Carol E. Golin

A Prospective Study of Predictors of Adherence to Combination Antiretroviral Medication

AbstractOBJECTIVE: Adherence to complex antiretroviral therapy (ART) is critical for HIV treatment but difficult to achieve. The development of interventions to improve adherence requires detailed information regarding barriers to adherence. However, short follow-up and inadequate adherence measures have hampered such determinations. We sought to assess predictors of long-term (up to 1 year) adherence to newly initiated combination ART using an accurate, objective adherence measure. DESIGN: A prospective cohort study of 140 HIV-infected patients at a county hospital HIV clinic during the year following initiation of a new highly active ART regimen. MEASURES AND MAIN RESULTS: We measured adherence every 4 weeks, computing a composite score from electronic medication bottle caps, pill count and self-report. We evaluated patient demographic, biomedical, and psychosocial characteristics, features of the regimen, and relationship with one’s HIV provider as predictors of adherence over 48 weeks. On average, subjects took 71% of prescribed doses with over 95% of patients achieving suboptimal (<95%) adherence. In multivariate analyses, African-American ethnicity, lower income and education, alcohol use, higher dose frequency, and fewer adherence aids (e.g., pillboxes, timers) were independently associated with worse adherence. After adjusting for demographic and clinical factors, those actively using drugs took 59% of doses versus 72% for nonusers, and those drinking alcohol took 66% of doses versus 74% for nondrinkers. Patients with more antiretroviral doses per day adhered less well. Participants using no adherence aids took 68% of doses versus 76% for those in the upper quartile of number of adherence aids used. CONCLUSIONS: Nearly all patients’ adherence levels were suboptimal, demonstrating the critical need for programs to assist patients with medication taking. Interventions that assess and treat substance abuse and incorporate adherence aids may be particularly helpful and warrant further study.

Interventions to Improve Adherence to Self-administered Medications for Chronic Diseases in the United States: A Systematic Review

BACKGROUND Suboptimum medication adherence is common in the United States and leads to serious negative health consequences but may respond to intervention. PURPOSE To assess the comparative effectiveness of patient, provider, systems, and policy interventions that aim to improve medication adherence for chronic health conditions in the United States. DATA SOURCES Eligible peer-reviewed publications from MEDLINE and the Cochrane Library indexed through 4 June 2012 and additional studies from reference lists and technical experts. STUDY SELECTION Randomized, controlled trials of patient, provider, or systems interventions to improve adherence to long-term medications and nonrandomized studies of policy interventions to improve medication adherence. DATA EXTRACTION Two investigators independently selected, extracted data from, and rated the risk of bias of relevant studies. DATA SYNTHESIS The evidence was synthesized separately for each clinical condition; within each condition, the type of intervention was synthesized. Two reviewers graded the strength of evidence by using established criteria. From 4124 eligible abstracts, 62 trials of patient-, provider-, or systems-level interventions evaluated 18 types of interventions; another 4 observational studies and 1 trial of policy interventions evaluated the effect of reduced medication copayments or improved prescription drug coverage. Clinical conditions amenable to multiple approaches to improving adherence include hypertension, heart failure, depression, and asthma. Interventions that improve adherence across multiple clinical conditions include policy interventions to reduce copayments or improve prescription drug coverage, systems interventions to offer case management, and patient-level educational interventions with behavioral support. LIMITATIONS Studies were limited to adults with chronic conditions (excluding HIV, AIDS, severe mental illness, and substance abuse) in the United States. Clinical and methodological heterogeneity hindered quantitative data pooling. CONCLUSION Reduced out-of-pocket expenses, case management, and patient education with behavioral support all improved medication adherence for more than 1 condition. Evidence is limited on whether these approaches are broadly applicable or affect longterm medication adherence and health outcomes. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Prevalence and predictors of Highly active antiretroviral therapy use in patients with HIV infection in the United States

Background: Highly active antiretroviral therapy (HAART) became standard for HIV in 1996. Studies at that time showed that most people infected with HIV had initiated HAART, but that members of minority groups and poor people had lower HAART use. It is not known whether high levels of HAART use have been sustained or whether socioeconomic and racial disparities have diminished over time. Objectives: To determine the proportion of patients who had received and were receiving HAART by January 1998, and to evaluate predictors of HAART receipt. Design and Participants: Prospective cohort study of a national probability sample of 2267 adults receiving HIV care who completed baseline, first follow‐up, and second follow‐up interviews from January 1996 to January 1998. Main outcome variables: Proportion currently using HAART at second follow‐up (August 1997 to January 1998), contrasted with the cumulative proportions using HAART at any time before January 1998 and before December 1996. Analyses: Bivariate and multiple logistic regression analysis of population characteristics predicting current use of HAART at the time of the second follow‐up interview. Results: The proportion of patients ever having received HAART increased from 37% in December 1996 to 71% by January 1998, but only 53% of people were receiving HAART at the time of the second follow‐up interview. Differences between sociodemographic groups in ever using HAART narrowed after 1996. In bivariate analysis, several groups remained significantly less likely to be using HAART at the time of the second follow‐up interview: blacks, male and female drug users, female heterosexuals, people with less education, those uninsured and insured by Medicaid, those in the Northeast, and those with CD4 counts of ≥500 cells/&mgr;l (all p < .05). Using multiple logistic regression analysis, low CD4 count (for CD4 <50 cells/&mgr;l: odds ratio [OR], 3.20; p < .001) remained a significant predictor of current HAART use at the time of the second follow‐up interview, but lack of insurance (OR, 0.71; p < .05) predicted not receiving HAART. Conclusions: The proportion of persons under HIV care in the United States who had ever received HAART increased to over 70% of the affected population by January 1998 and the disparities in use between groups narrowed but did not disappear. However, nearly half of those eligible for HAART according to the U.S. Department of Health and Human Services guidelines were not actually receiving it nearly 2 years after these medications were first introduced. Strategies to promote the initiation and continuation of HAART are needed for those without contraindications and those who can tolerate it.

How Well Do Clinicians Estimate Patients' Adherence to Combination Antiretroviral Therapy?

AbstractOBJECTIVE: Adherence to combination antiretroviral therapy is critical for clinical and virologic success in HIV-infected patients. To combat poor adherence, clinicians must identify nonadherent patients so they can implement interventions. However, little is known about the accuracy of these assessments. We sought to describe the accuracy of clinicians’ estimates of patients’ adherence to combination antiretroviral therapy. SETTING: Public HIV clinic. DESIGN: Prospective cohort study. During visits, we asked clinicians (nurse practitioners, residents and fellow, and their supervising attending physicians) to estimate the percentage of antiretroviral medication taken by patients over the last 4 weeks and predicted adherence over the next 4 weeks. Adherence was measured using electronic monitoring devices, pill counts, and self-reports, which were combined into a composite adherence measure. PATIENTS AND PARTICIPANTS: Clinicians estimated 464 episodes of adherence in 82 patients. RESULTS: Among the 464 adherence estimates, 264 (57%) were made by principal care providers (31% by nurse practitioners, 15% by fellows, 6% by residents, and 5% by staff physicians) and 200 (43%) by supervising attending physicians. Clinicians’ overestimated measured adherence by 8.9% on average (86.2% vs 77.3%). Greater clinician inaccuracy in adherence prediction was independently associated with higher CD4 count nadir (1.8% greater inaccuracy for every 100 CD4 cells, P=.005), younger patient age (3.7% greater inaccuracy for each decade of age, P=.02), and visit number (P=.02). Sensitivity of detecting nonadherent patients was poor (24% to 62%, depending on nonadherence cutoff). The positive predictive value of identifying a patient as nonadherent was 76% to 83%. CONCLUSIONS: Clinicians tend to overestimate medication adherence, inadequately detect poor adherence, and may therefore miss important opportunities to intervene to improve antiretroviral adherence.

Barriers to accessing HIV/AIDS care in North Carolina: rural and urban differences.

Abstract Many HIV-positive individuals face multiple barriers to care and therefore frequently experience unmet medical and support services needs. Rural areas often lack the infrastructure to support the delivery of comprehensive HIV services; however, few studies have examined service barriers faced by rural residents with HIV/AIDS, particularly in the South where two-thirds of people living with HIV/AIDS in rural areas reside. We surveyed North Carolina HIV/AIDS case managers (N=111) employed at state-certified agencies regarding barriers to medical and support services that influence medication adherence for their rural and urban-living clients. For each of the seven barriers assessed (long travel for care, HIV-related stigma, and a lack of transportation; HIV-trained medical practitioners; housing; mental health services and substance abuse treatment), a substantial proportion of case managers (29–67%) reported it was a ‘major problem’. For five of the seven barriers, rural case managers were significantly more likely to identify the barrier as a ‘major problem’. Multivariate analysis revealed that rural case managers and case managers with more female clients reported a greater number of barriers. Because unmet medical and support service needs may result in poorer outcomes for HIV-positive individuals, barriers to these services must be identified and addressed, particularly in rural areas which may be highly underserved.

Repeated Measures Longitudinal Analyses of HIV Virologic Response as a Function of Percent Adherence, Dose Timing, Genotypic Sensitivity, and Other Factors

Background: Adherence to antiretroviral medications is critical to achieving HIV viral suppression. Studies have been limited to cross-sectional analyses using measures that reflect only the percentage of prescribed doses taken (percent adherence), however. The contribution of dose timing and other factors to achieving virologic suppression has received less scrutiny. Methods: In a longitudinal study, we collected detailed adherence information using multiple tools along with demographic, clinical, social-behavioral, and virologic measures. Subjects were followed for 48 weeks. Percent adherence, dose-timing, genotypic sensitivity, and virologic outcomes were collected every 4 weeks. Repeated measures mixed effects models (RMMEMs) were used to model the relation between virologic outcomes and adherence as well as genotypic sensitivity and others. Results: Of the 141 subjects, mean percent adherence was 73% with a downward trend. Viral load (VL) dropped significantly (P = 0.01) over time. RMMEMs revealed that higher genotypic sensitivity, higher percent adherence, lower baseline VL, longer inclusion in the study, earlier HIV stage, and smaller dose-timing error were significantly associated with lower VL. In multivariate modeling, a 0.50 increase in the genotypic sensitivity score, a 10% increase in adherence, and a decrease of 3 hours of dose-timing error were associated with a decrease in log10 HIV RNA at 48 weeks of 0.69, 0.54, and 0.48, respectively (P < 0.05 for each). Conclusions: Long-term viral suppression requires consistent and high percent adherence accompanied by optimal interdose intervals. Efforts to improve viral outcomes should address not only missed doses but excessive variation in dose timing and prevention of adherence decline over time. Preventing the development and transmission of resistant variants is also critically important.

Medication Therapy Management Interventions in Outpatient Settings A Systematic Review and Meta-analysis

IMPORTANCE Medication therapy management (MTM) services (also called clinical pharmacy services) aim to reduce medication-related problems and their downstream outcomes. OBJECTIVE To assess the effect of MTM interventions among outpatients with chronic illnesses. DATA SOURCES MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts through January 9, 2014. STUDY SELECTION Two reviewers selected studies with comparators and eligible outcomes of ambulatory adults. DATA EXTRACTION AND SYNTHESIS Dual review of titles, abstracts, full-text, extractions, risk of bias, and strength of evidence grading. We conducted meta-analyses using random-effects models. MAIN OUTCOMES AND MEASURES Medication-related problems, morbidity, mortality, quality of life, health care use, costs, and harms. RESULTS Forty-four studies met the inclusion criteria. The evidence was insufficient to determine the effect of MTM interventions on most evaluated outcomes (eg, drug therapy problems, adverse drug events, disease-specific morbidity, disease-specific or all-cause mortality, and harms). The interventions improved a few measures of medication-related problems and health care use and costs (low strength of evidence) when compared with usual care. Specifically, MTM interventions improved medication appropriateness (4.9 vs 0.9 points on the medication appropriateness index, P < .001), adherence (approximately 4.6%), and percentage of patients achieving a threshold adherence level (odds ratios [ORs] ranged from 0.99 to 5.98) and reduced medication dosing (mean difference, -2.2 doses; 95% CI, -3.738 to -0.662). Medication therapy management interventions reduced health plan expenditures on medication costs, although the studies reported wide CIs. For patients with diabetes mellitus or heart failure, MTM interventions lowered the odds of hospitalization (diabetes: OR, 0.91 to 0.93 based on type of insurance; adjusted hazard rate for heart failure: 0.55; 95% CI, 0.39 to 0.77) and hospitalization costs (mean differences ranged from -

Impoverished diabetic patients whose doctors facilitate their participation in medical decision making are more satisfied with their care.

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The Harms of Screening: A Proposed Taxonomy and Application to Lung Cancer Screening

398.98). The interventions conferred no benefit for patient satisfaction and most measures of health-related quality of life (low strength). CONCLUSIONS AND RELEVANCE We graded the evidence as insufficient for most outcomes because of inconsistency and imprecision that stem in part from underlying heterogeneity in populations and interventions. Medication therapy management interventions may reduce the frequency of some medication-related problems, including nonadherence, and lower some health care use and costs, but the evidence is insufficient with respect to improvement in health outcomes.

Discrimination, distrust, and racial/ethnic disparities in antiretroviral therapy adherence among a national sample of HIV-infected patients.

OBJECTIVE: Greater participation in medical decision making is generally advocated for patients, and often advocated for those with diabetes. Although some studies suggest that diabetic patients prefer to participate less in decision making than do healthy patients, the empirical relationship between such participation and diabetic patients’ satisfaction with their care is currently unknown. We sought to characterize the relationship between aspects of diabetic patients’ participation in medical decision making and their satisfaction with care.DESIGN: Cross-sectional observational study.SETTING: A general medical county hospital-affiliated clinic.PARTICIPANTS: One hundred ninety-eight patients with type 2 diabetes.MAIN MEASURES: Interviews conducted prior to the doctor visit assessed patients’ desire to participate in medical decision making, baseline satisfaction (using a standardized measure), and sociodemographic and clinical characteristics. Postvisit interviews of those patients assessed their visit satisfaction and perception of their doctor’s facilitation of patient involvement in care. A discrepancy score was computed for each subject to reflect the difference between the previsit stated desire regarding participation and the postvisit report of their experience of participation.RESULTS: Overall, patients reported low postvisit satisfaction relative to national standards (mean of 70 on a 98-point scale). Patients perceived a high level of facilitation of participation (mean 88 on a 100-point scale). Facilitation of participation and the discrepancy score both independently predicted greater visit satisfaction. In particular, a 13-point (1 SD) increase in the perceived facilitation score resulted in a 12-point (0.87 SD) increase in patient satisfaction, and a 1.22 point increase (1 SD) in the discrepancy score (the extent to which the patient was allowed more participation than, at previsit, he or she desired) resulted in a 6-point (0.5 SD) increase in the satisfaction score, even after controlling for initial desire to participate. For women, but not for men, physician facilitation of participation was a positive predictor of satisfaction; for men, but not women, desire to participate was a significant positive predictor of visit satisfaction.CONCLUSION: Clinicians may feel reassured that encouraging even initially reluctant patients with diabetes to participate in medical decision making may be associated with increased patient satisfaction. Greater patient participation has the potential to improve diabetic self-care because of the likely positive effect of patient satisfaction on adherence to treatment. Further research to assess the prospective effects of enhancing physician facilitation of patient participation is likely to yield important information for the effective treatment of chronically ill patients.