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The African Eye Trust HIV Treatment Information Event By Badru Male&Elijah Amooti May 17 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 May 17 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) May 17 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 May 17 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. May 17 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) May 17 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 May 17 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 May 17 Understanding HIV Treatment and adherence. Nukes Non-nukes Protease Inhibitors AZT ddI ddC FTC 3TC d4T Abacavir Tenofovir (nt) Combivir© Kivexa © Trizivir © Truvada © Sustiva Nevirapine Delavirdine TMC 125 Indinavir T-20 Saquinavir CCR5 inhibitors Lopinavir Fosampren avir Ritonavir Amprenavir Kaletra © Nelfinavir Atazanavir Tipranavir Duranavir (TMC114) May 17 Fusion/entry Integrase Inhibitors Inhibitors Understanding HIV Treatment and adherence. GS-9137 MK-0518 Viral Enzymes Reverse Transcriptase Intergrase Protease May 17 Understanding HIV Treatment and adherence. HIV Manifestation H IV virus entry inhi bitors C D4 cell protease i nhibi tor s nukes & non-nukes (N NRTIs) May 17 Understanding HIV Treatment and adherence. Reverse transcriptase May 17 Understanding HIV Treatment and adherence. Genetic variability/mutation Gene for envelope changes Gene for envelope changes Body makes antibodies Body makes new antibodies Antibodies cannot recognise virus May 17 Understanding HIV Treatment and adherence. New antibodies cannot recognise virus How HIV infects T4 cells VIRUS T4 CELL CYTOPLASM Enters host cell, loses envelope RT enzyme Viral RNA T4 cell genome RNA DNA copies of viral RNA (messenger RNA) Viral DNA May 17 viral genome integrates with T4 cell genome New viruses bud out of T4 cell 14 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 May 17 Understanding HIV Treatment and adherence. HIV Treatment issues Starting treatment Adherence Side effects/Toxicity Drug Concentration (IQ) Drug Resistance Changing treatment Drug interactions May 17 Understanding HIV Treatment and adherence. STARTING HIV TREATMENT Why start HIV treatment When to start HIV treatment What to start with May 17 Understanding HIV Treatment and adherence. Viral load & CD4 after HIV-1 Infection [without treatment] Death Seroconversion Infection Asymptomatic Symptomatic AIDS 2 million 1000 CD4+ Cells/mm3 viral load copies/mL 50 0 200 0 0 4-8 wks 2-12 mo Up to 12 years Time May 17 Understanding HIV Treatment and adherence. 2-3 years ADHERENCE to ARVs The meaning – (KMS=A) What is non-adherence Factors affecting adherence Support needed for adherence Outcomes of adherence May 17 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 May 17 Understanding HIV Treatment and adherence. After HIV treatment (ARVs): effect on CD4 and viral load Start treatment Viral load <50 copies/mL 2 million 1000 CD4+ cells/mm3 viral load (RNA) copies/mL 50 0 200 < 50 copies/mL 0 0 + 1-40+ years !! 1-12 yrs +1-6 mo Chronic Infection May 17 Time Understanding HIV Treatment and adherence. Drug levels and resistance.1 Taking drugs at the exact time makes sure that you keep above a minimum level Increased risk of side effects Drug concentration MEC (Minimum Effective Concentration) Increased risk of resistance 0 dose May 17 dose dose Understanding HIV Treatment and adherence. dose 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 May 17 Understanding HIV Treatment and adherence. Managing side effects Complimentary therapies – Taichi – Acupuncture – Reflexology – Shiatsu – Yoga New fill for lipodystrophy Exercising for high LDL May 17 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 May 17 Understanding HIV Treatment and adherence. Drug interactions ARVs / ARVs ARVs / Anelgesics ARVs /Antibacterials ARVs / Anticonvulsants ARVs Antivirals ARVs / Neoplastics ARVs / Antiprotozoals May 17 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 May 17 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 May 17 Understanding HIV Treatment and adherence.