1. XX Años Tratando el VIH 1986-2006 Josep Mallolas Servei d´Infeccions Hospital Clínic

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.....

53. FROM BENCH TO CLINIC: Optimizing HIV Clinical Management 1. 1982-87: No ART Learning from natural history Prophylaxis of opportunistic infections

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

56. Mortalidad asociada al VIH-1. Tesis Doctoral. JB Pérez-Cuevas. Tesis Doctoral. JB Pérez-Cuevas. Hospital Clínic, Barcelona. HAART

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

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

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 ½ = 44.2 months 73.4 years

75. Structured Therapy Interuption1998-2003R.I.P.

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

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

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

86. Ciclo del VIH-1 NRTI NtRTI NNRTI NRTI NtRTI NNRTI PI Inhibidores Entrada Inhibidores Entrada Inhibidores Integrasa Inhibidores Integrasa

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%

91. Virological follow-up: N: 1312 108 5 ↓VL>2log:9/12 ↓VL>1log:11/12 ↓VL>2log:9/10 ↓VL>2log:7/8

94. Thirty-six years ago, President Kennedy…gave 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

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