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Resistencia Trnasmitida e Adquirida do HIV no Brasil. Amilcar Tanuri UFRJ, Brasil.

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Apresentação em tema: "Resistencia Trnasmitida e Adquirida do HIV no Brasil. Amilcar Tanuri UFRJ, Brasil."— Transcrição da apresentação:

1 Resistencia Trnasmitida e Adquirida do HIV no Brasil. Amilcar Tanuri UFRJ, Brasil

2 Tipos de Resistencia Resistencia Transmitida ou Primaria – Aquela que foi transmida de um individuo em uso de TARV para outro virgem de tratamento. Resistencia Secundaria – E aquela selecionada pelo uso de continuo ou nao de TARV

3 Como Contar a Resistencia Transmitida ?

4 Worldwide distribution of HIV-2, and HIV-1 subtypes and CRFs

5 Maneiras standarizadas para contar as Mutacoes Resistencia Shafer et al, Aids (2007) proposed a list where: –IP: 31 mutations in 14 positions. –NRTI: 31 mutations in 15 positions+ T215 revertants –NNRTI: 18 mutations in 10 positions.

6 List of protease mutations important for Surveillance

7 List of NRTI RTmutations important for Surveillance

8 List of NNRTI RTmutations important for Surveillance

9 O Site de Standford desenvolveu uma nova lista com as mutacoes balanceadas (CPR)

10 Primary Resistance in Brazil SitePopulationNNRTINRTIPITotal MDR (Rio de Janeiro, RJ), Varella et al., J Med Virol. 2007, 79(8): Recent infection (RI) 01.4%0 52 cronic infection (CI) (Salvador, BA), Pedroso et all., JAIDS, 45(2), 2007, pp cronic infection with 20 kids included 11.4%9.8%5% (Santos, SP) Sucupira et al., AIDS Patient Care STDS. 2007,21(2): RI 022,7% 13,6%36.8 % 65 CI15% 21,7%8,1% 25% (Recife, PE) Medeiros et al., Mem Inst Oswaldo Cruz. 2006,101(8): CI03.60 (Rio de Janeiro, RJ ) Teixeira et al.; J. Med Virol Jun;78(6): (1994-7) UDI22%0 31 ( ) UDI13%7.9% (Rio de Janeiro) Brindeiro et al ,06% 2,36%2,24% (Sao Paulo, SP) Barreto et al., J Acquir Immune Defic Syndr. 2006, 41(3): blood donors ( ) 6.3%; No change when ( ) is compared with ( ); IR MDR>IC MDR (Porto Alegre, RS) Rodrigues, R, Virus Res ;116(1-2): (2004-5)2%1%0No MDR

11 Tarnsmission of HIV DR strains among drug naive individuals with cronic infection (WATCH, 2006) Bowles E et al., 4 th EHDRW, Monte Carlo, March América do Norte 9.3% América do Norte 9.3% América Latina 5.0% América Latina 5.0% Overall rate = 8.9% (n=6054) Europa 11.3% Europa 11.3% África 5.7% África 5.7% Leste Asiático 9.4% Leste Asiático 9.4% S/SE Asia 5.3% S/SE Asia 5.3%

12 Primary HIV DR in different countries using recent infected population Study (place)n Definition of recent infection YearPrevalence REDADA 1 596Clínico % CDC 2 182STARHS * % San Francisco 3 180< 1 ano % North Caroline 4 30< 30 dias % Canada †5 144STARHS * % Montreal 6 170< 1 ano % France 7 296< 6 meses % UK 8 157< 18 meses % Madrid 9 74< 1 ano % Zurich /Geneve < 1 ano %

13 Primary HIV DR in different countries using cronic infected population Estudonyearprevalence REDADA % CDC % Canada % France % REINO UNIDO %

14 RC *Mutations * Wrin T, 40 th ICAAC 2000 HIV DR Mutations impacting in RC (viral fitness)

15 Tamanho amostral OMS THS

16 HIV prymary resistance and its impact in 1st line regimens.

17 Time to reach VL<500 copies/ml (USA) Susan Little et al. N Eng J Med, 2002 Time to reach VL 2,5

18 Time to show therapeutical failure Susan Little et al. N Eng J Med, 2002 Time to show failure when the isolate has a IC 50 >10 in the primary infection

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23 NGS aumentou a sensibilidade na identificacao das mutacoes Este aumento gerou muita controversia quanto o cut-off para considerar a mutacao relevante > ???% Tambem nao se sabe muito o impacto na resposta terapeutico. A analise fica mais confiavel junto com a analise do nivel da carga viral

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27 Como esta se Comportando as taxas de Resistencia Primarias no Mundo

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33 Prescripción de ARV – pacientes que han iniciado TAR en 2012 ITRNN X IP ITRNN66,2% IP33,8% ITRNN Nevirapina6,7% Efavirenz93,3% IP Lopinavir64% Atazanavir33% Fosamprenavir3% ITRN AZT71,2% TDF27,6% ABC0,8% Definición de líneas de tratamiento 1ª línea: AZT X TDF

34 Periodo: 2012 Genotipificaciones sin R o I = 14%

35 ITRN ITRNN IP 3ª línea Susceptible Resistente Pacientes >13 años

36 Resistencia ITRN Pacientes >13 años

37 Resistencia ITRNN Pacientes >13 años

38 Resistencia IP Pacientes >13 años

39 Resistencia 3ª línea Pacientes >13 años

40 Primero fracaso terapéutico: cambiar ITRN o ITRNN? Primero Fracaso Terapéutico: Resistencia a ITRN (Pacientes que han iniciado TAR con ITRNN, 2011 y 2012)

41 Primero Fracaso Terapéutico: cambiar ITRN o ITRNN? Primero Fracaso Terapéutico: Resistencia a ITRNN (Pacientes que han iniciado TAR con ITRNN, 2011 y 2012)

42 RENIC Study What is RENIC? Rede Nacional de Identificação e Caracterização do HIV. BRESNET Brazilian Resistance Network

43 RENIC/BRESNET Started in 2001 to study the HIV primary resistance in Brazil. 1st survey was done in 2002 targeting recent diagnosed patientes attending VCT sites spread in spanned metropolitan regions located in eight different Brazilian states, Rio Grande do Sul (n ¼ 139), Parana (n= 147), Sao Paulo (n = 100), Rio de Janeiro (n = 83), Mato Grosso do Sul (n = 7), Para (n ¼=17), Bahia (n = 12), and Ceara (n =30), that covered 65% of Brazilian AIDS Epidemic.

44 RENIC2002 Characteristics

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47 RENIC2007/8 Characteristics A new RENIC survey was placed in 2007/8. This done using the HIV Threshold Survey methodology (HIV-THS, WHO), targeting the four major Brazilian regions, selecting the 6 more populated state capitals, Sao Paulo, Rio de Janeiro, Salvador, Porto Alegre, Brasilia, and Belem. We were able to sequence samples from 210 individuals with recent HIV diagnosis, 17 of them (8.1%) carrying HIV isolates with primary antiretroviral resistance mutations. Five, nine, and four isolates showed mutations related to resistance to NRTIs, NNRTIs, and PIs, respectively. Using HIV-THS we could find an intermediate level of resistance (5%-15%) in Belem/Brasilia, Sao Paulo and Rio de Janeiro, whereas lower level of resistance (<5%) was observed in the other areas.

48 RENIC2007/8 Characteristics

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50 HIV-1 subtype prevalence in Brazil RENIC2002RENIC2007/8 New subtypes found in Brazil: CRF2-AG, and A.

51 Primary resistance trend in Brazil Comparing RENIC 02 X 07/8

52 RC *Mutations * Wrin T, 40 th ICAAC 2000 HIV DR Mutations impacting in RC (viral fitness)


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