H.V , editor. Boletim Epidemiológico ‐ Aids e DST. Brasília: Secretaria de Vigilância em Saúde. Departamento de DST; 2015. p. 21–2.
    1. Pedroso C, Queiroz AT, Alcântara LC, Drexler JF, Diaz RS, Weyll N, et al. High prevalence of primary antiretroviral resistance among HIV‐1‐infected adults and children in Bahia, a northeast state of Brazil. J Acquir Immune Defic Syndr. 2007;45 2:251–3.
    1. de Moraes Soares CM, Vergara TR, Brites C, Brito JD, Grinberg G, Caseiro MM, et al. Prevalence of transmitted HIV‐1 antiretroviral resistance among patients initiating antiretroviral therapy in Brazil: a surveillance study using dried blood spots. J Int AIDS Soc. 2014;17:19042.
    1. Guimarães PM, Ferreira JL, Coelho LP, Cavalcanti Jde S, Lopes GI, Matsuda EM, et al. Transmitted drug resistance among recently diagnosed adults and children in São Paulo, Brazil. AIDS Res Hum Retroviruses. 2015;31(12):1219–24.
    1. Sucupira MC, Caseiro MM, Alves K, Tescarollo G, Janini LM, Sabino EC, et al. High levels of primary antiretroviral resistance genotypic mutations and B/F recombinants in Santos, Brazil. AIDS Patient Care STDS. 2007;21(2):116–28.
    1. Bissio E, Barbás MG, Bouzas MB, Cudolá A, Salomón H, Espínola L, et al. Pretreatment HIV‐1 drug resistance in Argentina: results from a surveillance study performed according to WHO‐proposed new methodology in 2014‐15. J Antimicrob Chemother. 2017;72(2):504–10.
    1. Rhee SY, Blanco JL, Jordan MR, Taylor J, Lemey P, Varghese V, et al. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV‐1 drug resistance: an individual‐patient‐ and sequence‐level meta‐analysis. PLoS Med. 2015;2(4):e1001810.
    1. Jain V, Sucupira MC, Bacchetti P, Hartogensis W, Diaz RS, Kallas EG, et al. Differential persistence of transmitted HIV‐1 drug resistance mutation classes. J Infect Dis. 2011;203(8):1174–81.
    1. Garcia‐Lerma JG, Nidtha S, Blumoff K, Weinstock H, Heneine W. Increased ability for selection of zidovudine resistance in a distinct class of wild‐type HIV‐1 from drug‐naive persons. Proc Natl Acad Sci USA. 2001;98(24):13907–12.
    1. Violin M, Cozzi‐Lepri A, Velleca R, Vincenti A, D'Elia S, Chiodo F, et al. Risk of failure in patients with 215 HIV‐1 revertants starting their first thymidine analog‐containing highly active antiretroviral therapy. AIDS. 2004;18(2):227–35.
    1. Soares MA, De Oliveira T, Brindeiro RM, Diaz RS, Sabino EC, Brigido L, et al. A specific subtype C of human immunodeficiency virus type 1 circulates in Brazil. AIDS. 2003;17(1):11–21.
    1. Diaz RS, Inocêncio LA, Sucupira MC, Pereira AA, Hunter J, Ferreira JE, et al. The virological and immunological characteristics of the HIV‐1‐infected population in Brazil: from initial diagnosis to impact of antiretroviral use. PLoS One. 2015;10(10):e0139677.
    1. Leal É, Martins LO, Janini LM, Diaz RS. Evolutionary dynamics of HIV‐1 BF and CB recombinants and its parental counterparts in South America. Retrovirology. 2008;1:1–14.
    1. Bello G, Passaes CP, Guimarães ML, Lorete RS, Matos Almeida SE, Medeiros RM, et al. Origin and evolutionary history of HIV‐1 subtype C in Brazil. AIDS. 2008;22(15):1993–2000.
    1. Passaes CP, Bello G, Lorete RS, Matos Almeida SE, Junqueira DM, Veloso VG, et al. Genetic characterization of HIV‐1 BC recombinants and evolutionary history of the CRF31_BC in Southern Brazil. Infect Genet Evol. 2009;9(4):474–82.
    1. Sucupira MC, Munerato P, Silveira J, Santos AF, Janini LM, Soares MA, et al. Phenotypic susceptibility to antiretrovirals among clades C, F, and B/F recombinant antiretroviral‐naive HIV type 1 strains. AIDS Res Hum Retroviruses. 2013;29(6):880–6.

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