Brazil Conference Wednesday 4/17/13. Workshop for HIV Clinical Staff: Adherence, Clinical, and Research Issues

Transcription

1 Brazil Conference Wednesday 4/17/13 Workshop for HIV Clinical Staff: Adherence, Clinical, and Research Issues

2 Introductions Shivaun A. Celano, BS, Pharm D, MBA, AAHIVP - Research Associate in the Division of Infectious Disease at The Johns Hopkins University School of Medicine - Program Coordinator of HIV Adherence and Patient Education Services - Coordinator for Project LINK, a multidisciplinary Adherence program - Provider for adherence support as clinical pharmacist - Has worked in HIV/AIDS research/care since Disclosures or conflicts: None

3 Introductions Edward Fuchs, PA-C, MBA - Associate Director of the Drug Development Unit at Johns Hopkins - Research Associate Division of Clinical Pharmacology, Johns Hopkins School of Medicine Department of Epidemiology, Johns Hopkins School of Public Health - Involved in HIV research since Principal Investigator of pilot studies HIV Microbicide Development - Disclosures or conflicts: None

4 Introductions Jeanne Keruly, MS, CRNP - Working in HIV since Observational post -marketing study of Zidovudine - ARV Clinical trials coordinator for prison inmates - Managed the HIV Clinic - Current Director of Ryan White HIV clinical program - Medical provider in the HIV clinic - Disclosures/Conflicts: None

5 We want to know something about YOU!

6 What type of work to you do in HIV Care? A- Physician B- Pharmacist C- Nurse D- Case manager/social worker E- Outreach F- Patient advocate G- Other

7 Does part of your responsibilities in HIV care involve any type of research? A-Yes B-No

8 What about you? Have you ever participated in a clinical trial A-Yes B-No

9 Objectives Case-based interactive session By the end of the session participants can: Describe the importance of engagement in HIV care List common reasons for barriers to adherence Identify strategies to improve adherence Discuss ways in which multidisciplinary practice can promote adherence Describe some of the challenges of integrating research into HIV clinical care

10 Case #1 GG is a 35 year old female and is scheduled for a new patient appointment in the clinic on Monday She misses her appointment. When you go back to review the appointment registry, you see that this is the second time in a six month period that this woman was scheduled for a new patient appointment and didn t show!

11 Audience: What Should the Clinic Do? A -Nothing, she knows how to schedule an appointment, wait for her to make a third appointment B -Send a letter informing her that she cannot be seen in the clinic as she has missed two consecutive appointments C-Send a letter informing her that she can make another appointment, but if she misses the next appointment, will be charged a fee when and if she comes in for the appointment D-Attempt to contact her to determine interest and/or problems with coming in for the visit

12 Stages of Engagement in Care Garner, et al HIV/AIDS d CID 2011:52 (15 March

13 HIV Systems Navigation Bradford et al. AIDS Patient Care and STDs Vol 21, Supp 1, 2007,s-49-s-58.

14 The Therapeutic Implications of Timely Linkage and Early Retention in HIV Care

15 Keeping a Medical Appointment Matters Regular Attendance is Associated with Improved Survival GiodarnoP et al. Clin Infect Dis 2007; 44(11):

16 Limited Clinic Intervention and Improvement is Show Rate 1. 6 Large HIV Clinics with high noshow rates 2. Posters on the wall and patient materials; how to stay connected to the clinic and the provider 3. brief messages from all staff (professional + clerical) 4. N= 9,000 to 10,000 patients receive this over 12 months Approximately 7% Improvement in kept appointments for the clinic

17 Year to Year Improvement: Mean Percentage Appointments Kept N-INT N-PRE Overall 10,371 9,460 New Pts 1,074 1,052 Re-engager Pts Active Pts 8,997 8,110 Courtesy of Gardner, Lytt, 2012 INT % PRE % Year to Year Improvement GEEbased p-value 1.9 % < % < % < % <0.0001

18 Case # 2 JY is a 45 year old male, referred to you because he will be starting ARVs. He has been off ARV for the past 10 years due to active heroin abuse. He is now abstinent from heroin and on Methadone 130mg daily. His provider would like you to offer general HIV education as well as to prepare him for taking a new regimen. Labs: HIV viral load: 13,299 copies/ml; CD4 446 cells/mm 3 Prescribed regimen: Darunavir/Ritonavir/Emtricitabine/Tenofovir

19 Case # 2 JY reveals to you that he had lead poisoning as a child. He also admits that he is not very good at reading or writing. He lives with his elderly mother who knows his diagnosis but is unable to help with his medications. What are some of the concerns in starting treatment in this man?

20 Challenges to Successful HIV Therapy and Considerations When Initiating Therapy Replication rate - Viral load Mutation rate resistance Latent reservoirs of HIV Clinician experience Communication skills Virus Adherence Access to medication Life situation Disease stage Clinician Patient Drug Potency Pharmacokinetics (dosage schedule) Tolerability Toxicity Convenience Resistance

21 Factors Associated With Poor Adherence (1) Low levels of health literacy or numeracy (ability to understand numerical-related health information) Certain age-related challenges (e.g., polypharmacy, vision loss, cognitive impairment) Younger age Psychosocial issues (e.g., depression, homelessness, low social support, stressful life events, or psychosis) Nondisclosure of HIV serostatus Neurocognitive issues (e.g., cognitive impairment, dementia)

22 Factors Associated With Poor Adherence (2) Active (but not history of) substance abuse, particularly for patients who have experienced recent relapse Stigma Difficulty with taking medication (e.g., trouble swallowing pills, daily schedule issues) Complex regimens (e.g., high pill burden, highfrequency dosing, food requirements) Adverse drug effects Nonadherence to clinic appointments Cost and insurance coverage issues Treatment fatigue

23 Factors Associated with Good Adherence Emotional and practical supports Convenience and simplicity of regimen Understanding of the importance of adherence Belief in efficacy of medications Feeling comfortable taking medications in front of others Keeping clinic appointments Severity of symptoms or illness March

24 Provider Factors Associated with Adherence Patient s ability to trust and have confidence in provider Qualitativeanalysis 1 Good quality patient-provider relationships tended to promote adherence, lesser quality relationships impeded it 1 Roberts. AIDS Patient Care and STDs, 2002; 16:43-50

25 Patient Factors Associated with Adherence Factor Adjusted Odds Ratio 95% CI Reference Perceived self efficacy Multiple children Illicit Drug Use , Depression Gifford et al. J Acquir Immune Defic Syndr 2000; Turner et al. Med Care 2000; 38: Gordillo et al. AIDS 1999; 13: Montessori et al. 7 th CROI, San Francisco 2000

26 Case # 2 (continued) JY begins his new ARV regimen with help from you which consists of education and pillbox fill and returns in 1 week for adherence and side effect assessment. Questions: What education should be provided to this patient? How much adherence is enough? How do you measure adherence?

27 Improving Adherence: Medication Education Planned, simple, modified based on literacy level, repetitive Written and verbal instructions on: CD4/VL/where drugs work/resistance/patient medication schedule/medication information sheets HAART/prophylaxis & all medications goals of therapy -what and when to expect how to take potential side effects side effect management what to do for missed doses drug interactions, etc

28 How Much Adherence is Enough in HIV? Adherence to HAART VL <500 >95% adherence 81% 90-95% adherence 64% 80-90% adherence 50% 70-80% adherence 24% <70% adherence 6% Adherence to HAART VL<500 95% -100% 84% 90% -<95% 64% 80% -<90% 47% 70% -<80% 24% < 70% 12% ICAAC, 1998 Abstract I-172 (99 VA pts -MEMS report) Low-Beer et al 2000 monthly Rx refill data (886 ART naïve) In most diseases, a successful adherence rate is defined as > 80% of doses are taken, or > 80% of prescriptions are filled on time

29 How Many Doses = 95% Adherence? QD Regimen miss 0 doses in 1 week (0 out of 7) miss 0 doses in 2 weeks (0 out of 14) miss 1 dose in 1 month (1 out of 30) BID Regimen miss 0 doses in 1 week (0 out of 14) miss 1 dose in 2 weeks (2 out of 28) miss 3 doses in 1 month (3 out of 60)

30 How do we Measure Adherence? No Gold Standard Provider Estimates Patient self-report Diaries Pill Count Laboratory Markers Electronic Devices Pharmacy Records

31 MEMS versus Self Report Self report overestimates level of adherence % patients with VL<400 (method of report) Adherence MEMS Self-report >95% 80% 63% 70-95% 60% 33% 50-70% 33% 13% <50% 10% 0% 67pts with IVDU hx, 1day & 1 week prior to clinic visit Arnsten, et al, 7th Retrovirus (2000) Abstract 69

32 Measuring Adherence: Pill Counts Advantages: more objective than patient report correlates better with electronic bottle caps than does self-reported adherence 1 Drawbacks: many patients forget to bring their bottles patients can still exaggerate adherence time consuming patients may find it too paternalistic does not reveal patterns of missed doses 1. Golin C, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago. Abstract 95

33 Measuring Adherence: Diaries In theory, better than relying on memory in practice, not very useful many patients do not fill them in 1 those that do may do so immediately before office visit 1. Golin C, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago. Abstract 95.

34 Provider versus MEMS Clinicians overestimate level of adherence 25% of patients who took 80% or less of their protease inhibitor therapy had been estimated to be more than 90% adherent by their medical provider Miller, et al, 6th Retrovirus (1999) Abstract 97

35 Case #2 (continued) A researcher is interested in recruiting JY for a drug interaction study involving his current treatment regimen and a new formulation of methadone. The clinic provider does not want JY to enroll in the study. What can the researcher do to encourage JY s enrollment? What are the some of the other issues that are important to consider for JY?

36 The Top Five Reasons Doctors Don't Refer Patients Into Clinical Trials 31% Lack of information on treatments and new investigational drugs 15% Trials are not appropriate for my particular practice 13% Not enough time to learn about a particular trial 10% Lack of access to information 7% Fear of losing a patient Source: MacDonald; CenterWatch 2006

37 The Belmont Report Beneficence Maximize benefits/minimize harms Justice Treat people fairly and design research so that burdens and benefits are shared equally Respect for Persons Subjects enter into the research voluntarily and with adequate information.

38 Potential Advocacy Conflicts for Study Coordinators Primary commitment Patient Advocate Subject Advocate Study Advocate Assure patient welfare Assure welfare of individual as a research subject Advance research goals by gathering valid, clean data, including attention to subject recruitment and retention Davis AM, et al J Law, Med &Ethics, 2002

39 Case #3 MM 26 year old black male with newly diagnosed HIV infection Presented in ER with swollen glands and given HIV test Last negative HIV test was in 2008 HIV risk behavior: MSM CD4 cell count: 347 cells/mm 3 HIV-1 viral load: 18,500 copies/ml HIV Genotype: No resistance detected

40 Case #3 (continued) Hepatitis B and C negative Social History: Non smoker Unemployed Living with sister and her husband Parents died of complications of drug use At presentation for the appointment Tearful throughout the interview and exam Reports not being able to sleep since learning about his diagnosis

41 Questions-Case # 3 Should this man be treated? What would be the concerns about starting treatment? What would need to be addressed before treatment is initiated?

42 Improving Adherence: before Initiation of Therapy Assess patient's understanding and acceptance of his HIV diagnosis Identify potential barriers before starting Manage or refer for treatment of adherencelimiting co-morbid conditions Depression Engage family or friends when possible Ask the patient- Do you feel that you can take HIV medications 1-2 times a day every day?

43 Involve the Patient in ARV Regimen Selection For each option: review regimen potency potential side effects dosing frequency pill burden storage requirements food requirements consequences of nonadherence (Shivaun planning her next visit with the patient)

44 Key Points Patients should understand that their first regimen usually offers the best chance for a simple regimen that affords long-term treatment success and prevention of drug resistance. Effective response to ART is dependent on good adherence. Clinicians should identify barriers to adherence such as-a patient s schedule, competing psychosocial needs, learning needs, and literacy level beforetreatment is initiated. As appropriate, resources and strategies that will help the patient to achieve and maintain good adherence should be employed. Individualizing treatment with involvement of the patient in decision making is the cornerstone of any treatment plan.

45 Questions-Case # 3 (Continued) MM has a steady partner and by report, he does not have HIV infection What are the concerns for the partner? Is there anything that we can offer to support the partner remaining healthy? Would an HIV prevention study be appropriate for MM s partner?

46 Pre-Exposure Prophylaxis (PrEP) iprex Trial Once daily Emtricitabine/Viread for HIV prevention in Gay and Bisexual men Consistent use of PrEp was needed Data was obtained through self report, bottles dispensed and pill counts >90% adherence = risk decrease 73% <90% adherence = risk decrease 21%

47 What do you think would motivate MM s partner to join the Study? A- Help scientists find a prevention for HIV B-Reduce his own risk for getting HIV C-The chance to get the best prevention scientists have to offer D-No cost for the medication E- Close monitoring by doctors F- Other

48 Every hour 300 new HIV infections 5 Minutes 25 n Population Equivalence Johns Hopkins Presenters 2.8 hours 1,000 Brazil Hopkins conference 16.4hours (0.7d) 4,931 Daily number of tourists to Corcovado 2,063 hours (86d) 160,000 Number of Copacabana residents

49 Benefits and Burdens Research Participation Ulrich CM, et al AJOB Primary Research, 2012

50 I feel as though I am working with them and not for them. We have the same common goal in mind, the hope that someday HIV will just be a memory.

51 Comparing Self-report versus drug concentration What the research volunteers said they did Hosek SG, et al J Acq Immune Defic Syndr, 2013

52 Case # 4 ARis a 30 year old female referred to you because her VL has increased and her CD4 has dropped while on ARV. Current Labs: HIV viral load 52,000 copies; CD4 cells 89/mm 3 HIV genotype: no resistance detected Current regimen: Atazanavir/Ritonavir/Emtricitabine/Tenofovir

53 How would approach the question of missing doses of ARVs? A. You didn t stop taking your medications, did you? B. Do you take all your medications? C. How good of a job did you do with taking your medications in the last 30 days? D. Are you having any problems with taking your medications?

54 Patient-Reported Reasons for Non-Adherence % of Patients Reporting Busy/Forgot 52% Away from home 46% Change in routine 45% Depressed/overwhelmed 27% Drug holiday/break from meds 20% Ran out 20% Too many medicines 19% Worried about becoming immune to meds 19% Drug too toxic 18% Avoid side effects 17% Don't want others to notice 17% Taking HIV drugs is reminder of HIV 16% Gifford et al. J Acquir Immune Defic Syndr 2000;

55 Treatment is lifelong Challenges Many patients will initiate therapy when they are generally in good health, feel well, and demonstrate no obvious signs or symptoms of HIV disease Adherence is affected by many factors: characteristics of: the patient, the regimen, the clinical setting, the provider/patient relationship.

56 Challenges: Decline of Adherence Drug Adherence Declines Over Time -Patterns by Drug Class Over 1 Year Period % Reporting 100% Adherence PI NNRTI NRTI 1 Month 4 Months 8 Months 12 Months [Mannheimer et al. CID 2002;34: ]

57 What do you do with AR? Try to determine why the patient is nonadherent. You determine that the patient has MAJOR issues with disclosure what now? The patient also reveals that she is having difficulty with accepting her diagnosis and feels that she has no one to talk to about this what now?

58 Case #4: AR Responses I take all of my medications as prescribed! I live in my home with my 4 children and I am unemployed. Further questioning reveals that AR s children do not know her diagnosis and that AR has not been taking her meds as prescribed because she is afraid that her children will find out about her HIV diagnosis if they see her medications. She also reveals that she is afraid that she will die from AIDS and has no one to talk to about this.

59 To Improve Adherence, Categorize Non-adherence Psychosocial barriers? Address attitudinal or cultural beliefs Address language barriers (e.g., for non-english-speaking patients) Establish or improve doctor-patient relationship Systemic barriers? Address healthcare-system impediments Establish or improve healthcare-team relationship Educational barriers? Identify knowledge gaps Anticipate patient misunderstanding of instructions and ask patients to repeat instructions back in their own words

60 Improving Adherence: Support Interventions Peer-based Medication Delivery (DOT) Readiness Adherence integrated into HIV primary care vs dedicated adherence models Group vs individual Curriculum-based vs individualized, or a mix of the two Clinic-based vs community-based organization

61 Key Points Effective adherence interventions can vary in their modality and duration, providing clinics, providers, and patients with options. Interventions shown to be effective include: nurse home visits, five-session group intervention, pager messaging, and couples based interventions. Substance abuse therapy and strengthening social support also can improve adherence. All team members: including nurses, nurse practitioners, pharmacists, medication managers, patient navigators and social workers, have integral roles in successful adherence programs. Directly observed therapy (DOT) has been shown to be effective in provision of ART to active drug users. However, the benefits are not sustained after transitioning out of the methadone clinic and halting DOT.

62 What is the most unusual task Ed has had to do as part of his research? A- Pretend to be a Man that has Sex with other Men, and answer questions about his sexual practices? B- Personally test different lubricants used for sexual activity? C- Buy vibradors from the local sex shop? D- Provide pornography to his research volunteers?

63 Case #5 62 year old man was recently diagnosed with HIV infection during routine testing He is referred to the HIV clinic for management Other Co-morbidities Hypertension Hepatitis C Diabetes Renal insufficiency

64 HIV Treatment then and Now ARV + Prophylaxis for OIs ARVs + treatment for the two, three or four co-morbidities

65 Maximizing Adherence ARV selection using clinical information, discussion of the patient s preferences Cost (co-payment) for drugs needs to be considered Selection must include knowledge of the potential drug interactions Engage the adherence team or individual in the practice to support the patient Assess adherence at EVERY visit

66 Provider Guidance for Linking Patients to Antiretroviral Therapy Adherence Interventions General recommendations on entry to care and ART adherence Obtaining self-reported adherence Self-reported low-adherence is likely to have high accuracy Self-reported high adherence offers less confidence in accuracy Journal of the International Association of Providers of AIDS Care (JIAPAC) : 79

67 Copyright by SAGE Publications Zuniga J M, and Young B J Int Assoc Provid AIDS Care 2013;12:15-17

68 Effective Interventions Dec 2010 CDC published a new online Medication Adherence chapter of the Compendium of Evidence-Based HIV Behavioral Interventions that include 8 medication adherence behavioral interventions identified from the scientific literature published. ma-good-evidence-interventions.htm

69 Thanks to our Families who support us and the work we do!