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Resistencia Trnasmitida e Adquirida do HIV no Brasil.

Resistencia Trnasmitida e Adquirida do HIV no Brasil. Amilcar Tanuri UFRJ, Brasil. Tipos de Resistencia. Resistencia Transmitida ou Primaria – Aquela que foi transmida de um individuo em uso de TARV para outro virgem de tratamento.

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Resistencia Trnasmitida e Adquirida do HIV no Brasil.

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  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 Standforddesenvolveuuma nova lista com as mutacoesbalanceadas (CPR)

  10. Primary Resistance in Brazil

  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

  13. Primary HIV DR in different countries using cronic infected population

  14. HIV DR Mutations impacting in RC (viral fitness) 11 9 5 17 RC * *Mutations 41 + 67 + 70 + 215 +219 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 in group with IC50<2,5 (low # of HIVDR) when compared with IC50>2,5 Time to reach VL<500 copies/ml(USA)Susan Little et al. N Eng J Med, 2002

  18. Time to show failure when the isolate has a IC50>10 in the primary infection Time to show therapeutical failureSusan Little et al. N Eng J Med, 2002

  19. NGS aumentou a sensibilidadenaidentificacao das mutacoes • Este aumentogeroumuitacontroversiaquanto o cut-off para considerar a mutacaorelevante > ???% • Tambemnao se sabemuito o impactonarespostaterapeutico. • A analiseficamaisconfiaveljunto com a analise do nivel da carga viral

  20. Como esta se Comportando as taxas de Resistencia Primarias no Mundo

  21. Prescripción de ARV – pacientes que han iniciado TAR en 2012 ITRNN X IP Definición de líneas de tratamiento ITRNN IP ITRN 1ª línea: AZT X TDF

  22. Periodo: 2012 Genotipificaciones sin R o I = 14%

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

  24. Pacientes >13 años Resistencia ITRN

  25. Pacientes >13 años Resistencia ITRNN

  26. Pacientes >13 años Resistencia IP

  27. Pacientes >13 años Resistencia 3ª línea

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

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

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

  31. 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.

  32. RENIC2002 Characteristics

  33. RENIC2002 Characteristics

  34. 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.

  35. RENIC2007/8 Characteristics

  36. RENIC2007/8 Characteristics

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

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