1. Adherence to HAART

2. Adherence Summary Adherence is the Achilles Heel of HAART Adherence requires education, a shared negotiation, & the optimal regimen for the individual patient Simplify the regimen, BID or better, and anticipate, inform, and treat common side effects as part of adherence readiness Access to trusted, knowledgeable MD & health care team is essential G Friedland and the CORE AETC NRC Training Slide

3. For the Primary HIV Clinician: Too Much to Do, Too Many Questions 2 0 HIV prevention Housing, nutrition Family & reproductive counseling Chemical dependency Co-morbidities: Hepatitis C O.I. prophylaxis Goals of ARV therapy –HHS Guidelines 1/00 Adherence When to start, with what? When to change? Drug toxicities Rx of experienced pts Resistance testing Immune reconstitution AETC NRC Training Slide R. Sherer

4. The Extent of Non-Adherence Diabetes - 40-50%. Epilepsy - 30-40%. Hypertension - 40%. Asthma - 20%. Transplant - 18%. Oral contraception - 8%.

5. Non-Adherence Rates by Medication Type Antiarrythmics - 76% Chemotherapy - 73% Antibiotics - 67% Antiasthmatics - 54% Antihypertensives - 47% Lipid lowering agent - 43% Anticonvulsants - 24% Immunosuppresants - 18%

6. Prescriptions 1.8 Billion prescriptions annually. Over half of all prescriptions are taken incorrectly. 21% never get their prescriptions refilled. 11% of all hospital admissions are due to patients improperly taking their drugs

7. Factors that Influence Adherence Consistently predictive of non adherence –Symptoms and side effects –Negative life events/stress –Complexity of regimen Consistently predictive of adherence –Family or social support –Self-efficacy Ammassari,JAIDS 2002

8. Factors that Influence Adherence Inconsistently predictive of adherence or non adherence –Age, race, Income –Unstable housing –Active injection drug use –Alcohol consumption –Depression –Psychiatric co-morbidity –Health related quality of life –CD4 cell count –Dosing frequency –Knowledge and beliefs about treatment –Patient satisfaction with healthcare/patient-provider relationship Ammassari, JAIDS 2002

9. Factors that Influence Adherence Factors not predictive of adherence or non adherence –Gender –Education –Living with others/children –Unemployment –Medical insurance –Risk factor for HIV –History of injection drug use –Length of HIV infection –CDC disease stage –Naïve to ART –Number of antiretrovirals –Type of ARV drugs –Number of pills Ammassari, JAIDS 2002

10. Adherence in IVDUs Bouhnik, JAIDS, 2002 Ex IVDU not in drug treatment N=114 –25% non adherence –14.9% high social instability –37.7% medium social instability –47.4% low social instability Current IVDU /in drug treatment N=96 –36% non adherence –31.3% high social instability –55.2% medium social instability –13.5 low social instability

11. Behavioral Correlates of Adherence ICoNA, JAIDS 2002 DemographicAdherent n=298Non adherent n=67 p value Age37.434.4.001 Education < 8 years 55.2%70.1%.025 Undetectable Viral Load 68.0%40.4%.001 Side effects38.9%50.0%.001 Non injection drug use 5.4%26.5%.001 Current IV drug use 4.7%22.1%.001

12. Physician Estimate vs Measured Adherence StudyPaterson Ann Int med 2002 Haubrich AIDS 1999 Miller Retrovirus, 1999 Bangsberg JAIDS 2001 AdiCONA Athens, 2001 Wagner J Clin Epi 2001 EnrollmentN=81N=173N=73N=45N=320N=793 Measure of adherence MEMSPatient report MEMS Un - announced pill count Patient report Dis- cordance of estimates 41%45%41%40%34%39%

13. Adherence and HAART NNRTI vs PI based regimens –51% non adherence - PI –38% non adherence –NNRTI –41% lower risk of non adherence with NNRTI Compared with PI regimen –OR 0.53 Efavirenz non adherence –OR 0.63 Nevirapine non adherence AdICoNA and AdeSpall studies, JAIDS 2002

14. Weeks 40–52 HIV RNA* vs baseline HIV RNA *Lower limit = 20 copies/mL. Source: Montaner, et al. JAMA 1998;279:930. Baseline HIV RNA (log 10 copies/mL) NVP + ddI + AZT Adherent Nonadherent -5.0 -4.5 -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -0.5 0.0 0.5 1.0 1.5 23456 HIV RNA change from baseline (log 10 copies/mL) What Degree of Adherence Is Needed? AETC NRC Training Slide

15. Adherence to a PI-containing regimen correlates with HIV RNA response at 3 months Patients with HIV RNA <400 copies/mL, % PI adherence, % (MEMScaps) Source: Peterson, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago, IL. Abstract 92. What Degree of Adherence Is Needed? AETC NRC Training Slide

16. Several trials indicate the need to achieve better viral suppression, i.e. < 50 cps/ml AVANTI-2 (AZT/3TC/IDV)INCAS (AZT/ddI/NVP) 484032261680 100 0 20 40 60 80 081624324048 081624324048 All trials combined Weeks 0 081624324048 20 40 60 80 100 AVANTI-3 (AZT/3TC/NFV) Weeks Proportion of subjects with sustained virologic success* (%) Viral load Nadir 20 copies/ml 21–400 copies/ml >400 copies/ml *HIV-1 RNA <1000 copies/ml Montaner J. 12th World AIDS Conference Geneva 1998 AETC NRC Training Slide

17. Cochrane Review of Adherence Interventions Adherence interventions for all types of diseases Limited to Randomized Controlled Trials without confounding Two HAART trials fit the criteria for inclusion Many HAART trials excluded due to: –Limited follow-up time –Confounding –Missing data –Significant lost to follow up –Adherence intervention unclear –Lack of a control group

18. Cochrane Reviewed HAART Adherence Interventions Knobel, Enferm Infecc Microbiol Clin 1999 Study design –ZDV+ Lamivudine + Indinavir + conventional care –ZDV + Lamivudine+ Indinavir + counselling and adaptation of treatment to patient lifestyle, telephone support, detailed medication information –Adherence measured by pill count, structured interview –Compliance = 90% drugs taken > 90% meds taken according to schedule < 2 mistakes in pill intake /day Study impact –Positive effect on adherence –Reduced viral load

19. Cochrane Review of Adherence Interventions Tuldra, JAIDS 2000 Study Design –Usual medical follow up vs education Psycho educative intervention to implement adherence Dosing schedule with patients’ input Phone support Study Impact –No effect on adherence –No effect on outcome

20. Limitations of HAART Adherence Studies Lack of reliable measurements of adherence Lack of consistent measurements across studies Assessment of adherence predictors Small sample size Variation in study design Ability to generalize study design Applicability of other chronic disease studies to HIV Wide variation in reported results Limited time of follow up assessments JAIDS, 2002

21. Adherence works best when: Relationship between patient and provider is based on trust Patient has adequate support Multidisciplinary healthcare team Multidisciplinary client centered approach Approach individually tailored to patient’s needs Adherence is a process, not a single event