Transcript Section two
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 • 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 For the Primary HIV Clinician: Too Much to Do, Too Many Questions • 20 HIV prevention • Housing, nutrition • Family & reproductive counseling • • • • Chemical dependency Co-morbidities: Hepatitis C • • • • • • • Adherence When to start, with what? When to change? Drug toxicities Rx of experienced pts Resistance testing Immune reconstitution O.I. prophylaxis Goals of ARV therapy – HHS Guidelines 1/00 R. Sherer AETC NRC Training Slide The Extent of Non-Adherence • Diabetes - 40-50%. • Asthma - 20%. • Epilepsy - 30-40%. • Transplant - 18%. • Hypertension - 40%. • Oral contraception - 8%. Non-Adherence Rates by Medication Type • Antiarrythmics - 76% • Antihypertensives - 47% • Chemotherapy - 73% • Lipid lowering agent - 43% • Antibiotics - 67% • Anticonvulsants - 24% • Antiasthmatics - 54% • Immunosuppresants - 18% 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 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 Behavioral Correlates of Adherence ICoNA, JAIDS 2002 Demographic Age Education < 8 years Undetectable Viral Load Side effects Adherent n=298 Non adherent n=67 37.4 34.4 .001 55.2% 70.1% .025 68.0% 40.4% .001 38.9% 50.0% .001 26.5% .001 22.1% .001 Non injection 5.4% drug use Current IV drug 4.7% use p value Physician Estimate vs Measured Adherence Study Paterson Haubrich Ann Int med AIDS 1999 2002 Miller Bangsberg AdiCONA Wagner Retrovirus, 1999 JAIDS 2001 Athens, 2001 J Clin Epi 2001 Enrollment N=81 N=173 N=73 N=45 N=320 N=793 Measure of MEMS adherence Patient report MEMS Un Patient announced report pill count Patient report Dis41% cordance of estimates 45% 41% 40% 39% 34% 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 What Degree of Adherence Is Needed? Weeks 40–52 HIV RNA* vs baseline HIV RNA NVP + ddI + AZT 1.5 HIV RNA change from baseline (log10 copies/mL) 1.0 Adherent Nonadherent 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 *Lower limit = 20 copies/mL. Source: Montaner, et al. JAMA 1998;279:930. 3 4 5 6 Baseline HIV RNA (log10 copies/mL) 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, % 100 80 60 40 20 0 <70 70–80 80–90 90–95 >95 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 Proportion of subjects with sustained virologic success* (%) INCAS (AZT/ddI/NVP) AVANTI-2 (AZT/3TC/IDV) 100 80 60 40 20 0 0 8 16 24 32 40 AVANTI-3 (AZT/3TC/NFV) 100 48 0 8 Viral load Nadir 20 copies/ml 21–400 copies/ml >400 copies/ml 16 26 32 40 48 40 48 All trials combined 80 60 40 20 0 0 8 16 24 32 Weeks *HIV-1 RNA <1000 copies/ml Montaner J. 12th World AIDS Conference Geneva 1998 40 48 0 8 16 24 32 Weeks 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