Adherence

Pharmacotherapy Services/Adherence

Recent Publications Study Finds Intensive Coaching Improves Antiretroviral Therapy Adherence Intensive Adherence Interventions Improve Virologic Response to Antiretroviral Therapy (ART) in Treatment Naïve Patients Issues in HIV Pharmacotherapy Practice: The Emerging Role of Pharmacotherapy Specialists in Enhancing Antiretroviral Success Intensive Adherence Interventions Improve Virologic Response to Antiretroviral Therapy in Treatment Naive Patients [PDF] The Development of HIV Adherence/Pharmacotherapy Service in Urban Ambulatory HIV Clinic [PDF] Other Related Links Treatment Guidelines HAART and Adherence [Medscape] Patient Care Tools Antiretroviral Quick Guide Patient Information for antiretrovirals Online Printable Forms Pediatric Baseline Adherence Assessment Form Pediatric Intake/Satisfaction Questionnaire Pharmacist Adherence Assessment Form HIV Medical Progress Note HIV Pharmacotherapy Progress Note Inpatient HIV Continuity of Care Form Multidisciplinary Virology Conference Template

Linda M. Catanzaro, Pharm.D.

Clinical Assistant Professor
Department of Pharmacy Practice
School of Pharmacy and Pharmaceutical Sciences
University at Buffalo
HIV Pharmaceutical Care Specialist
Adherence-Pharmacology Unit Coordinator
Erie County Medical Center
Email: lburow@buffalo.edu

Information for this section originally compiled by Dr. Lori Esch, PharmD

Summary

Treatment of HIV disease has changed dramatically with the availability of more antiretroviral agents than ever before. Unfortunately, results from well designed trials and use of potent, strategic antiretroviral regimens are fruitless if the prescribed medications are not being taken by the patient, exactly as intended. The challenge of optimizing adherence to antiretrovirals remains paramount in the treatment of HIV. The dire importance of this challenge is clearer with recent data suggesting that greater than 95% adherence to antiretroviral medications is required to achieve satisfactory viral suppression¹. Among patients with 80% to 90% adherence, the 50% failure rate is in the range now seen in most trials and in clinical practice^1,2. Innovative changes in clinical practice models have been proposed and implemented by some to try to incorporate multiple disciplines into optimal patient management^3,4.

FACTORS CONTRIBUTING TO NON-ADHERENCE

Many factors exist that can serve to reduce patient adherence to therapy and successful adherence interventions involve providing support in areas required specific to each patient. Since adherence is affected by a combination of factors, all must be assessed and addressed to optimize disease outcomes and avoid the ultimate consequence of non-adherence, drug failure. Patient-related issues, drug-related issues and issues relating to patient-provider communication can influence adherence. Failure to recognize and address these issues may result in discordance between priorities of patients versus caregivers and subsequent inability to help improve adherence with appropriate measures⁵.

ASSESSMENT OF ADHERENCE

Strategies to measure adherence are still comparable to the quest for the holy grail. Attempts to quantify adherence for the purposes of correlating it to predictors as well as outcomes, has been fraught with complications. Self-reported adherence by the patient has been shown to correlate with virologic outcomes^6,7, however, it has also been shown to underestimate adherence measured by electronic means (eg. MEMScaps) which have also been shown to correlate with virologic outcomes^1,8. Other methods, such as pill count and refill history are beneficial, but on their own, do not provide accurate adherence assessments. As patient-reported means is still the most common and most accessible method to assess true adherence, it is necessary to examine how questions are being posed to patients and how caregivers are collecting information regarding patient-reported adherence.

INTEGRATION OF ADHERENCE ASSESSMENT WITH PHARMACOLOGIC FACTORS

Although challenging, the ability to assess and document adherence is critical in a number of clinical scenarios. With the difficulty of salvaging or rescuing patients who have failed previous antiretroviral regimens, it is desirable to accurately address and hopefully correct factors which contribute to virologic escape. Non-adherence is a key factor contributing to failure of antiretrovirals and needs to be appreciated and addressed prior to instituting a change in therapy.

Recent interest has emerged in genotypic and phenotypic resistance testing, both, both of which can be valuable tools to assist in optimal drug selection. It is necessary, however, to have an accurate assessment of patient adherence prior to interpreting the results of these tests. Additionally, a potential role for drug concentration monitoring of antiretrovirals is currently being explored. There are still many obstacles remaining to determining the exact role of these concentrations and how they should be interpreted. It is critical, however, to have an accurate assessment of patients' adherence to the prescribed antiretroviral regimens and concurrent medications in order to assist in interpreting the appropriateness of the concentrations.

PRACTICE CHANGE AND EMERGING MODELS OF CARE

New practice models are required to assist patients in achieving sufficient adherence for reaching undetectable viral loads. HIV pharmacotherapy specialists are in a unique position to impact virologic outcomes in antiretroviral therapy, assessing adherence, potential drug-related toxicities and drug-drug or drug-food interactions, all factors tantamount to ensuring antiviral success. The interface of antiretroviral pharmacokinetics and pharmacodynamics are critical to optimizing therapeutic regimens and can be addressed by pharmacotherapists with expertise.

Programs are beginning to surface which provide integrated innovative models for integrating patient adherence assessment with pharmacokinetic, pharmacodynamic and virologic outcome analysis^3,4,9. Preliminary evidence suggests that interventions by HIV pharmacotherapists can improve the virologic outcomes in patients on antiretroviral therapy.

The progression in antiretroviral therapy to complex, chronic regimens has made pharmacologic assessment of the patient an important aspect of chronic HIV management. HIV pharmacotherapists can be highly qualified to evaluate patients with complex drug regimens who are facing barriers to successful care, target the appropriate intervention(s), and follow-up with the patients on a long-term basis. Emerging models demonstrating the expertise of pharmacotherapy specialists may show that a great deal more than choosing potent antiretrovirals is need to ensure desired outcomes.

REFERENCES

1. Paterson D, Swindels S, Mohr J, et al. How much adherence is enough? A prospective study of adherence to protease inhibitor therapy using MEMSCaps. In: Program and abstracts of the Sixth Conference on Retroviruses and Opportunistic Infections; January 31-February 4, 1999; Chicago. Abstract 92.

2. Lucas GM, Chiasson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med 1999;131:81-87. [PubMed]

3. Esch LD, Hardy H, Shelton MJ, Hewitt RG, Morse GD. Adherence as a determinant of virologic response to highly active antiretroviral therapy. Presented at the American College of Clinical Pharmacists Annual Meeting, Kansas City, Missouri, October 24-27, 1999 (abstract 232).

4. Graham K, Beeler LH, Renae S, Sension MG. Interventions and patient outcome from a pharmacist-based HIV medication adherence referral clinic. 12th Int Conf AIDS 12:585 (abstract no. 390/32323) Geneva, Switzerland, June 28-July 3, 1998.

5. Gallant JE, Block DS. Adherence to antiretroviral regimens in HIV infected patients: results of a survey among physicians and patients. J Int Assoc Phys AIDS Care 1998;4(5):32-5.

6. Shelton MJ, Esch LD, Hewitt RG et al. Correlation between self-reported adherence and virologic outcome [abstr]. Presented at the 38th Interscience Conference on Antimicrobial Agents & Chemotherapy. 1998.

7. Demasi R, Tolson J, Pham S, Capuano G, Graham N, Fisher R, Shaefer M, Eron J. Self-reported adherence to HAART and correlation with HIV RNA: initial results with the patient medication adherence questionnaire. [abstract 94] 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 1999.

8. Golin C, Lui H, Hays R, Ickovics J, Beck K, Miller L, Kaplan A, Wenger N. Self-reported adherence to protease inhibitors substantially overestimates an objective measure. [abstract 95] 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 1999.

9. Esch L, Shelton M, Esch A, Morse G, and Hewitt R. Medication adherence enhancement after viral genotyping in HIV+ patients failing highly active antiretroviral therapy (HAART). Int Conf AIDS 12:592-3 (abstract no. 32357) Geneva, Switzerland, June 28-July 3, 1998.

RECENT PUBLICATIONS

Garcia R, Ponde M, Lima M, et al. Lack of effect of motivation on the adherence of HIV-positive/AIDS patients to antiretroviral treatment. Brazilian Journal of Infectious Disease 2005;9(6):494-499.

• The authors, professors at the Federal University at Bahia and the Medical School of Bahia in Brazil, examine the effect on adherence in treatment-naïve HIV positive patients who are provided motivational sessions with social workers in addition to the basic educational assistance provided when starting antiretroviral therapy. The motivational sessions were developed based on the FRAMES model: feedback, responsibility, advice, menu of strategies, empathy, and self-efficacy. Adherence was evaluated by two means: viral load and CD4 count before and following treatment for six months. The study revealed that the group receiving motivational sessions did not have any improvement in adherence compared to the group receiving only basic educational assistance when initially beginning antiretroviral therapy. The study had a limited sample size (n=76) and the results were not conclusive. The conclusion was that providing motivational counseling may still be beneficial to improve adherence in HIV positive patients starting antiretroviral therapy.

Fletcher CV, Testa MA, Brundage RC, et al. Four measures of antiretroviral medication adherence and virologic response in AIDS clinical trials groups study 359. JAIDS 2005;40(3):301-306.

• The author, a pharmacist from the Department of Clinical Pharmacy at the University of Colorado, attempts to describe the relationship among the four adherence measures that were tested in the AIDS Clinical Trials Group (ACTG) 359. The ACTG 359 trial was a randomized, partially double-blind study of six antiretroviral regimens that evaluated adherence using counts of returned medications, patient self-report, MEMS cap and measured protease inhibitor concentrations in plasma. Upon reviewing the ACTG 359 trial, it was determined that self-reported adherence and plasma concentrations of the antiretrovirals were the only adherence measures that were correlated with a virologic response, or reduced HIV viral load. The authors concluded that this relationship between self-reported adherence and plasma drug concentrations on reduced viral load provided insight into what methods of assessing adherence were more effective than others.

Remien RH, Stirrat MJ, Dolezal C, et al. Couple-focused support to improve HIV medication adherence: a randomized controlled trial. AIDS 2005;19(8):807-814.

• The authors, faculty from the HIV Center for Clinical and Behavioral Studies at Columbia University, conducted the first couple-based antiretroviral adherence intervention to be tested in a controlled, randomized trial (the SMART Couples Study). This trial, which was held at two HIV/AIDS outpatient clinics in New York City, was designed to assess the efficacy of providing intervention and education to both members of a couple on adherence to HAART. This intervention consisted of four couple-focused adherence sessions comprised of education on adherence barriers, developing communication and problem-solving strategies, optimizing partner support, and building confidence for optimal adherence. Adherence was monitored at baseline and after eight weeks using a MEMS caps. At eight weeks, adherence was higher in patients who attended the couples intervention sessions compared to the control group who did not receive couples education. This study demonstrates the positive effect on adherence when both members of a couple are educated on the importance of HAART adherence. While this study demonstrated adherence improvement, the results were attenuated over time suggesting the need for continuing education.

Vrijens B, Goetghebeur E, deKlerk E, et al. Modeling the association between adherence and viral load in HIV-infected patients. Statistics in Medicine 2005;24(17):2719-2731.

• The authors of this study evaluated the results of a multi-centre, multi-country randomized trial involving 35 treatment-naïve HIV positive patients who received a new HAART regimen. The objective of this study was to investigate the effect of adherence to HAART on the virologic response which is frequently measured by plasma viral load. The patients evaluated had baseline plasma viral load information available in addition to follow-ups at weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48 on antiretroviral therapy. In addition to the plasma viral load measurements, adherence was monitored using a MEMS cap. Using the information from this trial, the authors were able to demonstrate a relationship between patient adherence which is electronically monitored and virologic response monitored via plasma viral load. This study supports the importance of adherence to HAART to achieving adequate virologic response.

Weaver KE, Llabre MM, Duran RE, et al. A stress and coping model of medication adherence and viral load in HIV-positive men and women on highly active antiretroviral therapy (HAART). Health Psychology 2005;24(4):385-392.

• The authors, faculty at the Department of Psychology and Behavioral Medicine Research Center at the University of Miami, examine the association between social support, coping mechanisms, and negative mood with adherence to HAART and HIV viral load. The study included 188 men and 134 women who were currently receiving HAART. Adherence to the medications was measured using self-report as well as electronic monitoring using a MEMS cap on the prescription vials. Coping strategies, negative mood, and social support were monitored with questionnaires using a rating scale. The patients were monitored at baseline, at three months, and then every 6 months for one year. The authors found that greater negative mood and less social support were directly related to coping strategies. The coping strategies were identified as avoidance-oriented and included denial and behavioral disengagement. Increased coping strategies were also directly related to poor medication adherence and higher viral load. This study emphasizes the impact of social and emotional variables on the adherence and disease progression in HIV patients.

Milan J, Richardson JL, McCutchan A, et al. Effect of brief antiretroviral adherence intervention delivered by HIV care providers. JAIDS 2005;40(3):356-363.

• The authors, faculty at the Department of Preventive Medicine at the University of Southern California, evaluated the impact on adherence of brief interventions provided to HIV positive patients by their primary care providers during routine medical appointments. Six clinics were included in the study, with two clinics offering interventions specifically on antiretroviral adherence and four clinics offering interventions regarding safer sex. The interventions were comprised of written materials, such as posters and brochures, and a brief counseling session from the medical provider. Adherence and viral load were measured before the study began and after 10 months of intervention. Adherence was measured using self-report. The study found that among the patients who had 95% or greater adherence at baseline, 91% of those who received adherence interventions remained adherent compared to 75% of those who received safer sex intervention. The results in the patients who were less than 95% adherent at baseline were not significant. The authors determined that brief interventions were successful in maintaining adherence but longer sessions or more rigorous interventions appear to be necessary to improve adherence in nonadherent patients.

Nieuwkerk PT, Oort FJ. Self-reported adherence to antiretroviral therapy for HIV-1 infection and virologic treatment response: a meta-analysis. JAIDS 2005;38(4):445-448.

• The authors, both members of the Department of Medical Psychology at the University of Amsterdam, performed a meta-analysis to evaluate whether the variability of self-reported adherence on treatment response could be directly related to the adherence measurement, study design, or study population. The authors used studies of adult HIV positive patients receiving antiretroviral therapy that used self-reported adherence measurements and provided a relationship between the adherence and HIV viral load. This evaluation determined that self-reported adherence to HAART had a significant effect on virologic response and was able to distinguish between patient adherence and nonadherence. This evaluation also found a relationship between adherence-virologic response and the number of regimens the patients had been on prior to the trial. Patients on their first antiretroviral regimen had an improved relationship between the self-reported adherence and virologic response. This study concluded that future researchers take the following precautions when using self-report for record of adherence: inquire whether or not patients are on their initial HAART regimen and use actual viral load measurement in addition to the self-report.

Yun LW, Maravi M, Kobayashi JS, et al. Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients. JAIDS 2005;38(4):432-438.

• The authors conducted a retrospective cohort study to evaluate the impact of antidepressant therapy (ADT) on adherence to antiretroviral therapy (ART). The patients included in the study were diagnosed as HIV positive and depressed, with depression being based on the DSM-IV or Major Depressive Disorder criteria. Information regarding ADT and ART was accessed via the Denver Health Clinic and adherence was determined based on pharmacy records. The impact of ADT on adherence was calculated by comparing the proportion of depressed HIV positive patients who were >95% adherent among those who were and were not prescribed antidepressants. The authors found that the rate of adherence to ART was significantly lower among depressed patients not receiving treatment for depression compared with those who had received antidepressants (p=0.01). It was also concluded that adherence to antiretrovirals was significantly higher in patients who were >95% adherent to the antidepressant therapy compared to those with poorer adherence to antidepressants (p=0.001). This study showed that diagnosis and treatment of depression in HIV positive patients may improve adherence to antiretroviral therapy.

Gonzalez JS, Penedo FJ, Antoni MH, et al. Social support, positive states of mind, and HIV treatment adherence in men and women living with HIV/AIDS. Health Psychology 2004;23(4):413-418.

• The authors, faculty at the Department of Psychology at the University of Miami, examined the relationship between social support, depression, positive states of mind, and adherence to antiretroviral medications among HIV positive men and women. The authors’ goals were to show that social support would improve adherence by decreasing depressive symptoms and improving positive states of mind. Social support was measured using a Social Provisions Scale that evaluates the patients’ relationships with other people. Depression was measured using a Beck Depression Inventory questionnaire and positive state of mind was monitored with a PSOM Scale. Adherence was monitored with The Adherence to Combination Therapy Guide as well as by viral load and CD4 counts. The authors found that increased social support and improved positive states of mind were directly related to improved adherence while higher depression scores were related to nonadherence. While this study does demonstrate the impact psychological factors can have on a patient’s adherence to HAART, it was limited by a small population sample (n=90).

Stone VE, Jordan J, Tolson J, et al. Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy: self-report of the relative importance of multiple attributes of highly active antiretroviral therapy (HAART) regimens in predicting adherence. JAIDS 2004;36(3):808-816.

• The authors, faculty at the Department of Medicine at Harvard Medical School, evaluated patient perceptions on adherence to antiretroviral therapy based on ten attributes of HAART. These attributes included total pills per day, pill size, side effects, dietary restriction, dosing frequency, number of prescriptions, number of refills, number of copayments, number of pill bottles, and if the dosing regimen required bedtime dosing. The study was conducted using a questionnaire sent out to 299 HIV positive patients currently receiving HAART. The questionnaire evaluated the patients’ perceptions on the impact of their adherence based on the ten different attributes of a regimen. These results were then scored on a Likert scale based on the likelihood of the patients adhering to seven different actual regimens. The three attributes that were determined to have the greatest impact on adherence were pill count, dosing frequency, and adverse effects. The regimen that had the highest predicted adherence was a twice-daily regimen with two pills per day, no dietary restrictions, and only one required prescription and copayment. The regimen that had the lowest predicted adherence was a twice-daily regimen with 13 pills per day, food requirements, and three prescriptions and copayments. The authors concluded that practitioners should take into account the importance of different attributes of a regimen when selecting HAART therapy for a patient.

Smith ST, Golin CE, Reif S. Influence of time stress and other variables on counseling by pharmacists about antiretroviral medications. American Journal of Health-System Pharmacy 2004;61(11):1120-1129.

• The authors, pharmacists and professors at the School of Pharmacy at the University of North Carolina, evaluated the medication counseling practices of pharmacists working in an ambulatory setting that care for beneficiaries of the North Carolina AIDS Drug Assistance Program. Questionnaires were mailed to the pharmacy managers of 573 pharmacies inquiring about the frequency of adherence counseling for HIV patients and the time allocated, spent, and needed to dispense a new prescription and a refill for an antiretroviral to these patients. The pharmacists’ time pressure and time stress were then calculated; time pressure being a percentage of the time needed over the time allocated and time stress was defined as either needing or not needing more allocated time to provide optimal care to these patients. The questionnaires revealed that 59% of pharmacists did not have enough time to provide adherence counseling and 45% of pharmacists admitted their patients did not receive this counseling at all. The authors concluded that time pressure limited the pharmacists’ ability to provide adequate counseling to these patients leading to suboptimal care of the HIV positive patient population.

Wood E, Hogg RS, Yip B, et al. The impact of adherence on CD4 cell count responses among HIV infected patients. JAIDS 2004;35(3):261-268.

• The authors, members of the British Columbia Center for Excellence in HIV/AIDS, examine the effect on CD4 count in antiretroviral-naïve patients when initiating a new HAART therapy and evaluate the impact of adherence. The patients were divided into three groups by their CD4 count (<50, 50-199, and >=200 cells/microL). The patients (n=1522) were started on a triple drug combination which included two NRTIs and either a PI or a NNRTI. CD4 count was measured at initiation of the study and then again at 5 15-week intervals. Adherence was measured by how long the dispensed quantity of medication would last. At the end of the fifth 15-week follow-up, the authors found that the patients starting with a CD4 count of <50 had increased to 200 cells/microL for adherent patients versus 60 cells/microL for nonadherent patients. Patients with CD4 counts between 50-199 cells/microL at baseline increased to 300 cells/microL versus 125 cells/microL, respectively. This study demonstrated a significant correlation between substantial CD4 gains and adherence.

Kalichman SC, Cain D, Cherry C et al. Pillboxes and antiretroviral adherence: prevalence of use, perceived benefits, and implications for electronic medication monitoring devices. AIDS Patient Care and STDs 2005;19(12):833-839.

• The authors, faculty at the Department of Psychology at the University of Connecticut, conducted a study to examine the characteristics of HIV positive patients who use pillboxes and evaluated the impact of pillbox use on research using electronic monitoring devises (EMD) for adherence measurement. This study used anonymous surveys sent to HIV positive patients who were currently receiving HAART. Of the 160 participants who were surveyed, 39% were currently using a pillbox. The study showed that pillbox users were significantly less likely to have missed any doses of medication within one day of assessment, evaluated by self-report, and more likely to have an undetectable viral load. Upon questioning whether the participants would be willing to discontinue using their pillbox to join a trial using an EMD, 76% of the patients agreed they would. This statistic was evaluated because many trials using EMD, such as a MEMS cap, exclude patients who use pillboxes which places limitations on the study. This study demonstrated a positive effect on adherence when patients use reminders such as pillboxes. This study also suggested that improvements could be made in many research trials by having pillbox-like electronic monitoring device available rather than eliminating patients who use pillboxes.

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