Jose Moltó Marhuenda *

Autor invitado por SIIC

El trabajo contribuye a optimizar la dosis de darunavir a utilizar en el tratamiento de rescate de pacientes infectados por el VIH previamente tratados con otros inhibidores de la proteasa.

COCIENTE INHIBITORIO DE DARUNAVIR EN EL TRATAMIENTO DE RESCATE

El objetivo de este estudio fue evaluar la relación entre la respuesta virológica y el cociente inhibitorio de Darunavir en 37 pacientes que iniciaban un tratamiento de rescate basado en Darunavir. El cociente inhibitorio virtual (vIQ) predijo la respuesta virológica mejor que las concentraciones de Darunavir o el número de mutaciones de resistencia por separado. Los pacientes con un vIQ ≥12.5 tenían una probabilidad 5 veces mayor de conseguir una carga viral <50 copias/ml tras 48 semanas de seguimiento.

*Jose Moltó Marhuenda
describe para SIIC los aspectos relevantes de su trabajo
DARUNAVIR INHIBITORY QUOTIENT PREDICTS THE 48-WEEK VIROLOGICAL RESPONSE TO DARUNAVIR-BASED SALVAGE THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PROTEASE INHIBITOR-EXPERIENCED PATIENTS
Institución principal de la investigación
*Hospital Universitari Germans Trias I Pujol, Barcelona, España
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Referencias bibliográficas
1. Barrios AAL, Rendón O, Gallego L, Martín Carbonero L, Valer P, Ríos I, Maida T, García Benayas I, Jiménez Nacher J, González Lahoz, Soriano V. Predictors of virological response to atazanavir in protease inhibitor-experienced patients. HIV Clin Trials 5:201-5, 2004.
2. Bartlett JGH, Clifford L, and the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antirretroviral agents in HIV-1-infected adults and adolescents. Available at:http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf. Last accessed March 2008.
3. Cahn PJ, Villacian C, Katlama B, Grinsztejn K, Arasteh P, López N, Clumeck J, Gerstoft N, Stavrineas S, Moreno F, Antunes D, Neubacher S, Mayers D. Ritonavir-boosted tipranavir demonstrates superior efficacy to ritonavir-boosted protease inhibitors in treatment-experienced HIV-infected patients: 24 week results of the resist-2 trial. Clin Infect Dis 43:1347-1356, 2006.
4. Clotet B, Bellos N, Molina JM, Cooper D, Goffard JC, Lazzarin A, Wöhrmann A, Katlama C, Wilkin T, Haubrich R, Cohen C, Farthing C, Jayaweera D, Markowitz M, Ruane P, Spinosa-Guzman S, Lefebvre E, and the POWER 1 and 2 study groups. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomized trials. Lancet 369:1169-1178, 2007.
5. D'Avolio A, Siccardi M, Sciandra M, Lorena B, Bonora S, Trentini L, Di Perri G. HPLC-MS method for the simultaneous quantification of the new HIV protease inhibitor darunavir, and 11 other antiretroviral agents in plasma of HIV-infected patients. Journal of Chromatography B 859:234-240, 2007.
6. De Meyer S, Azijn H, Surleraux D, Jochmans D, Thari A, Pawels R, Wiquerinck P, De Bethune MP. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother 49:2314-2321, 2005.
7. De Meyer S, Vangeneugden T, Lefebvre E, Van Mack H, Azjin H, De Baere I, Van Baelen B, De Béthume MP. Phenotypic and genotypic determinants of TMC114 (darunavir) resistance: POWER 1, 2, and 3 pooled analysis. 8th International Congress on Drug Therapy in HIV Infection. Abstract 196, 2006.
8. Gathe J, Cooper DA, Farthing C, Jayaweera D, Norris D, Pierone G, Steinhart CR, Trottier B, Walmsley SL, Workman C, Mukwaya G, Kohlbrenner V, Dohnanyi C, McCallister S, Mayers D, and the RESIST-1 Study Group. Efficacy of the protease inhibitor tipranavir plus ritonavir in treatment-experienced patients: 24 week analysis from the RESIST-1 trial. Clin Infect Dis 43:1337-1346, 2006.
9. Gathe J, De Jesus E, Falcon R, Vangeneugden T. Examination of factors influencing response to darunavir combined with low-dose ritonavir in POWER 1, 2 and 3: Pooled 48-week analysis. Frontiers in Drug Development for Antiretroviral Therapies. Abstract 66, 2006.
10. Gonzalez de Requena D, Bonora S, Calcagno S, D'Avolio A, Siccardi M, Fontana S, Milia MG, Sciandra M, Garazzino S, Di Garbo A, Baietto L, Trentini L, Di Perri G. Tipranavir (TPV) genotypic inhibitory quotient predicts virological response at 48 weeks to TPV-based salvage regimens. Antimicrob Agents Chemother 52:1066-1071, 2008.
11. Hoefnagel JGM, Koopmans PP, Burger DM, Schuurman R, Galama JMD. Role of the inhibitory quotient in HIV therapy. Antivir Ther 10:879-892, 2005.
12. Johnson VA, Brun-Vezinet F, Clotet B, Günthard HF, Kuritzkes DR, Pillay D, Schapiro JM, Richman DD. Update on the drug resistance mutations in HIV-1: 2007. Topics HIV Med 15:119-125, 2007.
13. Lazzarin A, Campbell T, Clotet B, Johnson M, Katlama C, Moll A, Towner W, Trottier B, Peeters M, Vingerhoets J, De Smedt G, Baeten B, Beets G, Sinha R, Woodfall B, and the DUET-2 study group. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1 infected patients in DUET-2: 24-week results from a randomized, double-blind, placebo-controlled trial. Lancet 370:39-48, 2007.
14. Marcelin AG, Cohen-Codar I, King MS, Colson P, Guillevic E, Descamps D, Lamotte C, Schneider V, Ritter J, Segondy M, Peigue-Lafeuille H, Morand-Joubert L, Schmuck A, Ruffault A, Palmer P, Chaix ML, Mackiewicz V, Brodard B, Izopet J, Cottalorda J, Kohli E, Chauvin JP, Kempf DJ, Peytavin G, Calvez V. Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients. Antimicrob Agents Chemother 49:1720-1726, 2005.
15. Marcelin AG, Dalban C, Peytavin G, Lamotte C, Agher R, Delaugerre C, Wirden M, Conan F, Dantin S, Katlama C, Costagliola D, Calvez V. Clinically relevant interpretation of genotype and relationship to plasma drug concentrations for resistance to saquinavir-ritonavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients. Antimicrob Agents Chemother 48:4687-4692, 2004.
16. Marcelin AG, Lamotte C, Delaugerre C, Ktorza N, Mohand HA, Cacace R, Bonmarchand M, Wirden M, Simon A, Bossi P, Bricaire F, Costagliola D, Katlama C, Peytavin G, Calvez V, and the Genophar Study Group. Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients. Antimicrob Agents Chemother 47:594-600, 2003.
17. Molina JM, Cohen C, Katlama C, Grinsztejn B, Timerman A, Pedro RJ, Vangeneugden T, Miralles D, De Meyer S, Parys W, Lefebvre E, and the TMC114-C208 and -C215 Study Groups. Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients. 24-week results of POWER 3. J Acquir Defic Syndr 46:24:31, 2007.
18. Nelson M, Arastéh K, Clotet B, Cooper DA, Henry K, Katlama C, Lalezari JP, Lazzarin A, Montaner JSG, O'Hearn M, Piliero PJ, Reynes J, Trottier B, Walmsley SL, Cohen C, Eron JJ, Kuritzkes DR, Lange J, Stellbrink HJ, Delfraissy JF, Buss NE, Donatacci L, Wat C, Smiley L, Wilkinson M, Valentine A, Guimaraes D, DeMasi R, Chung J, Salgo MP. Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials. J Acquir Immune Defic Syndr 40:404-412, 2007.
19. Parkin N, Stawiski E, Chappey C, Coakley E. Darunavir-amprenavir cross-resistance in clinical simples submitted for phenotype-genotype combination resistance testing. 14th Conference on Retroviruses and Opportunistic Infections. Abstract 607, 2007.
20. Sekar V, De Meyer S, Vangeneugden T, Lefebvre E, De Pauw M, Van Baelen B, De Paepe E, De Béthune MP, Hoetelmans R, Parys W. Pharmacokinetic/pharpacodynamic (PK/PD) analyses of TMC114 in the POWER 1 and POWER 2 trials in treatment-experienced HIV-infected patients. 13th Conference on Retroviruses and Opportunistic Infections. Abstract J121, 2006.
21. Sekar V, De Meyer S, Vangeneugden T, Lefebvre E, De Pauw M, Van Baelen B, De Paepe E, De Béthune MP, Miralles D, Hoetelmans R. Absence of TMC114 exposure-efficacy and exposure-safety relationships in POWER 3. 16th International AIDS Conference. Abstract TUPE0078, 2006.
22. Valdez Madruga J, Cahn P, Grinsztejn B, Haubrich R, Lalezari J, Mills A, Pialoux G, Wilkin T, Peeters M, Vingerhoets J, De Smedt G, Leopold L, Trefiglio R, Woodfall B, and DUET-1 study group. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1 infected patients in DUET-1: 24-week results from a randomized, double-blind, placebo-controlled trial. Lancet 370:29-38, 2007.

Otros artículos de Jose Moltó Marhuenda

Moltó J, Valle M, Santos JR, Mothe B, Miranda C, Cedeño S, Negredo E, Yritia M, Videla S, Barbanoj MB, Clotet B. Pilot study assessing treatment simplification to darunavir/ritonavir 900/100 mg once daily guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients. Antivir Ther 15:219-225, 2010.
Moltó J, Valle M, Santos JR, Miranda C, Cedeño S, Negredo E, Yritia M, Videla S, Clotet B. Efficacy and safety of ritonavir dose reduction based on the tipranavir inhibitory quotient in HIV-infected patients on salvage antiretroviral therapy with tipranavir/ritonavir. AIDS Research and Human Retroviruses 26:1191-6, 2010.
Moltó J, Valle M, Ferrer E, Domingo P, Curran A, Santos JR, Mateo MG, Di Yacovo MS, Miranda C, Podzamczer D, Clotet B; on behalf of the DRV600 Study Group. Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically uppressed HIV-infected patients: a randomized clinical trial. J Antimicrob Chemother 70(4):1139-45, 2015.

Para comunicarse con Jose Moltó Marhuenda mencionar a SIIC como referencia:
jmolto@flsida.org

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Acerca del trabajo completo

COCIENTE INHIBITORIO DE DARUNAVIR EN EL TRATAMIENTO DE RESCATE

Título original en castellano
EL COCIENTE INHIBITORIO PREDICE LA RESPUESTA VIROLOGICA A 48 SEMANAS DEL TRATAMIENTO DE RESCATE BASADO EN DARUNAVIR EN PACIENTES INFECTADOS POR EL VIRUS DE INMUNODEFICIENCIA HUMANA PREVIAMENTE TRATADOS CON INHIBIDORES DE LA PROTEASA.

Autores
Jose Moltó Marhuenda¹, José Ramon Santos², Núria Perez Alvarez³, Cristina Miranda Sánchez⁴
1 Médico, Hospital Universitari Germans Trias I Pujol, Barcelona, España, Physician
2 Médico, Fundació Lluita Contra la Sida, Consultant
3 Estadistica, Fundació Lluita Contra la Sida, Estadistica
4 Nurse, Fundació Lluita Contra la Sida, Nurse

Acceso a la fuente original
Antimicrobial Agents and Chemotherapy
http://aac.asm.org/

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