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Adherence to HAART. Adherence Summary. Adherence is the Achilles Heel of HAART Adherence requires education, a shared negotiation, & the optimal regimen for the individual patient
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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
20 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 For the Primary HIV Clinician: Too Much to Do, Too Many Questions AETC NRC Training Slide R. Sherer
Diabetes - 40-50%. Epilepsy - 30-40%. Hypertension - 40%. Asthma - 20%. Transplant - 18%. Oral contraception - 8%. The Extent of Non-Adherence
Antiarrythmics - 76% Chemotherapy - 73% Antibiotics - 67% Antiasthmatics - 54% Antihypertensives - 47% Lipid lowering agent - 43% Anticonvulsants - 24% Immunosuppresants - 18% Non-Adherence Rates by Medication Type
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
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
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
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
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 Adherence in IVDUsBouhnik, JAIDS, 2002
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
1.5 1.0 0.5 0.0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0 -4.5 -5.0 2 3 4 5 6 What Degree of Adherence Is Needed? Weeks 40–52 HIV RNA* vs baseline HIV RNA NVP + ddI + AZT Adherent Nonadherent HIV RNAchange from baseline(log10 copies/mL) Baseline HIV RNA(log10 copies/mL) *Lower limit = 20 copies/mL. Source: Montaner, et al. JAMA 1998;279:930. AETC NRC Training Slide
What Degree of Adherence Is Needed? 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. AETC NRC Training Slide
Several trials indicate the need to achieve better viral suppression, i.e. < 50 cps/ml INCAS (AZT/ddI/NVP) AVANTI-2 (AZT/3TC/IDV) 100 80 60 40 20 0 0 8 16 24 32 40 48 0 8 16 26 32 40 48 Viral load Nadir 20 copies/ml 21–400 copies/ml >400 copies/ml Proportion of subjects with sustained virologic success* (%) AVANTI-3 (AZT/3TC/NFV) All trials combined 100 80 60 40 20 0 0 8 16 24 32 40 48 0 8 16 24 32 40 48 Weeks Weeks *HIV-1 RNA <1000 copies/ml Montaner J. 12th World AIDS Conference Geneva 1998 AETC NRC Training Slide
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
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
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
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
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