Resistencia Trnasmitida e Adquirida do HIV no Brasil.

Apresentação em tema: "Resistencia Trnasmitida e Adquirida do HIV no 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
Site Population NNRTI NRTI PI Total MDR (Rio de Janeiro, RJ), Varella et al., J Med Virol , 79(8): 20 Recent infection (RI) 1.4% 52 cronic infection (CI) (Salvador, BA), Pedroso et all., JAIDS, 45(2), 2007, pp 130 cronic infection with 20 kids included 11.4% 9.8% 5% (Santos, SP) Sucupira et al., AIDS Patient Care STDS ,21(2): 25 RI  0 22,7%   13,6% 36.8 % 65 CI 15%   21,7% 8,1%  25% (Recife, PE) Medeiros et al., Mem Inst Oswaldo Cruz. 2006,101(8):845-9. 84 CI 3.6 (Rio de Janeiro, RJ ) Teixeira et al.; J. Med Virol Jun;78(6):764-9. 27 (1994-7) UDI 22% 31 ( ) UDI 13% 7.9% (Rio de Janeiro) Brindeiro et al. 2003 2,06% ,36% 2,24% (Sao Paulo, SP) Barreto et al., J Acquir Immune Defic Syndr. 2006, 41(3): 342 blood donors ( ) 6.3%; No change when ( ) is compared with ( ); IR MDR>IC MDR (Porto Alegre, RS) Rodrigues, R, Virus Res ;116(1-2):201-7 108 (2004-5) 2% 1% No MDR

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

12 Primary HIV DR in different countries using recent infected population
Study (place) n Definition of recent infection Year Prevalence REDADA 1 596 Clínico 10% CDC 2 182 STARHS * 12% San Francisco3 180 < 1 ano 26% North Caroline 4 30 < 30 dias 13% Canada†5 144 Montreal 6 170 France 7 296 < 6 meses 11% UK8 157 < 18 meses 17% Madrid 9 74 19% Zurich /Geneve 10 453

13 Primary HIV DR in different countries using cronic infected population
Estudo n year prevalence REDADA 1 379 7% CDC 2 900 Canada 3 378 5% France 4 363 2001 6% REINO UNIDO 5 1 966 14%

14 HIV DR Mutations impacting in RC (viral fitness)
11 9 5 17 RC * *Mutations Wrin T, 40th ICAAC 2000

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
Time to reach VL<500 copies/ml (USA) Susan Little et al. N Eng J Med, 2002 Time to reach VL<500 copies/ml in group with IC50<2,5 (low # of HIVDR) when compared with IC50>2,5

18 Time to show therapeutical failure Susan Little et al
Time to show therapeutical failure Susan Little et al. N Eng J Med, 2002 Time to show failure when the isolate has a IC50>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 Definición de líneas de tratamiento
Prescripción de ARV – pacientes que han iniciado TAR en 2012 ITRNN X IP ITRNN 66,2% IP 33,8% ITRNN Definición de líneas de tratamiento Nevirapina 6,7% Efavirenz 93,3% IP Lopinavir 64% Atazanavir 33% Fosamprenavir 3% ITRN AZT 71,2% TDF 27,6% ABC 0,8% 1ª línea: AZT X TDF

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

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

36 Pacientes >13 años Resistencia ITRN

37 Pacientes >13 años Resistencia ITRNN

38 Pacientes >13 años Resistencia IP

39 Pacientes >13 años Resistencia 3ª línea

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

45 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

49 RENIC2007/8 Characteristics

50 HIV-1 subtype prevalence in Brazil
RENIC2002 RENIC2007/8 New subtypes found in Brazil: CRF2-AG, and A.

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

52 HIV DR Mutations impacting in RC (viral fitness)
11 9 5 17 RC * *Mutations Wrin T, 40th ICAAC 2000