Adherence Preparing to start ARVs Dr. Kevin M Harvey MBBS, MPH (UWI), Dip. ID (Lon.) Treatment care and support 2006

What do we know?:HIV Treatment in 2004 Many regimens are active in people with no drug resistance –Measured as suppression of virus (lowering plasma viral load to under detection) or other response to treatment (CD4, clinical, weight etc) But treatment after resistance develops is still a challenge and usually requires more complicated and/or more expensive regimens In addition resistant virus can be transmitted Failure carries a high price on an individual, financial and public health Finding the reasons and preventing failure is therefor critical

Why does antiretroviral therapy fail? Not a cure Efficacy Drug toxicity Drug interactions Drug resistance Adherence issues – lifelong therapy Cost

Failure of Therapy: Types of failure Clinical failure Progression of disease, new infections Immunologic failure Decline in CD4 count Virologic failure Persistent viral replication (usually associated with resistance) Drug toxicity Severe side effects Infrastructure failure Lack of drug supply, lack of money to pay for drugs

ART in the “Real” World Many clinical trials show suppression of virus in >80% of subjects BUT, studies in a multitude of clinical settings have shown only 50-70% success rates with multiple-drug therapy at 1-2 years WHY? While baseline resistance and poor prescribing contribute, poor adherence accounts for many of these failures* As HIV turns from a uniformly fatal illness to a chronic disease, adherence grows even more important *Estimates from 40-80% report some non-adherence

Adherence Compliance Concordance Taking the medication/following the regimen as directed (dose, timing, diet etc etc) with follow-up and care as directed WHO: the extent to which a person’s behaviour – taking medication, following a diet,and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider.

Adherence in other diseases* Poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude –Average of 50% in most diseases –Ex. Non-adherence accounts for a significant percent of admissions in patients with heart failure The consequences of poor adherence to long-term therapies are poor health outcomes and increased health care costs Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments A multidisciplinary approach towards adherence is needed *WHO. Adherence to long-term therapies: evidence for action, 2003.

Adherence is simultaneously influenced by several factors Factors include: –Medication Ex. Dose frequency, side effects –Patient ex. Readiness, substance use –Health care system/providers Ex. Patient provider relationship Treatment education DOT cost –Community/environment Ex. Stigma, transport Adherence is a dynamic process that needs to be followed up –Improving long-term adherence is complex and required continuous support and monitoring Health professionals need to be trained in adherence Family, community and patients’ organizations: a key factor for success in improving adherence WHO. Adherence to long-term therapies: evidence for action

Why is HIV different Excellent adherence in other diseases is considered >60-70% Adherence rates for HIV need to be higher –>95% Non adherence with HIV carries very high risk of virus developing drug resistance Once resistance develops, that drug (and possibly others) will never work as well or may not work at all Communicable disease

Adherence and viral suppression Haubrich RH, et al. AIDS 1999;13: Months6 Months Percentage of Medication Taken <80% 80% to 95%95% to 99% 100 % Percent of patients with viral load <500 copies

HIV, adherence and clinical significance Better adherence is also linked with decreased risk of getter sicker from HIV infection, losing more CD4 cells, and dying from HIV

Adherence in resource richer areas Average rates of adherence vary widely, but generally fall well short Percentage of patients with treatment failure in clinical practice reflect a combination of non adherence and resistance: –USA50% –Amsterdam40% –Swiss naïve38% experienced70% –Johns Hopkins63% –Cleveland53%

Adherence to ARVs treatment over time *p<0.01 for difference between months 1 & 4 and months 1 & 8 Mannheimer et al, CPCRA, Percent reporting 100% adherence

Adherence in Resource-limited settings In programs with self-pay, cost is not always the major barrier to adherence Innovative approaches to support adherence before and during treatment are being used

Adherence to ARVs in resource-limited settings:* –Uganda: 88% –Cote d’Ivoire: 75% –Haiti: 88% –Senegal: 78%-88% –South Africa: 89% –Brazil: range: 57%-87% –Botswana: ~55% –Nigeria: 58% –Kenya: 59% Adherence is as problematic in resource-limited settings as it is in resource-rich settings. No evidence to show that it is more problematic. * NB: small studies, differing definitions of adherence

Adherence in resource limited settings African Countries Strong pre treatment education and screening, counselors and treatment buddy High rates of adherence, viral suppression Need to determine critical components for scale-up Cootzee, AIDS 18 suppl 3, 2004

Predictors of nonadherence: Medication related dosing frequency side effects Number of pills ?type of medication ?complexity of regimen

Patient-related Active substance abuse Depression HIV knowledge and knowledge and belief in medications Literacy (?more of a system problem) Non-adherence to care Stage of readiness ?Distance from site ?age ?disclosure

System-related Cost of care/treatment Access to care and medications provider/patient relationship Stock-outs ?employment out of the home ?transportation ?stigma

Non-predictors Non-predictors include –Race –gender –prior substance abuse –social status or income –education

Other reasons people do not take their ART Pill fatigue Forgot Pills not with them Transportation Fear of disclosure Concern with drug interactions (prescribed or other) And others

Preparing for Adherence More sustainable response to ARVs if adherence is optimized within the first three to six months Must therefore prepare individuals to adhere prior to the start of ARVS Must also have a strategy to sustain adherence throughout life

Preparing for ARVs Culture Access +Knowledge + Motivation+Cues to Action Stigma & Discrimination ADHERENCE

Access Potential Barriers Distance from Clinic Appointment system User Fees Availability of Service Confidentiality Stigma & Discrimination Cost for CD4,Viral Loads + other labs Cost of other Medicines Cultural Practices Possible Solutions Telephone Appointments Waiver from User Fees (free does not =Access) Waiver from General fees & lab cost via assessment Process Refer closest acceptable Treatment site Assistant with Bus Fares Register with the NHF Family support

Knowledge Potential Barriers Believes Culture Myths Low literacy Lack of Exposure to Specific HIV Education Educational Material inappropriate Possible Solutions Appropriate Literacy Material for Individual HIV Basic Facts Condom Negotiation Skills Name etc of Specific Meds

Motivation Potential Barriers –Depression –Number of pills –Frequency of doses per day –No Family support –No disclosure /fear disclosure –Negligence/ forgetfulness –Unemployment –Lack of privacy Possible Solutions –Refer to Social Worker –Mental Health Professional –Reduce the number of pills If possible link meds to something the patient does that they enjoy –Refer to support groups –Encourage disclosure, –provide temporary support –encourage buddy system –Channel to income generating projects

Cues to Action Barriers Non Disclosure and lack of support Drug addiction Stigma and Discrimination Attention drawn by Reminders Pill boxes can be too big Late refills Cognitive function Possible Solutions Family Support Media Pill Boxes Text Messages Alarms Link to Favourite radio and TV programmes Support at workplace

Culture Barriers Patients only listen to doctor Alternative Medicine Can provide a Cure Role of the Church Myths Solutions Patients will listen to Doctors Alternative(Herbal Medicines) can be immune boosters Education of Clergy

Stigma & Discrimination Potential Barriers Fear Discrimination Lack of or Low Public education Remove Labels Fail to take meds in Public Move away from district Do not want to attend Clinic in Own district Visible side effects Possible Solutions –Confidentiality at the work place is key –Reduced stigma and discrimination at work place –Refer to acceptable treatment site or facilitate easier access

Supportive Environment Knowledge Motivation Positive Behaviour Change Increased Adherence

Family-Focused Adherence Support It may take several weeks and several visits to ready the family for treatment. Before prescribing –Family is part of and agrees with treatment plan –Assess family life-style, priorities, beliefs –Ask about prior medication experience: build on success and work on problems –Educate about the disease, purpose of ARV, importance of adherence –Repeat information as many times as necessary

Family-Focused Adherence Support Planning for a good start: –Develop a simple schedule that fits the family’s daily activities. Consider differences between weekdays and weekends. –Clarify who will be responsible for giving or supervising each dose, each day of the week –Make the schedule visual. Use pictures of pills. Color- code everything. Consider literacy level of family members

Family-Focused Adherence Support Planning for a good start: –Demonstrate medication preparation: measuring volumes of liquids crushing or dissolving tablets opening capsules using foods or liquids to mask task –Do a trial run with “dummy” pills or liquid –Observe medication administration in the office. If possible, start the first dose under supervision –Follow-up with a phone call and/or home visit in the first few days

General lessons we have learned Adherence is hard for everyone and long term treatment present the most difficult challenges Adherence is critical to the successful care of patients with HIV/AIDS –On an individual level, adherence to care and treatment can mean the difference between life and death –On a population level, adherence to treatment can minimize the emergence of viral resistance and prevent therapeutic failure Adherence needs to be to medications and care.

More lessons Every HIV/AIDS treatment program should include processes to assess and support adherence Adherence promotion must be multifaceted and multidisciplinary and adapt to changing needs and realities –Many models/approaches in use –Many also need to be evaluated and adapted for local needs Simpler and more tolerable regimens which preserve efficacy are still needed

Acknowledgements Sources for some of the slides or materials included: –KITSO AIDS Training Program (Botswana) –MTCT-Plus training (Columbia University) –Vietnam-CDC-Harvard Medical School AIDS Partnership (VCHAP) –Colleagues and most importantly,people living with HIV