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XX Años Tratando el VIH 1986-2006 Josep
Mallolas Servei dInfeccions Hospital Clínic
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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 .....
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1. 1982-87 No ART Learning from natural
history Prophylaxis of opportunistic infections
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2. 1987-97 Suboptimal ART (NRTI) Proof of
concept of ART Small, but not negligible impact
on mortality Acummulation of resitance Accumulati
on of mytochrondrial toxicity Black decade or
middle age of ART
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Mortalidad asociada al VIH-1.
HAART
Tesis Doctoral. JB Pérez-Cuevas. Hospital Clínic,
Barcelona.
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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
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Impact of HAART on HIV-related mortality
United States, 1985-1999
25,000
350,000
Mortalities
AIDS Prevalence
300,000
20,000
HAART introduced
250,000
15,000
200,000
AIDS prevalence
Number of mortalities
150,000
10,000
100,000
5,000
50,000
0
0
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
Quarter-Year
Adjusted for reporting delays
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Frequency of Latently Infected CD4 T Cells as a
Function of Time on HAART
10000
1000
100
10
Frequency (IUPM)
1
0.1
0.01
0.001
0.0001
0.00001
0
1
2
3
4
5
6
7
8
Time on HAART (years)
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Structured Therapy Interuption 1998-2003 R.I.P.
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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
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4. 2002-05 2nd generation cART High, durable
clean response in ART naive patients Unprecedente
d response rate in salvage therapy Better
prospects in resistance accumulation Better
prospects in lipodystrophy
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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
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Ciclo del VIH-1
Inhibidores Entrada
PI
NRTI NtRTI NNRTI
Inhibidores Integrasa
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Baseline patients characteristics
n 16 Median Age 45 Male
Sex 85 AIDS criteria 77 Median CD4 cell
count 186 Median plasma HIV RNA(log) 4,99 Medi
an previous ARVT 9 Median number of
RT/TAMs 6/4 Median number of PRT/UPAMs 11/3 Pre
vious T-20 Rx 31 VL lt 200 anytime 31
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Virological follow-up
?VLgt2log9/10
?VLgt2log9/12 ?VLgt1log11/12
?VLgt2log7/8
N 13 12 10 8 5
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HIV-1 Vaccines
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
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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
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