1. April 15 Understanding HIV Treatment and adherence. The African Eye Trust HIV Treatment Information Event By Badru Male&Elijah Amooti

2. April 15 Understanding HIV Treatment and adherence. Background  HIV discovered within Gay communities in San Francisco, USA in 1982 as HTLV1.  1984 rediscovered in heterosexuals in Central Africa  In France, a scientist discovered that HIV causes AIDS.  1988 – Use of septrin to cure PCP and HIV encephalopathy/Toxoplasmosis  AZT Monotherapy

3. April 15 Understanding HIV Treatment and adherence. The UK HIV deaths Trend  2006 - 5,505 new diagnoses of HIV ( about 50% acquired in Africa )  84,730 Cumulative since 1982 ( 33% do not know they are HIV positive)  40% People of African ethnicity (about 24,000)

4. April 15 Understanding HIV Treatment and adherence. The UK HIV deaths Trend  1995-1800 deaths  2000-500 deaths  2006-419 deaths (down by 15%)  22,745 Cumulative deaths

5. April 15 Understanding HIV Treatment and adherence. HIV and AIDS diagnoses and deaths in HIV infected individuals, UK reports to end December 2006 Numbers, particularly for recent years, will rise as further reports are received.

6. April 15 Understanding HIV Treatment and adherence. History of HIV Anti-Retroviral Therapy (ART)  Nucleoside analogues –1988, A drug called Zidovudine (AZT) used to treat HIV infection. –1989, Videx (DdI) –1990, Hivid (DdI)  Non-nucleoside analogues (1989) (Nevirapine/ viramune)

7. April 15 Understanding HIV Treatment and adherence. History of HIV Anti-Retroviral Therapy (ART)  1995 Protease inhibitors (PI)  Combination Therapy – Vancouver (1998)  1999 – Tenofovir (Nucleotide analogue)  2001- Entry inhibitor – T/20 (Fuzeon)  2005 - Entry CCR5 receptors

8. April 15 Understanding HIV Treatment and adherence. Anti-Retro-Viral classes of drugs  Nucleoside analogues (NUKES)  Non-Nucleoside analogues (NON-NUKES)  Protease Inhibitors (PIs)  Entry/Fusion Inhibitors (FIs) –CCR5 blockers  Nucleotide analogues (Nukets)  Intergrase inhibitors

9. April 15 Understanding HIV Treatment and adherence. Nukes NukesNon-nukesProteaseInhibitorsFusion/entryInhibitors Integrase Inhibitors AZTddIddCFTC3TCd4TAbacavir Tenofovir (nt) Combivir© Kivexa © Trizivir © Truvada © SustivaNevirapineDelavirdine TMC 125 IndinavirSaquinavirLopinavir Fosampren avir RitonavirAmprenavir Kaletra © NelfinavirAtazanavirTipranavirDuranavir(TMC114)T-20 CCR5 inhibitors GS-9137MK-0518

10. April 15 Understanding HIV Treatment and adherence. Viral Enzymes  Reverse Transcriptase  Intergrase  Protease

11. April 15 Understanding HIV Treatment and adherence. HIV Manifestation

12. April 15 Understanding HIV Treatment and adherence. Reverse transcriptase

13. April 15 Understanding HIV Treatment and adherence. Gene for envelope changes Body makes antibodies Antibodies cannot recognise virus Genetic variability/mutation Body makes new antibodies New antibodies cannot recognise virus

14. April 1514 How HIV infects T4 cells VIRUS New viruses bud out of T4 cell T4 CELL CYTOPLASM CD4 receptor molecule Enters host cell, loses envelope RT enzyme Viral RNA RNA DNA Viral DNA viral genome integrates with T4 cell genome copies of viral RNA (messenger RNA) NUCLEUS T4 cell genome

15. April 15 Understanding HIV Treatment and adherence. GROUP EXERCISE  Assume that you are one of the viral enzymes  Pick a card of a drug that you consider your enemy  Place it in the right place  Pick a friend from the other groups who will help you fight the virus and explain

16. April 15 Understanding HIV Treatment and adherence. HIV Treatment issues  Starting treatment  Adherence  Side effects/Toxicity  Drug Concentration (IQ)  Drug Resistance  Changing treatment  Drug interactions

17. April 15 Understanding HIV Treatment and adherence. STARTING HIV TREATMENT  Why start HIV treatment  When to start HIV treatment  What to start with

18. April 15 Understanding HIV Treatment and adherence. 4-8 wks Up to 12 years 2-3 years Infection Seroconversion AsymptomaticSymptomatic AIDS Death 1000 50 0 0 CD4+ Cells/mm3 viral load 200 2-12 mo 2 million 0 copies/mL Viral load & CD4 after HIV-1 Infection [without treatment ] Time

19. April 15 Understanding HIV Treatment and adherence. ADHERENCE to ARVs  The meaning – (KMS=A)  What is non-adherence  Factors affecting adherence  Support needed for adherence  Outcomes of adherence

20. April 15 Understanding HIV Treatment and adherence. What is adherence?  Knowledge –How drugs work –Why they work –Why they may not work and consequences  Memory –Biopsychosocial issues  Satisfaction –Benefits, lifestyle, Side/effects/QOL

21. April 15 Understanding HIV Treatment and adherence. After HIV treatment (ARVs): effect on CD4 and viral load 1-12 yrs+1-6 mo Chronic Infection Start treatment 1000 50 0 0 CD4+ cells/mm3 viral load (RNA) copies/mL 200 2 million 0 + 1-40+ years !! < 50 copies/mL Viral load <50 copies/mL Time

22. April 15 Understanding HIV Treatment and adherence. dose Increased risk of side effects 0 Increased risk of resistance dose Taking drugs at the exact time makes sure that you keep above a minimum level Drug levels and resistance.1 MEC (Minimum Effective Concentration) Drug concentration

23. April 15 Understanding HIV Treatment and adherence. Side Effects/Toxicity  Why it is better to know before starting.  What are “side effects” –Short term –Long Term  How to manage side effects  The balance of benefits

24. April 15 Understanding HIV Treatment and adherence. Managing side effects  Complimentary therapies –Taichi –Acupuncture –Reflexology –Shiatsu –Yoga  New fill for lipodystrophy  Exercising for high LDL

25. April 15 Understanding HIV Treatment and adherence. Changing treatment combination  Why should some one change treatment  What should someone change to  When should someone change treatment  Why are consultants usually against change

26. April 15 Understanding HIV Treatment and adherence. Drug interactions  ARVs / ARVs  ARVs / Anelgesics  ARVs /Antibacterials  ARVs / Anticonvulsants  ARVs Antivirals  ARVs / Neoplastics  ARVs / Antiprotozoals

27. April 15 Understanding HIV Treatment and adherence. Drug interactions  ARvs / Sedatives  ARVs / Gastrointestinal agents  ARVs / Illicit recreational  ARVs / Immunosuppressants  ARVs / Steroids  ARVs / Herbals  ARvs / Beta blockers  ARVs / Antipsychotics

28. April 15 Understanding HIV Treatment and adherence. New Drugs  PI – TMC114 (Darunavir, PREZISTA)  600mg/boosted with 100mg Rit. BD  NNRTI – TMC125  CCR5 Inhibitors (in pipeline) –Aplaviroc –Vincriviroc –Maraviroc  CXCR4 Inhibitors (in pipeline)  Integrase Inhibitors