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Adherence to ARV Therapy and Resistance HAIVN Havard Medical School AIDS Initiative in Vietnam 1 Learning Objectives By the end of this session, participants will be able to: Present the importance of good adherence to ARV therapy List the 5 main reasons leading to non adherence Describe 3 types of adherence Explain the relationship between adherence and drug resistance 2 Adherence 3 Definition Adherence means taking right drugs, in proper dose and on time To achieve the best effect with ARV therapy, adherence rate is required to be above 95% • Example: If medications are prescribed 2 times a day, don’t forget more than 2 doses a month. 4 Common types of adherence Three types of patient’s adherence Very good adherence Adherence 100% 0% Reduced adherence Non adherence 0 12 24 Treatment time (month) Howard AIDS 2002; Ickovics Antiviral Ther 2002; Moss CID 2004 Extended definition of adherence Any activity: support, or help to improve the health of people with HIV / AIDS pay attention to the care and treatment of people with HIV, including: • Physical health status • Mental, psychosocial well-being 6 Goals of adherence to ARV drugs Maximal inhibition of viral load Reduce drug resistance Ensure effect time of drug All above helps: • Slow progression of HIV • Prolong survival 7 Drug resistance 8 Adherence: Definition Clinical status • Improve physical health • No more opportunistic infections • CD4 count increases: Immunology* Virology • At least from 50-150 cells in the first year • Increase 50-100 cells in the second year • Viral load is undetectable after 12 months Adherence : according to Kaufman and Le Moing, WHO Non adherence: Definition Patients who do not improve on • clinical • immunologic and • viral outcome after starting ART therapy are considered not to respond to treatment 10 Non adherence: Causes Resistance leads to the failure of ARV therapy Intolerance with ARV drugs aggravates the disease Drug interactions causes ARV levels below the threshold of viral suppression 11 Drug resistance Drug level below the threshold of viral suppression Viral replication continues with the presence of drugs DRUG RESISTANCE Drug resistance is often, but not always due to non adherence How does HIV drug resistance occur? Social/ personal issues Poor quality drugs Wrong dose Host genetics Regimen issue Toxicity Poor adherence Poor absorption Insufficient drug level Rapid clearance Poor activation Viral replication in the presence of drug Drug interaction Resistant virus Transmission How does HIV develop resistance? HIV has an extremely high rate of replication The new generation of virus is little different from the previous generation Some structural changes can improve the ability of viral replication • When virus can multiply in the presence of ARV drugs, it can be said that virus is resistant to drugs 14 Effect of non adherence to the development of viral mutations Level of drugs below the threshold of treatment Wild-type virus 15 Risk of drug resistance The relationship between the level of adherence and the risk of drug resistance 0 100 % Adherence Williams & Fiedland, 1997 Resistant HIV Some comments: 50% of people living with HIV (not taking into account the current status of treatment) there is evidence for at least one drug resistance 78% of people who have HIV treatment are resistant to at least one antiviral drug CROSS-RESISTANCE: Resistance to a drug in a group often leads to resistance to another drug in that group! 17 Risk of transmission Drug resistant HIV can transmit: to new HIV infections as well as to co-infections 18 ARV therapy failure ARV therapy failure is often, but not always, due to drug resistance Failure of ARV therapy is expressed by: • Increased viral load • Reduced CD4 count + T cells • Progression to AIDS 19 Why is adherence mentioned? Good adherence will reduce the risk of the development of ARV resistance Drug resistance is a major problem • For individuals • For society 20 Key points Good adherence to ARV therapy is necessary but very difficult Non adherence results in low drug concentration in the blood and allows the development of drug resistant HIV ARV resistance leads to treatment failure Transmission of drug-resistant virus from one person to another occurs and is a public health problem 21 Thank you Question? 22