1 First cases of unusual immune deficiency are identified among gay men in USA, and a new deadly disease noticed
45
2 Acquired Immune Deficiency Syndrome (AIDS) is defined for the first time
40
3 The Human Immune Deficiency Virus (HIV) is identified as the cause of AIDS
35
4 In Africa, a heterosexual AIDS epidemic is revealed 5 The first HIV antibody test becomes available 6 Global Network of People living with HIV/AIDS (GNP+) (then International Steering Committee of People Living with HIV/AIDS) founded 7 The World Health Organisation launches the Global Programme on AIDS
30 25 20
8 The first therapy for AIDS – zidovudine, or AZT -- is approved for use in the USA
15 10 5
1
2
3 4
6
5
9
15
16
14
10 Highly Active Antiretroviral Treatment launched 11 Scientists develop the first treatment regimen to reduce motherto-child transmission of HIV
13 11
10
9
In 1991-1993, HIV prevalence in young pregnant women in Uganda and in young men in Thailand begins to decrease, the first major downturns in the epidemic in developing countries
12
7 8
Children orphaned by AIDS in subsubSaharan Africa
12 UNAIDS is created 13 Brazil becomes the first developing country to provide antiretroviral therapy through its public health system 14 The UN General Assembly Special Session on HIV/AIDS. Global Fund to fight AIDS, Tuberculosis and Malaria launched 15 WHO and UNAIDS launch the "3 x 5" initiative with the goal of reaching 3 million people in developing world with ART by 2005 16 Global Coalition on Women and AIDS launched
0 1980
1985
1990
1995
Dpto. Farmacología. UAM.
2005
2000
www.unaids.org Regional HIV and AIDS statistics and features, 2003 and 2005 REGION
Sub-Saharan Africa North Africa and Middle East Asia Oceania Latin America Caribbean Eastern Europe and Central Asia North America, Western and Central Europe TOTAL
Adults (15+) and Adults (15+) and children children living with HIV newly infected with HIV 2003
2005
2003
Adult (15+) and child deaths due to AIDS
2005
2003
24.5 million
23.5 million
2.7 million
2.6 million
6.1
6.2
2.0 million
1.9 million
[21.6‒27.4 million]
[20.8‒26.3 million]
[2.3‒3.1 million]
[2.3‒3.0 million]
[5.4‒6.8]
[5.5‒7.0]
[1.7‒2.3 million]
[1.7‒2.3 million]
440 000
2005
Adult (15-49) prevalence (%)
380 000
64 000
54 000
[220 000‒620 000]
[38 000‒210 000
[31 000‒150 000
8.3 million
7.6 million
930 000
860 000
0.4
0.4
[5.7‒12.5 million]
[5.2‒11.3 million]
[620 000‒2.4 million]
[560 000‒2.3 million]
[0.3‒0.6]
[0.2‒0.6]
0.3
0.3
[4300-69 000]
[0.2‒0.8]
[0.2‒0.7]
[250 000‒720 000]
78 000
66 000
[48 000‒170 000]
[41 000‒140 000]
7200
[3500‒55 000]
9000
1.6 million
1.4 million
140 000
130 000
[1.2‒2.4 million]
[1.1‒2.0 million]
[100 000‒420 000]
[95 000‒310 000]
37 000
34 000
[26 000‒54 000]
[24 000‒47 000]
220 000
160 000
330 000 [240 000‒420 000]
1.5 million
310 000 [230 000‒400 000]
1.1 million
0.2
0.2
[0.1‒0.4]
[0.1‒0.3]
0.5
0.5
[0.4‒1.2]
[0.4‒0.7]
1.6
1.5
[1.1‒2.2]
[1.1‒2.0]
0.8
0.6 [0.4‒1.0]
2005
2003
37 000
34 000
[20 000‒62 000]
[18 000‒57 000]
600 000
500 000
[400 000‒850 000]
[340 000‒710 000]
3400
2300
[1900‒5500]
[1300‒3600]
59 000
51 000
[47 000‒76 000]
[40 000‒67 000]
27 000
28 000
[19 000‒36 000]
[19 000‒38 000]
53 000
28 000
[36 000‒75 000]
[19 000‒39 000]
[790 000‒1.7 million]
1.8 million
[150 000‒650 000]
[110 000‒440 000]
[0.6‒1.4]
2.0 million
0.5
0.5
[1.4‒2.9 million]
[1.3‒2.7 million]
[52 000‒98 000]
[52 000‒98 000]
[0.4‒0.7]
[0.3‒0.6]
38.6 million
36.2 million
4.1 million
3.9 million
1.0
1.0
2.8 million
2.6 million
[33.4‒46.0 million]
[31.4‒42.9 million]
[3.4‒6.2 million]
[3.3‒5.8 million]
[0.9‒1.2]
[0.8‒1.2]
[2.4‒3.3 million]
[2.2‒3.1 million]
[1.0‒2.3 million]
Dpto. Farmacología. UAM.
65 000
65 000
30 000
30 000
[24 000‒45 000]
[24 000‒45 000]
2.3
1
www.unaids.org A global view of HIV infection 38.6 million people [33.4‒46.0 million] living with HIV, 2005
Dpto. Farmacología. UAM.
2.4
www.unaids.org Estimated total annual resources available for AIDS, 1996‒ 1996‒2005 9000
Signing of Declaration of Commitment on HIV/AIDS
8000 7000
8297*
• International donors, domestic spending (including public spending and out-of-pocket expenditures)
US$ million
6000 5000
• International Foundations and Global Fund included from 2003 onwards, PEPFAR included from 2004 onwards
4000 3000 2000
* Projections based on previous pledges and commitments (range of the estimation: US$7.5 to US$8.5 billion).
1623 1000
Data include:
292
0 1996
1997
1998 1999 2000
Dpto. Farmacología. UAM.
2001 2002
2003
2004
2005
3.8
Ciclo de replicación del VIH
Dpto. Farmacología. UAM.
Goodman-Gilman 9th edition
2
ANTI-RETROVIRALES
u Inhibidores de la Transcriptasa Inversa. u Nucleósidos. u No Nucleósidos.
u Inhibidores de Proteasas. u Inhibidores de proteínas de Fusión.
Dpto. Farmacología. UAM.
ANTI-RETROVIRALES Inhibidores de la Transcriptasa Inversa ®Análogos
ANTI-RETROVIRALES Inhibidores de la Transcriptasa Inversa ►Análogos Nucleósidos la Transcriptasa Inversa, actuando como falsos Nucleótidos. ►Impiden la Infección de nuevas células. ►Farmacocinética ►Inhiben
►Aceptable ►Escasa
Biodisponibilidad Oral. penetración en LCR (excepto AZT). Renal
►Eliminación
►Rápido
desarrollo de Resistencias Virales
►Tratamiento
Combinado.
►Toxicidad ►Mielotóxicos
(AZT). Anemia, Trombopenia. y Pancreatotóxicos (DDI, DDC). ►Meurotóxicos y Mielotóxicos (D4T). ►Neurotóxicos
Dpto. Farmacología. UAM.
3
Nucleósidos Anti-Retrovirales. Farmacocinética Parámetro Biodisponibilidad (%) AUC- Ingesta (%) T1/2 Plasm.(h) T1/2 Cel. (h) Ratio CSF/Plasma Unión Prot.(%) Metabolismo