AIDS/ HIV –
Current Senario
S. Jonathan Nimal
Department of Biotechnology Pondicherry University India
Objectives
• • • • Basic concepts of HIV has been dwelt. Current statistics of HIV/AIDS Current therapy available on the market Current Vaccines on trial
Purified Human Immunodeficiency Virus
Types of HIV
• HIV 1
Subtype A & D – found in sub Sahara Africa Subtype B – found in US & Canada Subtype C – found in South Africa & India Subtype E – found in south east Asia Subtype G & H - found in Russia & Central Africa Subtype I – found in Cyprus
• HIV 2
HIV Life cycle
Entry Reverse Transcription Integration Cleavage Assembly & Budding
WHO classification of clinical stages of infection
• Children – Three stages • Adults & Adolescents – Four stages
WHO Clinical stage I in Children
• Asymptomatic • Generalized lymphadenopathy
WHO Clinical stage II in Children
• Unexplained chronic diarrhoea • Severe persistent or recurrent candidiasis outside the neonatal period • Weight loss or failure to thrive • Persistent fever • Recurrent severe bacterial infection
WHO Clinical stage III in Children
• AIDS – defining opportunistic infections • Severe failure to thrive • Progressive encephalopathy • Malignancy • Recurrent septicaemia or meningitis
WHO Clinical stage I in Adults & Adolescents
• Asymptomatic • Persistent generalized lymphadenopathy • Performance scale 1: asymptomatic, normal activity
WHO Clinical stage II in Adults & Adolescents
• • • • Weight loss, <10% of the body weight Minor mucocutaneous manifestations Herpes Zoster within the last 5 years Recurrent upper respiratory tract infections • Performance scale 2: symtomatic, normal activity
WHO Clinical stage III in Adults & Adolescents
• Weight loss, >10% of the body weight • Unexplained chronic diarrhoea >1 month • Unexplained prolonged fever (interminant or constant) >1 month • Oral candidiasis (thrush) • Pulmunary tuberculosis • Severe bacterial infection • Performance scale 3: bed-ridden, >50% of the day during the last month
WHO Clinical stage IV in Adults & Adolescents
• • • • • • • • • HIV wasting syndrome Pneumocystis carinii pneumonia Toxoplasmosis of the brain Cryptosporidiosis with diarrhoea Cryptococcosis, extra pulmonary Atypical mycobacteriosis Salmonella septicaemia Progressive multifocal leukoencephalopathy Performance scale 4: bed-ridden, >50% of the day during the last month
WHO Clinical stage IV in Adults & Adolescents (Cond.)
• Cytomegalovirus disease of an organ other than liver, spleen or lymph nodes. • Hepes simplex virus infection, mucateneous >1 month, or visceral any duration • Progressive multifocal leukoencephalopathy • Any disseminated endemic mycosis (I.e. histoplasmosis, coccidiodomycosis) • Candidiasis of the oesophagus, trachea, bronchi or lungs • Lymphoma • Kaposi’s sarcoma
Global Estimates for adults and children, end 2003
• People living with HIV/AIDS – 40 million (34 – 46 million) • New HIV infections in 2003 – 5 million (4.2 – 5.8 million) • Deaths due to HIV/AIDS in 2003 – 3 million (2.5 – 3.5 million)
Estimated number of newly infected adults and children with HIV during 2003
Eastern Europe & central Asia Western Europe 180 000 – 280 000 30 000 – 40 000 East Asia & Pacific 150 000- - 270 000 North Africa & Middle East South & South East Asia 43 000 – 67 000 610 000- 1.1 million
North America 36 000 – 50 000
Caribbean
45 000 – 80 000
South America 120 000 – 180 000
Sub–Saharan Africa 3.0 – 3.4 million
Australia & New Zealand 700 – 1 000
Estimated number of adults and children with HIV/AIDS, end 2003
Western Europe 520 000 – 680 000 North Africa & Middle East 470 000 – 730 000 Eastern Europe & central Asia 1.2 – 1.8 million East Asia & Pacific 700 000 – 1.3 million
North America 790 000 – 1.2 million
Caribbean 350 000 – 590 000
South & South East Asia 4.6 – 8.2 million
Latin America 1.3 – 1.9 million
Sub – Saharan Africa 25.0 – 28.2 million
Australia & New Zealand 12 000 – 18 000
Estimated adult and child deaths due to HIV/AIDS during 2003
Eastern Europe & central Asia 23 000 – 37 000 East Asia & Pacific 32 000 – 58 000 South & South East Asia 330 000 – 590 000
North America 12 000 – 18 000
Caribbean 30 000 – 50 000 Latin America 49 000 – 70 000
Western Europe 2 600 – 3 400 North Africa & Middle East 35 000 – 50 000
Sub – Saharan Africa 2.2 – 2.4 million Australia & New Zealand < 100
Types of HIV Drugs
• • • • • Entry inhibitors Reverse Transcriptase inhibitors Integrase inhibitors (On study) Protease inhibitors Assembly & budding inhibitors (On study)
Entry inhibitors
• Fusion inhibitor • Fuzeon (enfuvirtide, or T-20)
Reverse Transcriptase Inhibitors
• Nucleoside reverse transcriptase inhibitors
(NsRTIs)
Zidovudine(ZDV, AZT) Didanosine (ddl) Stavudine (d4T) Lamivudine (3TC) Abacavir (ABC)
• Non - nucleoside reverse transcriptase inhibitors
(NsRTIs)
Nevirapine (NVP) Efavirenz (EFZ)
• Nucleotide reverse transcriptase inhibitors
(NtRTIs)
Tenofovir disoproxil fumarate
Protease Inhibitors
Saquinavir (SQV) Ritnovir (RTV) Indinavir (IDV) Nelfinavir (NFV) Lopinavir/retinavir (LPV/r)
AIDS Vaccine
• Two vaccines on trial
AIDSVAX B/B – tested in North America & Amsterdam AIDSVAX B/E – tested in Thailand
Each mixed the surface proteins (gp120) from two strains of HIV
New vaccines on human trial
• tgAAC09 – begun in Belgium • Single shot vaccine • Uses Targeted Genetics ‘ rAAV (recombinant adeno associated viral vector) Technology
New DNA vaccines on human trial
• Vaccine - ADVAX • Vaccine is tailored for C strain of HIV • Worked by The Aron Diamond AIDS ResearchCenter & International AIDS Vaccine initiative • Trail in New York & Rochester • Developed on synthetic DNA based on the genetic material available • Safe to use
sammyc2007 4/10/2008 |
31 |
0 |
0 |
educational
sammyc2007 4/17/2008 |
21 |
0 |
0 |
educational
sammyc2007 4/9/2008 |
37 |
0 |
0 |
educational
sammyc2007 4/10/2008 |
27 |
0 |
0 |
educational
sammyc2007 3/27/2008 |
77 |
2 |
0 |
educational
sammyc2007 3/27/2008 |
75 |
1 |
0 |
educational
sammyc2007 3/27/2008 |
91 |
3 |
0 |
educational
sammyc2007 4/15/2008 |
33 |
1 |
0 |
educational
sammyc2007 4/24/2008 |
29 |
0 |
0 |
educational
sammyc2007 4/25/2008 |
73 |
2 |
0 |
educational
sammyc2007 4/9/2008 |
46 |
0 |
0 |
educational
sammyc2007 3/27/2008 |
106 |
1 |
0 |
educational
sammyc2007 4/16/2008 |
20 |
0 |
0 |
educational
sammyc2007 4/16/2008 |
63 |
2 |
0 |
educational
sammyc2007 4/17/2008 |
20 |
0 |
0 |
educational
sammyc2007 6/13/2008 |
63 |
4 |
0 |
legal
sammyc2007 6/13/2008 |
52 |
0 |
0 |
legal
sammyc2007 6/13/2008 |
85 |
4 |
0 |
legal
sammyc2007 6/13/2008 |
70 |
2 |
0 |
legal
sammyc2007 6/13/2008 |
125 |
1 |
0 |
legal
sammyc2007 6/13/2008 |
96 |
0 |
0 |
legal
sammyc2007 6/13/2008 |
66 |
0 |
0 |
legal
sammyc2007 6/13/2008 |
43 |
0 |
0 |
legal
sammyc2007 6/13/2008 |
148 |
0 |
0 |
legal
sammyc2007 6/13/2008 |
54 |
0 |
0 |
legal