Catherine Sarai Racey March 19 th 2009 MPH Capstone Defense

1. Patient Comprehension of Antiretroviral Drug Resistance:Implications for Treatment and Clinical Practice Catherine Sarai Racey March 19th 2009 MPH Capstone Defense

2. BC Centre for Excellence in HIV/AIDS • The B.C. Centre for Excellence in HIV/AIDS (CfE) is Canada’s largest HIV/AIDS research and treatment facility. • The Centre was founded by St. Paul’s Hospital and the provincial Ministry of Health and is dedicated to improving the health of British Columbians with HIV. • In B.C., all anti-HIV medications are distributed at no cost to eligible HIV-infected individuals through the Centre’s Drug Treatment Program. • As of the last update nearly 4,380 HIV-positive persons are accessing therapy in the province. • Approximately 54 new patients access therapy each month. (www.cfenet.ubc.ca)

3. Health Literacy • Vital component for chronic disease care • Encompasses: • the capacity to act on knowledge • understand treatment and health risks • ability to utilize the health care system • A key element of self-management is health literacy • Poor health literacy is associated with poor health outcomes • A component of high health literacy is understanding treatment

4. HIV/AIDS Treatment • Dramatic reduced morbidity and mortality • High level of adherence in order to maximize benefits • Incomplete adherence is a key determinant in the development of drug resistance • Antiretroviral drug resistance is: • a significant reduction of drug efficacy due to mutations in the viral genome. Drug resistant quasi-species can emerge and be selected when the viral population is exposed to sub-optimal drug levels13 • Antiviral drug resistance limits treatment options • Differential adherence and drug resistance have been associated with an increased risk of death

5. Importance of Health Care Providers • The health care provider plays an important role • The relationship is an important factor in treatment success, including better adherence • Positive relationships provide opportunities • Physician experience associated with improved survival and perception of care • Pharmacists play an important role in adherence counseling and daily treatment concerns

6. HIV/AIDS Health Literacy • Self-management strategies minimize symptoms in HIV patients • Knowledgeable about HIV/AIDS, as well as overall treatment plans • Key focus in treatment is preventing and prolonging development of HIV drug resistance • Patients need to understand fully the nature of their treatment, the implications of incomplete adherence and the consequences of developing drug resistance

7. Objective • To determine the current level of Knowledge of HIV drug resistance in a cohort of HIV+ people on HAART • Identify predictive factors for comprehension • Identify areas of focus for improving comprehension

8. Methods • The LISA project is conducted through the Drug Treatment Program (DTP) at the CfE • LISA is a 3 – year prospective cohort, which aims to examine the effects of various supportive health services on the health status of HIV+ persons on meds • Eligibility: HIV+, 18+years and on medication after 1996 • Participants were recruited through physician letters and advertisements at local HIV/AIDS service organizations • A 45 minute comprehensive interviewer-administered survey • On-going linkage with the DTP provided data on the clinical variables

9. Instrument – Variables • Physician – patient relationship • length of time with physician, if they choose or were referred, ever switched physicians and if they are satisfied with care • Pharmacist involvement • ever received one-to-one counseling by a pharmacist when beginning or switching medications • Quality of life • using a 9-item HIV/AIDS – targeted quality of life scale18 • Housing stability • assessed with stable or non-stable housing • Food security • 13-item Radimer/Cornell measurement scale19 • Other socio-demographic variables • ever or current illicit drug use, current employment, provincial income assistance and level of education • Adherence • refill adherence, measured as the number of days medication is dispensed divided by the number of days medication is prescribed (<95% and ≥95% adherence)

10. Resistance knowledge variable • Knowledge of HIV drug resistance was conducted through a 2 – part question • A complete definition had to identify: • Importance of adherence • Presence of a viral mutation (or change) • Drugs ceasing to work • Coding: • Identify 3 factors – complete • Identify 1 – 2 factors – partial • Identify 0 factors – incorrect • Responses of ‘unsure’, ‘don’t know’, or blank were coded as no response

11. Statistical Analysis • In the multivariable analysis ‘complete’ and ‘partial’ definitions were pooled and ‘no response’ and ‘incorrect’ were pooled. • Three comparison groups • Bivariable analysis investigated associations using Fisher’s Exact test or the Chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables • Logistic regression was used for unadjusted bivariable and the adjusted multivariable analysis

12. Results • As of July 2008 there were 457 participants • 90% are currently on HAART • The median age is 46, with 75% being male • At the time if interview 46% of participants had CD4 cell counts of ≥350 cells/mm3 and 58% were virologically suppressed • 45% of the cohort was ≥95% adherent • 23% reported gainful employment and 47% reported using illicit drugs (heroin, cocaine, crack, speedball, crystal meth) • 94% reported being highly satisfied with their physician and over 80% reported high provider trust

18. Results – Bivariable Analysis • Based on Bivariable model participants who gave partial or complete definitions more likely to:

19. Results – Resistance Knowledge • Based on multivariable model participants who gave partial or complete definitions more likely to:

20. Results – Resistance Knowledge • Based on multivariable model participants who gave partial or complete definitions more likely to:

21. Results – Resistance Knowledge • Based on multivariable model participants who gave partial or complete definitions more likely to:

22. The probability of a complete or partial definition increased from 15.90% (without discussing medications with a physician or receiving one-to-one counseling by a pharmacist) to 63.90% (if a participant received both)

23. Limitations • Use of participant reported definitions • The working definition is stringent with complete definitions having to identify all 3 factors • Subsequently controlled for in the analysis by pooling. Participants who were able to identify 1 to 3 of the factors were pooled. • Distribution of participants • As of July 1st ½ the LISA cohort reported current illicit drug use and over 45% of interviews were conducted at one site • As the number of interview sites increases the make-up of the cohort will become more representative of the HIV population in BC

24. Conclusions • HIV drug resistance knowledge is low • Participants who were able to completely or partially define resistance had: higher provider trust, higher education, were on average younger, discussed medications with their physician and had one-to-one counseling session with a pharmacist. • Two areas of focus for interventions are: discussing medications with physicians and one-to-one counseling with a pharmacist • Health literacy has been demonstrated as an important factor in treating chronic diseases • Building health literacy capacity through increased knowledge of HIV drug resistance may help close the gap between adherence and improve clinical outcomes • Clinically relevant universal guidelines for patient education may help direct consistent discussions and information for patients

25. Future Directions • There are no provincial guidelines for patient education • Devising a standardized patient education package which incorporates the major mechanisms for developing resistance, the implications for treatment and quality of life and the importance of adherence • A clinically relevant example: The IDC • The program will comprise of a series of workshops whose objectives tackle different areas of patient education • Including: access to special health care services and preventing and prolonging drug resistance • The workshops will be delivered over a period of time in hopes of engaging patients • Engaged patients, with better health literacy, will do better in self-management

26. Dissemination • Accepted Poster presentation at Ontario HIV Treatment Network (OHTN) 2008 Conference – November 13-14th 2008 • Accepted Oral presentation at the Canadian Association for HIV Research (CAHR) 2009 Conference – April 23-26th 2009 • To be submitted for peer review in the Journal - AIDS

27. Acknowledgements • I would like to acknowledge all of the LISA participants. • Forever grateful to Wendy Zhang, Kimberly Fernendes, Eirikka Brandson, Despina Tzemis, Richard Harrigan, Julio Montaner, Junine Toy, Rolando Barrios and Bob Hogg for their contributions and guidance. • Thank you to the LISA team:Alexis Palmer, Katie Duncan, Andy Mtambo, Oghenowede Eyawo, Despina Tzemis, Alexandra Borwein, Mark Philips and Elizabeth Pipes. • Special thank you to Eirikka Brandson, for her mentorship and encouragement, Rolando Barrios for his insight and support, and Bob Hogg for the wonderful opportunity to be a part of the LISA team and for providing excellent guidance and support throughout.

28. Bibliography Wood E, Montaner JSG, Yip B, Tyndall MW, Schechter MT, O'Shaughnessy MV, et al. Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users. CMAJ 2003; 169:656-661. Stone VE. Strategies for Optimizing Adherence to Highly Active Antiretroviral Therapy: Lessons from Research and Clinical Practice. CID 2001; 33:865-872. Moore DM, Hogg RS, Yip B, Craib K, Wood E, Montaner JSG. CD4 percentage is an independent predictor of survival in patients starting antiretroviral therapy with absolute CD4 cell counts between 200 and 350 cells/microL. HIV Med 2006; 7:383-388. Montaner JS, Hogg RS, Heath KV, Phillips P, Craib KJ, Schechter MT, et al. Heterogeneity of physician agreement with recommended therapeutic guidelines for the management of HIV-associated disease. Antivir Ther 1996; 1:157-166. Moore DM, Hogg RS, Yip B, Craib K, Wood E, Montaner JSG. CD4 percentage is an independent predictor of survival in patients starting antiretroviral therapy with absolute CD4 cell counts between 200 and 350 cells/microL. HIV Med 2006; 7:383-388. Stone VE, Hogan JW, Schuman P, Rompalo AM, Howard AA, Korkontzelou C, et al. Antiretroviral Regimen Complexity, Self-Reported Adherence, and HIV Patients' Understanding of Their Regimens: Survey of Women in the HER Study. JAIDS: Journal of Acquired Immune Deficiency Syndromes 2001; 28:124. Sungkanuparph S, Groger RK, Overton ET, Fraser VJ, Powderly WG. Persistent low-level viraemia and virological failure in HIV-1-infected patients treated with highly active antiretroviral therapy. HIV Medicine 2006; 7:437-441. Tuldrà A, Wu AW. Interventions to improve adherence to antiretroviral therapy. J Acquir Immune Defic Syndr 2002; 31 Suppl 3:S154-7. Battaglioli-DeNero AM. Strategies for improving patient adherence to therapy and long-term patient outcomes. J Assoc Nurses AIDS Care 2007; 18:S17-22. March K, Mak M, Louie SG. Effects of pharmacists' interventions on patient outcomes in an HIV primary care clinic. American Journal of Health-System Pharmacy 2007; 64:2574-2578.