AIDS/ HIV – Current Senario

1. AIDS/ HIV – Current Senario S. Jonathan Nimal Department of Biotechnology Pondicherry University India

2. Objectives • Basic concepts of HIV has been dwelt. • Current statistics of HIV/AIDS • Current therapy available on the market • Current Vaccines on trial

3. Purified Human Immunodeficiency Virus

4. 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

5. HIV Life cycle Entry Reverse Transcription Integration Cleavage Assembly & Budding

6. WHO classification of clinical stages of infection • Children – Three stages • Adults & Adolescents – Four stages

7. WHO Clinical stage I in Children • Asymptomatic • Generalized lymphadenopathy

8. 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

9. WHO Clinical stage III in Children • AIDS – defining opportunistic infections • Severe failure to thrive • Progressive encephalopathy • Malignancy • Recurrent septicaemia or meningitis

10. WHO Clinical stage I in Adults & Adolescents • Asymptomatic • Persistent generalized lymphadenopathy • Performance scale 1: asymptomatic, normal activity

11. 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

12. 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

13. 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

14. 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

15. 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)

16. Estimated number of newly infected adults and children with HIV during 2003 Eastern Europe & central Asia 180 000 – 280 000 Western Europe 30 000 – 40 000 East Asia & Pacific 150 000- - 270 000 North Africa & Middle East 43 000 – 67 000 Caribbean 45 000 – 80 000 South & South East Asia 610 000- 1.1 million North America 36 000 – 50 000 Sub–Saharan Africa 3.0 – 3.4 million South America 120 000 – 180 000 Australia & New Zealand 700 – 1 000

17. Estimated number of adults and children with HIV/AIDS, end 2003 Eastern Europe & central Asia 1.2 – 1.8 million Western Europe 520 000 – 680 000 North America 790 000 – 1.2 million East Asia & Pacific 700 000 – 1.3 million North Africa & Middle East 470 000 – 730 000 South & South East Asia 4.6 – 8.2 million Caribbean 350 000 – 590 000 Sub – Saharan Africa 25.0 – 28.2 million Latin America 1.3 – 1.9 million Australia & New Zealand 12 000 – 18 000

18. Estimated adult and child deaths due to HIV/AIDS during 2003 Eastern Europe & central Asia 23 000 – 37 000 Western Europe 2 600 – 3 400 North America 12 000 – 18 000 East Asia & Pacific 32 000 – 58 000 North Africa & Middle East 35 000 – 50 000 Caribbean 30 000 – 50 000 South & South East Asia 330 000 – 590 000 Sub – Saharan Africa 2.2 – 2.4 million Latin America 49 000 – 70 000 Australia & New Zealand < 100

19. Types of HIV Drugs • Entry inhibitors • Reverse Transcriptase inhibitors • Integrase inhibitors (On study) • Protease inhibitors • Assembly & budding inhibitors (On study)

20. Entry inhibitors • Fusion inhibitor • Fuzeon (enfuvirtide, or T-20)

21. 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

22. Protease Inhibitors • Saquinavir (SQV) • Ritnovir (RTV) • Indinavir (IDV) • Nelfinavir (NFV) • Lopinavir/retinavir (LPV/r)

23. 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

24. New vaccines on human trial • tgAAC09 – begun in Belgium • Single shot vaccine • Uses Targeted Genetics ‘ rAAV (recombinant adeno associated viral vector) Technology

25. 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