FARMACI, INNOVAZIONE e INFEZIONE DA HIV / AIDS

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1 FARMACI, INNOVAZIONE e INFEZIONE DA HIV / AIDS Stefano Vella Dipartimento del Farmaco Istituto Superiore di Sanità - Roma

2 Stages of HIV-1 Life Cycle Targeted by Anti-HIV Drugs In: Gulick RM, Topics HIV Med, 2002;10(4). The International AIDS Society USA

3 Concorde Trial

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9 Stages of HIV-1 Life Cycle Targeted by Anti-HIV Drugs In: Gulick RM, Topics HIV Med, 2002;10(4). The International AIDS Society USA

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11 Deaths per 100,000 Population Trends in Annual Rates of Death from Leading Causes of Death Among Persons Years Old, USA, Unintentional injury Cancer Heart disease Suicide 15 HIV infection 10 Homicide National Center for Health Statistics National Vital Statistics System 90 Year * *Preliminary 1998 data Chronic liver disease Stroke Diabetes

12 Mortality vs. HAART Utilization Deaths per 100 Person-Years USE OF HAART dpercentage ays on HA RT 25 of Patient DEATHS YDeaths ears per 100 Person Palella F et al, HOPS Study Percentage of Patient Days on HAART 35

13 APRIL2.jpg

14 I nuovi farmaci

15 HIV Attachment and Fusion Targets for Inhibition CD4 Binding CD4 binding inhibitors Co-receptor Binding gp41 Virus-Cell Fusion CCR5 antagonists Fusion inhibitors gp120 V3 loop CD4 Cell Membrane CCR5/CXCR4 (R5/X4) Adapted from Moore JP, et al. Proc Natl Acad Sci U S A. 2003;100:

16 From MR Furtado et al., N Engl J Med 340: , 1999.

17 Mutations associated with diketo acid and L-870,810 resistance map to distinct regions of the integrase active site

18 Drugs Available for HIV Therapy (2006) NRTI NNRTI PI - Zidovudine (AZT) - Efavirenz (EFV) - Stavudine (D4T) - Nevirapine (NVP) - Lamivudine (3TC) - Didanosine (ddl) - Abacavir (ABC) - Zalcitabine (ddc) - Emtricitabine (FTC) NtRTI FUSION Inhib. - Indinavir (IDV) - Enfuvirtide(ENF) - Nelfinavir (NFV) - Saquinavir (SQV) - Amprenavir (APV) - Ritonavir (RTV) - Lopinavir (LPV/r) - Atazanavir (ATV) - Tipranavir (TPV) + 4 fixed combinations: Abacavir/3TC Tenofovir/FTC Zidovudine/3TC - Tenofovir (TDF) Tenofovir/FTC/Efavirenz (US 1 QD)

19 Trends in Maternal Antiretroviral Therapy and Perinatal HIV Transmission, Women and Infants Transmission Study: No ART HAART 60 Monotherapy % % 19.4% % MultiART 9.0% % % % 3.0% 2.1% Year of Enrollment % 1.4% 1.6% % % Receiving Therapy Transmission Rate per

20 L altra innovazione: l accesso alle terapie nel Sud del Mondo

21 A Global View of HIV Infection Adult prevalence rate Prevalence 15.0% 36.0% 5.0% 15.0% 1.0% 5.0% 0.5% 1.0% 0.1% 0.5% 0.0% 0.1% not available

22 Leading causes of death in Africa % of Total HIV/AIDS Malaria Lower respiratory infections Perinatal conditions Diarrhoeal disease Source: The World Health Report 2001, WHO Tuber culosis Measles Cerebro vascular disease Ischaemic Heart disease Maternal conditions

23 Life Expectancy in Different African Countries Life expectancy at birth, in years Botswana Uganda South-Africa 55 Zambia 50 Zimbabwe Source: United Nations Population Division, 1998

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26 Durban 2000 Activism from the South Global March for access to HIV treatment Treatment Access Campaign (and others) EVERYONE HAS THE RIGHT TO HEALTH! All people with HIV/AIDS have a right to access treatments in addition to health care, employment, education, clean water, adequate nutrition, and housing. Denying people with HIV/AIDS access to affordable medicines in order to protect profits or intellectual property rights, is tantamount to genocide.

27 2001 Global Commitment Kofi Annan, UN Secretary General: Call for 7 10 billion war chest against AIDS and the creation of the Global Fund (launched Jan 2002) we must put care and treatment within everyone's reach. UNGASS AIDS, June 2001 Declaration of Commitment: make every effort to provide the highest attainable standard of treatment for HIV/AIDS, including the effective use of qualitycontrolled anti-retroviral therapy Schwartländer et al, Science, June 2001

28 Massive reduction in price too little too late? Generic companies start to Companies agree to the produce ARVs principle of differential pricing

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31 People on ARV therapy in developing countries Thousands North Africa and the Middle East Europe and Central Asia East, South and South - East Asia Latin America and the Caribbean Sub - Saharan Africa end mid- end mid- end mid- end

32 L accesso ai farmaci e alle cure essenziali per i milioni che vivono nel sud del mondo rappresenta una delle sfide più affascinanti della medicina moderna.

Theonest Ndyetabura KILIMANJARO CHRISTIAN MEDICAL CENTRE / KILIMANJARO CLINICAL RESERCH

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