Introduction to ARV therapy Principles of ARV Therapy Introduction to ARV therapy HAIVN Havard Medical School AIDS Initiative in Vietnam Basic training course for nurses - HAIVN Introduction to ARV therapy - ENG Revised 9/2012

Principles of ARV Therapy Learning objectives By the end of this session, participants should be able to: Present the goals of ARV therapy Outline ARV drugs used in Viet Nam Instruct patients on medication adherence Recognize common and/ or significant side effects of ARV drugs

Principles of ARV Therapy What are the goals of ARV therapy? Why do we use ARV drugs knowing they don’t eliminate HIV? ASK participants the questions on slide ALLOW time for them to respond USE their answers and discussions to go to next slide

Principles of ARV Therapy Goals of ARV therapy Ultimately: Improve patient’s quality of life Reduce HIV replication in patient: Reduce viral load Lessen attack of the virus on the immune system Create opportunities for the immune system to recover: Help increase the number of CD4 cells EXPLAIN that the improvement of quality of life helps them be able to carry out works involving family, hobby and friends. Improve their ability to perform daily activities to help them be active, independent social members doing paid works

Relationship between CD4 count and viral load HIV RNA (viral load) = Speed of train Slow: <5,000 Fast: 50,000+ CD4 count = Distance to crash EXPLAIN that progression of HIV is analogous to the speed of a train which is racing towards a cliff Speed of train is analogous to viral load, and distance to crash is analogous to CD4 count. The cliff represents the development of AIDS-defining conditions. If the patient is initially treated with highly active ARV therapy (HAART), viral load reduces (speed of train slows down), CD4 count increases (the distance lengthens) and the train moves backwards and far from the cliff (improve patient’s health, life ….).

Results of decrease in viral load and increase in CD4 count Principles of ARV Therapy Results of decrease in viral load and increase in CD4 count Prevent the progression from HIV to AIDS Prevent opportunistic infections Increase survival rate Decrease HIV transmission

Principles of ARV Therapy Effect of ARV HIV uses CD4 cell as a “factory” to produce HIV ARV goes into the “factory” and reduces its ability to “produce” HIV When patient takes ARV, virus production can be minimized CD4 EXPLAIN that CD4 represents the factory because: Usually HIV uses CD4 as a factory. There are machines and equipment in the factory (CD4). Virus goes into the factory, uses machines of CD4 cell and starts to replicate. Millions of new viruses are produced and get out of the factory (CD4). ARV drugs inhibit the replication of virus in CD4 cell. Consequently new virus can’t be “produced” and therefore there are fewer viruses that infect and destroy other CD4 cells.

Why do we have to combine drugs in treatment? Principles of ARV Therapy Why do we have to combine drugs in treatment? Each patient is infected with different strains of HIV Each strain of HIV is sensitive to some but not all ARV drugs To achieve the best and the longest effect, patient has to take at least 3 different ARV drugs RECALL natural progression of HIV. When entering human body there are 4 stages to form new viruses and there are many ARV drugs, each group inhibits one stage of development, and studies show can be ineffective with development of resistance if using only 1 or 2 ARV drugs. Must take at least 3 ARV drugs to inhibit effectively the development of HIV

Progression to AIDS according to ARV therapy Principles of ARV Therapy Progression to AIDS according to ARV therapy % Month Non therapy Mono therapy 15 Dual therapy Triple therapy EXPLAIN that history of treatment in USA and Europe has shown some real-life experiences. In the diagram there are 4 lines pointing out : Mono therapy is not better than non therapy and can limit future treatment options due to the development of drug-resistant HIV. Dual therapy prevents the progression in a few months, but then it continues to progress. These patients can also develop resistant strains. Triple therapy is the best, strongest and prevents the progression to AIDS in many years if patients take medications according to the regimen with absolute adherence.

ARV drugs currently available in Viet Nam Principles of ARV Therapy ARV drugs currently available in Viet Nam Nucleoside/ Nucleotide RTI AZT / Zidovudine d4T / Stavudine 3TC / Lamivudine ddI / didanosine ABC / Abacavir TDF / Tenofovir Protease inhibitors RTV / Ritonavir IDV / Indinavir LPVr / Lopinavir + ritonavir Non-nucleoside RTI NVP /Nevirapine EFV / Efavirenz EXPLAIN that all drugs listed above are ARV drugs currently used in Viet Nam. There are fewer drugs available in Viet Nam than in some other countries, but these drugs are equally effective and rather similar to drugs of the first line regimen in rich countries. Drugs are often written using 3 letter abbreviation before their full name. This is just a convenient way to write and refer to medication.

First line ARV regimens in Viet Nam Principles of ARV Therapy First line ARV regimens in Viet Nam + Lamivudine (3TC) Tenofovir (TDF) Zidovudine (AZT) Efavirenz (EFV) Nevirapine (NVP) Stavudine (D4T) is no longer recommended as a first line ARV drug Modified and Supplemented from Guidelines for Diagnosis and Treatment of HIV/AIDS,11/2011 EXPLAIN that the first line ARV regimens in Vietnam comprise of 2 NRTIs plus one NNRTI. EXPLAIN that from November 2011, the Ministry of Health no longer recommends the use of d4T. Therefore there are 3 NRTIs and 2 NNRTIs recommended as 1st line ARV drugs

Principles of ARV Therapy Side effects of ARV ASK participants to “Outline common side effects of ARV” ALLOW time for them to respond USE their answers to go to next slides

Principles of ARV Therapy Side effects of ARV (1) Side effects can happen when taking ARVs Usually in the first weeks of therapy improve over time or with symptomatic management Side effects can be mild or severe Some side effects relate to dosage and/or drug interactions EXPLAIN that patient needs to be counseled to inform doctor when side effects appear. Patient will adhere better to the treatment if they are counseled about possible side effects.

Principles of ARV Therapy Side effects of ARV (2) Common side effects: Peripheral neuropathy Diarrhea Rash Nightmare Uncommon but severe side effects : Pancreatitis Bone marrow suppression Severe rash hypersensitivity Nurse should instruct patients to recognize side effects of ARV

Some examples of side effects of ARV Principles of ARV Therapy Some examples of side effects of ARV

Allergy to Nevirapine (1) rash EXPLAIN that allergy to Nevirapine causes rash on the trunk and extremities. These photos are of 2 patients at the 05-06 center in Ho Chi Minh city.

Allergy to Nevirapine (2) Stevens-Johnson syndrome EXPLAIN that this is Stevens-Johnson syndrome – a severe allergic reaction to nevirapine. Patient has oral lesions with fever and general rash. This can progress very quickly and be fatal. Immediate discontinuation of the offending medicine is necessary.

Allergy to Nevirapine (3) Stevens-Johnson syndrome EXPLAIN that this photo is of a patient in An Giang province with Stevens-Johnson syndrome due to Nevirapine. Patient had exfoliation of skin all over the body. Patient recovered quite well when stopping ARV for 1-2 months.

Allergy due to Efavirenz Hội chứng Stevens-Johnson EXPLAIN that Efavirenz can also cause Stevens-Johnson syndrome, but more rarely than nevirapine. Both nevirapine and efavirenz belong to the same class (NNRTI). A patient who has Stevens-Johnson syndrome due to an NNRTI should never use another NNRTI.

Allergy to Cotrimoxazole (1) Allergy to cotrimoxazole may cause erythematous rash, flat or slightly elevated lesions on the trunk and extremities 20

Allergy to Cotrimoxazole (2) Rash EXPLAIN that these photos are of 2 patients who are showing their rash due to allergy to Cotrimoxazole. 21

Principles of ARV Therapy Adherence ASK participants “Meaning of Treatment Adherence” and “Content of Treatment Adherence” ALLOW time for them to respond USE their discussion to go to the next slide

Principles of ARV Therapy Adherence Adherence means taking the correct medications, in proper doses 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. EXPLAIN that patient has to take medicine for the rest of their life, and adherence is very difficult but necessary to be above 95% INSTRUCT patient to take medicine at the right time Example: take medicine 2 times a day, 12 hours apart, for instance, 8am and 8pm or 7am and 7pm… INSTRUCT patient in case they forget to take medicine at the right time: If they remember 1-2 hours after the time, take it right away and take the next dose on time. If they remember 3-4 hours after the time, take it right away and take the next dose 2 hours after the appointed time, then at the appointed time…

Non adherence to ARV therapy is common Principles of ARV Therapy Non adherence to ARV therapy is common Assessments of rates of non adherence to treatment range from 20% to 80%, with the average rate of 50%. Adherence rate in IDUs (40% - 80%) and non-IDUs (30% - 70%) are similar. ASK participants how many of them have difficulty to complete their last antibiotic regimen when they were prescribed? EMPHASIZE that non-adherence to HIV treatment is common even with patients who don’t have to face major obstacles/ difficulties in life such as working, taking care of family… Though non adherence is not only a problem for IDUs but also for the group of people belonging to lower socioeconomic status (often accompanied by addiction), IDUs usually exaggerate this problem.

Common levels of adherence Three types of patient’s adherence Adherence Treatment time (month) 100% 0% 12 24 Very good adherence Reduced adherence Non adherence Howard AIDS 2002; Ickovics Antiviral Ther 2002; Moss CID 2004 EXPLAIN that this diagram describes the adherence, and as it was stated in the previous slide and from result of the research there are 3 types of patient’s adherence The uppermost line shows very good adherence (not able to be 100% during 24 months) Middle line: reduced adherence, the diagram shows clearly changes in patient’s adherence Bottom line: represents non adherent patients who stopped taking medicines after enrolling in the study

Common reasons for non adherence to ARV Principles of ARV Therapy Common reasons for non adherence to ARV Reason % Simply forgot or were busy 66% Not at home 57% Had a change in daily routine 51% Slept through dose time 40% Sick 28% Sad, sorrowful 18% Individual problems 14% Side effects 12% EXPLAIN that there are 8 top reasons reported about non adherence in research on non IDUs. EXPLAIN that for IDUs adherence is extremely difficult because: They have a lot of disturbance in their life. They have difficulties with mental illness, sadness, homelessness, as well as the psychological impacts of illicit drug use.

Factors influencing non adherence to HIV treatment Principles of ARV Therapy Factors influencing non adherence to HIV treatment Medications interfere with daily life Drinking alcohol or using drugs Sad mood, stress Pessimistic about HIV Treatment is less effective than desired ASK participants if “there is other factor different from the list above affecting the adherence especially for IDUs” ALLOW time for them to respond USE their answers and discussions to explain more about affecting factors EXPLAIN that difficulty with adherence is a common problem, but it is more difficult to IDUs, therefore there need to be a lot of ways to support IDUs to maintain treatment adherence.

Goals of adherence to ARV drugs Principles of ARV Therapy Goals of adherence to ARV drugs Maximizes inhibition of viral load Reduces drug resistance Increases time of exposure to effective medication Above all, helps: Delay progression to AIDS Prolong survival Improve quality of life Goals or benefits???

Components of adherence Principles of ARV Therapy Components of adherence Take medicine on time Maintain regular check up Maintain “healthy lifestyle with HIV” Eat healthy food Exercise regularly Do not smoke tobacco or drink alcohol EXPLAIN that we need to pay attention to components of adherence to support patient appropriately in different communities.

Nurse should pay attention to Principles of ARV Therapy Nurse should pay attention to

Learn about the patient (1) Principles of ARV Therapy Learn about the patient (1) Find out attitudes, knowledge and beliefs of the patient by asking questions : About medication generally: For example: Did you take medication before? Tell me about that. About HIV/AIDS: For example: Can HIV be cured? GIVE a few questions to help participants learn more about the attitudes, knowledge and beliefs of the patient: Have you ever had to take medicine? Why did you have to take medicine? Tell us the name of drug if you remember? Did you have prescription or not? Did you follow the prescription or just take medicine a few days ...? Why did you not follow the prescription? You knew that you were HIV infected and wanted to have medications? You know that HIV can be cured? Why do you need to have ARV therapy?

Learn about the patient(2) Principles of ARV Therapy Learn about the patient(2) About ARV drugs: Do you know someone who is on ARV therapy? How is his/ her health after taking ARVs? What would happen if you take ARV drugs? Patient’s desires: benefit and cost of treatment changes in appearance (or not) side effects EXPLAIN that medical staff who works with patients in preparation for ARV therapy needs to understand their patients to support them the best possible

Learn about the life circumstances of the patient (1) Principles of ARV Therapy Learn about the life circumstances of the patient (1) Has patient ha disclosed his / her HIV status to anyone? Who is the main support person for the patient? Does s/he know that the patient has HIV? What does s/he know about ARV drugs? EXPLAIN that healthcare workers need to understand the patients’ life circumstances to find the most appropriate and effective way to support them

Learn about the life circumstances of the patient (2) Principles of ARV Therapy Learn about the life circumstances of the patient (2) Life circumstance Have a house? Is anyone in the family aware of the patient's diagnosis? Are there any children at home? Daily living work? child care? EXPLAIN that healthcare workers need to understand the patients’ life circumstances to workers need to understand the patients’ life circumstances to For example: Can the patient stay with family or friends or does s/he wander from house to house? Does the patient have a job with steady income?

The role of nurses in ARV therapy groups (1) Principles of ARV Therapy The role of nurses in ARV therapy groups (1) Instruct patients on ARV therapy purposes Understand how ARV impacts patients’ lives Collaborate with physicians and pharmacists in ARV therapy group to give patients the best care EXPLAIN that nurses working in ARV therapy group should have: knowledge about HIV, AIDS counseling skills, instruct and support patients ability to coordinate with colleagues to achieve the best results in patient care

The role of nurses in ARV therapy groups (2) Principles of ARV Therapy The role of nurses in ARV therapy groups (2) Ensure that patients: understand how to take medicine before leaving the clinic have plans to remember to take medicine Instruct patients on: possible side effects what to do if side effects occur Give patients and their families a message of: HOPE EXPLAIN that nurses working in ARV therapy groups need to support patients to achieve all the objectives on the slide.

Principles of ARV Therapy Key points The goal of ARV treatment is to reduce viral load and increase CD4 count and ultimately to increase quality of life A 3-drug combination is most effective The role of nurses is to help patients adhere to treatment to obtain the best results from ARVs

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