interpretaci n de resistencias de las mutaciones a la cl nica l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Interpretación de Resistencias. De las mutaciones a la clínica. PowerPoint Presentation
Download Presentation
Interpretación de Resistencias. De las mutaciones a la clínica.

Loading in 2 Seconds...

play fullscreen
1 / 30

Interpretación de Resistencias. De las mutaciones a la clínica. - PowerPoint PPT Presentation


  • 95 Views
  • Uploaded on

Interpretación de Resistencias. De las mutaciones a la clínica. Carmen de Mendoza Servicio de Enfermedades Infecciosas Hospital Carlos III, Madrid. M41L & T215Y. History of HIV Drug Resistance. AZT (1986). HAART (1996). Genetic Barrier and Antiviral Potency. Resistance mutations

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Interpretación de Resistencias. De las mutaciones a la clínica.' - arich


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
interpretaci n de resistencias de las mutaciones a la cl nica

Interpretación de Resistencias. De las mutaciones a la clínica.

Carmen de Mendoza

Servicio de Enfermedades Infecciosas

Hospital Carlos III, Madrid.

slide3

Genetic Barrier

and Antiviral Potency

Resistance mutations

and patterns

Cross-Resistance

Surveillance

Comprehensive Drug Resistance Overview

the equation for arv success

inhibitory activity

  • genetic barrier

HIV-RNA

The equation for ARV success

Success of ARV= Potency x Convenience

  • pill burden
  • toxicity profile
first line therapy plan for success but prepare for failure
First - line therapyPlan for Success, but Prepare for Failure

- Prove that primary drug resistance are not present.

- Choose regimens with proven efficacy, tolerabilityand convenience to support adherence.

- Consider the implications of a failing regimen’s resistanceon:

  • Cross-resistance mutations
  • The availability of future effective options
slide6

Primary Genotypic Resistance Summary

Transmission of drug resistance viruses consistently are around 10-15% in HIV infected individuals with recent infection and in newly diagnosed with unknown time of infection

slide7

Prevalencia de mutaciones por familias de fármacos en Seroconvertores recientes por VIH en España

De Mendoza C, et al. Clin Infect Dis 2005; 41: 1350-4

slide8

Resistencia a NRTI

Resistencia a NNRTI

Multirresistencia

2000

2005

año

Tendencias en la transmisión de virus resistentes

baseline resistance predicts antiviral response in clinical cohort
Baseline Resistance Predicts Antiviral Response in Clinical Cohort
  • Retrospective analysis of resistance test results of samples taken from 1969 patients when treatment naive
  • As expected, baseline mutations associated with reduced response

*L100F, K103N, V106A/I, V108I, F116Y, Y181C, G190A/S, M230L.

†D30N, G48V, I50V, V82A/L/T, I84V, L90M.

‡P < .001 for reduced response to NNRTI in patients with NNRTI resistance vs no NNRTI resistance.

§P = .026 for increased response to NNRTI vs PI in patients with PI resistance.

Price H, et al. IAS 2007. Abstract TUPEB043.

long term risk of developing drug resistance

Time to Multiclass Resistance

% with resistance

Long-term risk of developing drug resistance
  • Risk of developing ARV drug resistance from the UK CHIC Study (n= 4306)
    • Longitudinal cohort from 6 clinics in London
    • Started ARV therapy with 2 NRTIs plus a 3rd agent
  • Overall risk of treatment failure was 38% over 6 years
  • Risk of accumulation resistance mutations to any drug 27%

Phillips et al. AIDS 2005; 19: 487-94

accumulation of resistance mutations

Viral

load

1st regimen

late

2nd regimen

intermediate

early

Time

Accumulation of resistance mutations

Increasing Resistance

hospital carlos iii arv failure

1328

No. of patients on HAART

1005

83%

80%

No. of patients with

plasma HIV-RNA <50

72%

71%

70%

2006

2003

2004

2005

2002

Hospital Carlos IIIARV failure
slide13

Resistance mutations at Hospital Carlos III

NRTI

NNRTI

PI

De Mendoza et al. ARHR 2007

slide14

Study population: 389 HIV patients who had failed PIs and begun PI/r regimens

Virological response defined as >1 log drop in HIV RNA at w24.

slide15

Resistance is not absolute

Susceptible

Resistant

De Mendoza et al. HIV Clin Trials 2006; 7: 163-71.

drug resistance interpretation
Drug Resistance Interpretation
  • Genotype
  • Phenotype
  • Drug Resistance algorithms:
    • Mutation list
    • Mutation score for especific drugs based on clinical response
    • Rega, ANRS, Stanford, geno2pheno, Artificial Neural Networks (ANN), etc.
cosas nuevas en 2007
Cosas Nuevas en 2007
  • Listado de mutaciones que deben aparecer en los informes de resistencias
  • Recomendaciones sobre cuando hacer resistencias
  • Hipersusceptibilidad
  • Resistencias a nuevos fármacos: RAL, ETV, Maraviroc
  • Polimorfismos frecuentes en subtipos no-B
  • Ponderación de cada mutación para cada fármaco
m todos utilizados en la elaboraci n de las gu as del 2007
Métodos utilizados en la elaboración de las guías del 2007
  • Listado de mutaciones de la IAS-USA 2007
  • Stanford University HIV drug resistance database
  • Celera: PRS for ViroSeq HIV-1 Genotyping software v2.8
  • Trugene guideline v.12
  • Prevalencia y asociación de mutaciones de resistencia en el fracaso.
  • Datos de los ensayos clínicos DUET, BENCHMRK y MOTIVATE
slide30

Agradecimientos

  • Grupo de Español de estudio de SCV y Plataforma de Resistencias del RIS:
  • - Jorge del Romero y Carmen Rodríguez. Centro Sanitario Sandoval, Madrid
  • Pilar Leiva. Hospital General de Asturias, Oviedo
  • Antonio Aguilera. Hospital Xeral de Santiago
  • Jose Pedreira. Hospital Juan Canalejo, La Coruña
  • Jesús Aguero, Ana Saiz. Hospital Marques de Valdecilla, Santander
  • José Mª Eiros, Raúl Ortíz de Lejarazu. Hospital Clínico de Valladolid
  • Federico Garcia. Hospital Clínico San Cecilio, Granada
  • Isabel Viciana. Hospital Virgen de la Victoria, Málaga
  • Manolo Leal, Alex Vallejo. Hospital Virgen del Rocio, Sevilla.
  • Javier Colomina. Hospital de la Ribera, Valencia
  • Concha Tuset. Hospital General de Valencia
  • Javier Martínez-Picado, Josep Mª Llibre, Bonaventura Clotet. Hospital Germans Trias i Pujol, Badalona
  • José Luis Blanco, Josep Mª Gatell. Hospital Clinic, Barcelona.
  • Melchor Riera, Carmen Vidal. Hospital Son Dureta, Palma de Mallorca.
  • Francesc Vidal. Hospital Joan XXIII, Tarragona
  • Estrella Caballero, Esteban Ribera. Hospital Vall d’ Hebrón, Barcelona.
  • Mª Jesús Pérez-Elias, Carolina Gutierrez, Santiago Moreno. Hospital Ramón y Cajal, Madrid.
  • Juan Luis Gómez-Sirvent. Hospital
  • Felix Gutierrez. Hospital de Elche, Elche
  • Rafael Benito. Hospital Lozano Blesa, Zaragoza
  • Julián Torre-Cisneros. Hospital Reina Sofia. Córdoba.
  • Hospital Carlos III:
  • Sección de Laboratorio:
  • Angélica Corral
  • Natalia Zahonero
  • Carolina Garrido
  • Eva Poveda
  • Sección Clínica:
  • Pablo Labarga
  • Pilar García Gasco
  • Pablo Barreiro
  • Vicente Soriano
  • Juan González-Lahoz