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XX Aos Tratando el VIH 1986-2006 Josep Mallolas Servei dInfeccions Hospital Clnic Slide 2 Slide 3 Slide 4 Slide 5 Slide 6 Slide 7 Slide 8 Slide 9 Slide 10 Slide 11 Slide 12 Slide 13 Slide 14 Slide 15 Slide 16 Slide 17 Slide 18 Slide 19 Slide 20 Slide 21 Slide 22 Slide 23 Slide 24 Slide 25 Slide 26 Slide 27 Slide 28 Slide 29 Slide 30 Slide 31 Slide 32 Slide 33 Slide 34 Slide 35 Slide 36 Slide 37 Slide 38 Slide 39 Slide 40 Slide 41 Slide 42 Slide 43 Slide 44 Slide 45 Slide 46 Slide 47 Slide 48 Slide 49 Slide 50 Slide 51 Slide 52 FROM BENCH TO CLINIC: Optimizing HIV Clinical Management MILESTONES IN THE MANAGEMENT OF HIV DISEASE 1. 1982-87: No ART 2. 1987-97: Suboptimal NRTI ART 3. 1997-02: Toxic HAART (cART) 4. 2002-05: 2nd generation cART 5. THE FUTURE..... Slide 53 FROM BENCH TO CLINIC: Optimizing HIV Clinical Management 1. 1982-87: No ART Learning from natural history Prophylaxis of opportunistic infections Slide 54 FROM BENCH TO CLINIC: Optimizing HIV Clinical Management 2. 1987-97: Suboptimal ART (NRTI) Proof of concept of ART Small, but not negligible impact on mortality Acummulation of resitance Accumulation of mytochrondrial toxicity Black decade or middle age of ART Slide 55 Slide 56 Mortalidad asociada al VIH-1. Tesis Doctoral. JB Prez-Cuevas. Tesis Doctoral. JB Prez-Cuevas. Hospital Clnic, Barcelona. HAART Slide 57 FROM BENCH TO CLINIC: Optimizing HIV Clinical Management 3. 1997-02: Toxic HAART (cART) New families (PI, NNRTI) and cART Big impact on VL, CD4, OI, mortality Metabolic disturbances and lipodystrophy Adherence problems Accumulation and transmission of resistance Desire of STI Slide 58 AIDS prevalence *Adjusted for reporting delays United States, 1985-1999* HAART introduced Number of mortalities 0 5,000 10,000 15,000 20,000 25,000 Mortalities AIDS Prevalence 0 150,000 100,000 50,000 200,000 250,000 300,000 350,000 198519861987198819891990199119921993199419951996199719981999 Quarter-Year Impact of HAART on HIV-related mortality Slide 59 Slide 60 Slide 61 Slide 62 Slide 63 Slide 64 0.00001 0.0001 0.001 0.01 0.1 1 10 100 1000 10000 012 3 45678 Time on HAART (years) Frequency (IUPM) Frequency of Latently Infected CD4+ T Cells as a Function of Time on HAART t = 44.2 months 73.4 years Slide 65 Slide 66 Slide 67 Slide 68 Slide 69 Slide 70 Slide 71 Slide 72 Slide 73 Slide 74 Slide 75 Structured Therapy Interuption1998-2003R.I.P. Slide 76 FROM BENCH TO CLINIC: Optimizing HIV Clinical Management 4. 2002-05: 2nd generation cART Optimized NRTI (less toxic) Optimized PI (lipid friendly, ritonavir boosted) Proof of concept: fusion inhibitors CCR5 inhibitors integrase inhibitors cART feasible in developing world Slide 77 FROM BENCH TO CLINIC: Optimizing HIV Clinical Management 4. 2002-05: 2nd generation cART High, durable & clean response in ART naive patients Unprecedented response rate in salvage therapy Better prospects in resistance accumulation Better prospects in lipodystrophy Slide 78 Slide 79 Slide 80 FROM BENCH TO CLINIC: Optimizing HIV Clinical Management 5. THE FUTURE..... - Strategic studies - Revisiting the concept of eradication - Revisiting the concept of cART for a limited period of time: Immunotherapy /Therapeutic vaccines - Late arrivals. Old OI - Access to cART - Prevention of HIV infection Slide 81 Slide 82 Slide 83 Slide 84 Slide 85 Slide 86 Ciclo del VIH-1 NRTI NtRTI NNRTI NRTI NtRTI NNRTI PI Inhibidores Entrada Inhibidores Entrada Inhibidores Integrasa Inhibidores Integrasa Slide 87 Slide 88 Slide 89 Slide 90 Baseline patients characteristics n = 16 Median Age 45 Male Sex85% AIDS criteria 77% Median CD4 cell count186 Median plasma HIV RNA(log)4,99 Median previous ARVT9 Median number of RT/TAMs6/4 Median number of PRT/UPAMs11/3 Previous T-20 Rx31% VL < 200 anytime31% Slide 91 Virological follow-up: N: 1312 108 5 VL>2log:9/12 VL>1log:11/12 VL>2log:9/10 VL>2log:7/8 Slide 92 Slide 93 Slide 94 Thirty-six years ago, President Kennedygave us a goal of reaching the moon, and we achieved it - ahead of time Let us today set a new national goal for science in the age of biology. Today, let us commit ourselves to developing an AIDS vaccine within the next decade - President Bill Clinton, 1997 HIV-1 Vaccines Slide 95 Slide 96 AIDS today: year 2006 AIDS is a STD and a world wide epidemy (sub-Saharan Africa, Southeast Asia, America). Is threatening global economical & demographical development and security Slide 97 Slide 98 Slide 99 Slide 100