FARMACI, INNOVAZIONE e INFEZIONE DA HIV / AIDS

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

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

Concorde Trial

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

Deaths per 100,000 Population Trends in Annual Rates of Death from Leading Causes of Death Among Persons 25-44 Years Old, USA, 1982-1998 40 Unintentional injury Cancer 35 30 Heart disease 25 20 Suicide 15 HIV infection 10 Homicide 5 0 82 84 86 88 National Center for Health Statistics National Vital Statistics System 90 Year 92 94 96 98* *Preliminary 1998 data Chronic liver disease Stroke Diabetes

Mortality vs. HAART Utilization 40 100 Deaths per 100 Person-Years USE OF HAART 30 75 -dpercentage ays on HA RT 25 of Patient DEATHS 20 50 15 10 25 -YDeaths ears per 100 Person 5 0 1995 Palella F et al, HOPS Study 1996 1997 1998 1999 2000 0 2001 Percentage of Patient Days on HAART 35

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I nuovi farmaci

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;100:10598-10602.

From MR Furtado et al., N Engl J Med 340:1614-1622, 1999.

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

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)

Trends in Maternal Antiretroviral Therapy and Perinatal HIV Transmission, Women and Infants Transmission Study: 1990-2004 60 100 90 50 No ART 70 40 HAART 60 Monotherapy 30 17.7% 40 22.3% 19.4% 20 30 17.5% MultiART 9.0% 10 6.6% 0 1990 50 1991 1992 1993 1994 3.6% 1995 10 3.2% 3.0% 2.1% 1996 1997 1998 Year of Enrollment 20 0.9% 1.4% 1.6% 1999 2000 2001 1.2% 2002 0 2003+ % Receiving Therapy Transmission Rate per 100 80

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

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

Leading causes of death in Africa 25.0 22.6 20.0 % of Total 15.0 10.1 10.0 9.1 6.7 5.5 5.0 4.3 3.6 3.1 2.9 2.3 0.0 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

Life Expectancy in Different African Countries Life expectancy at birth, in years 65 60 Botswana Uganda South-Africa 55 Zambia 50 Zimbabwe 45 40 35 1950-55 1955-60 1960-65 1965-70 1970-75 1975-80 1980-85 1985-90 1990-95 1995-00 Source: United Nations Population Division, 1998

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.

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

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

People on ARV therapy in developing countries 2002 2005 Thousands 1 500 North Africa and the Middle East Europe and Central Asia East, South and South - East Asia Latin America and the Caribbean 1 000 Sub - Saharan Africa 500 0 end mid- end mid- end mid- end 2002 2003 2003 2004 2004 2005 2005

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.