Hartmut Stocker Vivantes-Auguste Viktoria Klinikum; HID 2008

Transkript

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2 ART ein Kinderspiel

3 Womit soll man bloß anfangen?

4 ... mit der besten Kombi

5 Die beste Kombi (Stand 2008) Kaletra Telzir Invirase Reyataz Crixivan Viracept Retrovir Zerit Epivir Emtriva Videx Hivid Viread Ziagen Combivir Kivexa Truvada Sustiva Viramune Rescriptor

6 Die besten NRTI (1999 bis 2006)

7 Combivir vs. Videx/Zerit ALBI Molina, et al., J Infect Dis, 1999, 180 Combivir vs. Videx/Epivir Combivir vs. Kivexa Zerit/Epivir vs. Viread/Epivir NN CNA Combivir vs. Truvada 934 Maggiolo, et al., Antivir Ther, 2003, 8 DeJesus, et al., Clin Infect Dis, 2004, 39 Gallant, et al., Jama, 2004, 292 Gallant, et al., N Engl J Med, 2006, 354 Pozniak, et al., J Acquir Immune Defic Syndr, 2006, 43 Arribas, et al., J Acquir Immune Defic Syndr, 2008, 47

8 NRTI (Ergebnisse der Vorrunde) Videx, Zerit, Hivid sind raus Combivir wird geduldet Truvada und......kivexa streiten um den Sieg P. Sax, P., C. Tierney, A. Collier, M. Fischl, C. Godfrey, N. Jahed, K. Droll, L. Peeples, L. Myers, G. Thal, J. Rooney, B. Ha, W. Woodward, and E. Daar Presented at the 17th Int AIDS Conf, Mexico City, Mexico, Aug 3-8. Smith, K. Y., D. M. Fine, P. Patel, N. C. Bellos, L. Sloan, P. Lackey, P. N. Kumar, D. H. Sutherland-Phillips, C. Vavro, L. Yau, and M. S. Shaefer Presented at the 17th Int AIDS Conf, Mexico City, Mexico

9 Der beste Protease Hemmer

10 Womit fangen wir an? CASTLE: Kaletra vs. Reyataz Molina, J. M., J. Andrade-Villanueva, J. Echevarria, P. Chetchotisakd, J. Corral, N. David, G. Moyle, M. Mancini, L. Percival, R. Yang, A. Thiry, and D. McGrath Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet 372: KLEAN: GEMINI: Kaletra vs. Telzir Kaletra vs. Invirase Eron, J., Jr., P. Yeni, J. Gathe, Jr., V. Estrada, E. DeJesus, S. Staszewski, P. Lackey, C. Katlama, B. Young, L. Yau, D. Sutherland- Phillips, P. Wannamaker, C. Vavro, L. Patel, J. Yeo, and M. Shaefer The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial. Lancet 368: Walmsley S, Ruxrungtham K, Slim J, Ward D, Larson P, Raffi FL. Saquinavir/r (SQV/r) BID versus lopinavir/r (LPV/r) BID, plus emtricitabine/tenofovir (FTC/TDF) QD as initial therapy in HIV-1 infected patients: the GEMINI Study. 11th European AIDS Conference. Madrid, Spain; 2007

11 Protease Hemmer Crixivan und Viracept sind raus Kaletra = Reyataz = Invirase = Telzir Es sind die Nebenwirkungen... Es ist der Comfort...

12 Der beste NNRTI

13 2NN: Sustiva vs. Viramune van Leth, F., P. Phanuphak, K. Ruxrungtham, E. Baraldi, S. Miller, B. Gazzard, P. Cahn, U. G. Lalloo, I. P. van der Westhuizen, D. R. Malan, M. A. Johnson, B. R. Santos, F. Mulcahy, R. Wood, G. C. Levi, G. Reboredo, K. Squires, I. Cassetti, D. Petit, F. Raffi, C. Katlama, R. L. Murphy, A. Horban, J. P. Dam, E. Hassink, R. van Leeuwen, P. Robinson, F. W. Wit, and J. M. Lange Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 363:

14 NNRTI Rescriptor ist raus Sustiva und Viramune sind (fast) gleich gut Es sind die Nebenwirkungen...

15 Kaletra gegen Sustiva VL < 50/ml nach 96 Wochen Riddler, S. A., R. Haubrich, G. DiRienzo, L. Peeples, W. G. Powderly, K. L. Klingman, K. W. Garren, T. George, J. F. Rooney, B. Brizz, D. Havlir, J. W. Mellors, and A. C. T. G. S. Team Presented at the 16th Int Conf AIDS, Toronto, Canada, Aug VL < 50/ml [%] LPV/r + NRTI EFV + NRTI

16 Und noch während die Gewinner feiern...

17 Womit fangen wir an? CASTLE: Kaletra vs. Reyataz Molina, J. M., J. Andrade-Villanueva, J. Echevarria, P. Chetchotisakd, J. Corral, N. David, G. Moyle, M. Mancini, L. Percival, R. Yang, A. Thiry, and D. McGrath Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet 372: KLEAN: GEMINI: ARTEMIS: Kaletra vs. Telzir Kaletra vs. Invirase Kaletra vs. Prezista Eron, J., Jr., P. Yeni, J. Gathe, Jr., V. Estrada, E. DeJesus, S. Staszewski, P. Lackey, C. Katlama, B. Young, L. Yau, D. Sutherland- Phillips, P. Wannamaker, C. Vavro, L. Patel, J. Yeo, and M. Shaefer The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial. Lancet 368: Walmsley S, Ruxrungtham K, Slim J, Ward D, Larson P, Raffi FL. Saquinavir/r (SQV/r) BID versus lopinavir/r (LPV/r) BID, plus emtricitabine/tenofovir (FTC/TDF) QD as initial therapy in HIV-1 infected patients: the GEMINI Study. 11th European AIDS Conference. Madrid, Spain; 2007 Ortiz, R., E. Dejesus, H. Khanlou, E. Voronin, J. van Lunzen, J. Andrade-Villanueva, J. Fourie, S. De Meyer, M. De Pauw, E. Lefebvre, T. Vangeneugden, and S. Spinosa-Guzman Efficacy and safety of oncedaily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1- infected patients at week 48. Aids 22:

18 2NN: Sustiva vs. Viramune 004: Sustiva vs. Isentress van Leth, F., P. Phanuphak, K. Ruxrungtham, E. Baraldi, S. Miller, B. Gazzard, P. Cahn, U. G. Lalloo, I. P. van der Westhuizen, D. R. Malan, M. A. Johnson, B. R. Santos, F. Mulcahy, R. Wood, G. C. Levi, G. Reboredo, K. Squires, I. Cassetti, D. Petit, F. Raffi, C. Katlama, R. L. Murphy, A. Horban, J. P. Dam, E. Hassink, R. van Leeuwen, P. Robinson, F. W. Wit, and J. M. Lange Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 363: Markowitz, M., B. Y. Nguyen, E. Gotuzzo, F. Mendo, W. Ratanasuwan, C. Kovacs, G. Prada, J. O. Morales-Ramirez, C. S. Crumpacker, R. D. Isaacs, L. R. Gilde, H. Wan, M. D. Miller, L. A. Wenning, and H. Teppler Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV- 1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr 46: Murray, J. M., S. Emery, A. D. Kelleher, M. Law, J. Chen, D. J. Hazuda, B. Y. Nguyen, H. Teppler, and D. A. Cooper Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. Aids 21:

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20 Wohin geht die Forschung? Aus der Vergangenheit lernen... Viele virologisch gute Medikamente sind gestorben Ein Medikament hemmt nicht nur das Virus Nebenwirkungen Resistenzprofil und Folgeoptionen Kombinierbarkeit Mahlzeiten Tablettengröße und Geruch etc.

21 Welche Fragen ergeben sich Ist das NRTI + PI/NNRTI Konzept noch richtig? Müssen es unbedingt drei Medikamente sein? Muss es unbedingt jeden Tag sein Können wir das Virus vielleicht doch eradizieren?

22 Vielen Dank Hartmut Stocker Vivantes-Auguste Viktoria Klinikum

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