C. Keith Beck

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.

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.

Constitutional symptoms and health-related quality of life in patients with symptomatic HIV disease

PURPOSE To assess the severity of constitutional symptoms in persons with human immunodeficiency virus (HIV) infection, and their relationship to health-related quality of life (HRQOL). PATIENTS AND METHODS Two hundred five HIV-infected patients (93% male, 26% African American, 28% Latino, 39% white, 7% other ethnicity) with diarrhea, fever, or weight loss were studied at a county hospital and a Veterans Administration hospital in southern California. Consenting subjects were administered a battery that included 11 scales measuring various aspects of health-related quality of life and detailed questions about six constitutional symptoms or symptom complexes (myalgias, exhaustion, anorexia/nausea/vomiting, night sweats, fever, and weight loss) as well as about other manifestations of HIV disease. RESULTS Constitutional symptoms except weight loss were all strongly related to all measures of quality of life. On 0 (worst) to 100 (best) point scales, mean scores ranged from 34 (for individuals having all five symptoms other than weight loss) to 78 (for those with none) for physical function, 43 to 79 for emotional well-being, and 36 to 73 for social function. Adjustment for helper T-lymphocyte counts, duration of illness, and demographic characteristics did not diminish these associations. CONCLUSION The presence, number, and severity of constitutional symptoms in HIV disease is strongly related to health-related quality of life in symptomatic HIV-infected individuals. Identifying and treating these very common symptoms has the potential to improve quality of life in these patients.

The Prospective Effect of Access to Medical Care on Health-Related Quality-of-Life Outcomes in Patients with Symptomatic HIV Disease

OBJECTIVES This study examined the prospective effect of reported access to medical care on health-related quality-of-life outcomes in patients with symptomatic human immunodeficiency virus (HIV) disease. METHODS A cohort study was designed with interviews at baseline, follow-up interviews at 3 months after baseline, mortality follow-up through 6 months after baseline, and medical record reviews for selected baseline clinical data. Participants were HIV-infected patients who were receiving ambulatory and/or hospital care at one county-run municipal and one Veterans Administration hospital in metropolitan Los Angeles and were interviewed about access to medical care (using a reliable 9-item scale assessing affordability, availability, and convenience of medical care). Access to care reported by this sample was compared with that of 2,471 patients with other chronic diseases from the Medical Outcomes Study. The main outcome measures were composite scores for physical and mental health-related quality of life 3 months after baseline, derived from a validated 56-item instrument, scored from 0 to 100, and controlling for baseline health-related quality of life. RESULTS Overall reported access to medical care in this sample was significantly poorer than that for patients with other chronic diseases (means scores were 63 and 73, respectively). The sample was categorized into tertiles of initial physical and mental health-related quality of life and into groups with initial high versus low access to care. Among those in the middle tertile of physical health-related quality of life at baseline, those with high access improved in physical health scores by 10.2 points relative to those with low access. Those in the low and middle tertiles of initial mental health improved in mental health to a significantly greater extent for those with high versus low access. There were nonsignificant trends toward similar effects for most other subgroups. The effects of access on health-related quality-of-life outcomes were generally robust in multivariate regression analyses that included CD4, hemoglobin, albumin, insurance status, and sociodemographic characteristics. CONCLUSIONS Access to care at baseline predicted better physical and mental health outcomes at 3 months for those in the middle tertile of physical health and for those in the bottom and middle tertiles of mental health at baseline. Increasing access to care for poor public hospital patients with HIV infection may help to improve health-related quality-of-life outcomes among selected persons with advanced disease.

Concurrent Cerebral American Trypanosomiasis and Toxoplasmosis in a Patient with AIDS

We report a case of concurrent cerebral infection with Trypanosoma cruzi and Toxoplasma gondii in a patient with acquired immunodeficiency syndrome (AIDS). A 22-year-old El Salvadoran man initially improved during receipt of antitoxoplasmosis therapy, but he had rapidly progressive hemiplegia. Magnetic resonance imaging showed an abnormal finding in the left internal capsule, and cytological analysis of cerebrospinal fluid revealed T. cruzi trypomastigotes. Despite prompt therapy with nifurtimox, the patients mental status declined, and he died of nosocomial complications. Although infrequent, T. cruzi infection should be considered in the differential diagnosis of brain lesions in patients with AIDS from regions of endemicity.

Health Related Quality of Life in HIV Disease

The structure of health-related quality of life (HRQOL) in HIV disease is examined in 205 symptomatic HIV+ individuals receiving care at two West Coast public hospitals. A 64-item HRQOL battery, tapping aspects of HRQOL of particular relevance to individuals with HIV disease, was administered and found to yield reliable self-report data. Confirmatory factor analysis provides support for a two-factor model of HRQOL: (a) a physical health dimension defined by physical function, role function, freedom from pain, disability days, and quality of sex life, and (b) a mental health dimension defined by overall quality of life, emotional well-being, hopefulness, lack of loneliness, will to function, quality of family life, quality of friendships, and cognitive function/distress. Correlations of HRQOL measures with social support, access to care, coping, and symptom measures are reported and discussed.

Validation of a new measure of diarrhea

Adequate measures of diarrheal disease are important to assess severity for clinical use and outcomes research. We developed a questionnaire to assess diarrhea severity and complications, and administered it to 205 HIV positive patients with diarrhea, fever, or weight loss. Noteworthy variations in stool form were reported by individuals and across subjects. Self-reported diarrhea correlated with the occurrence of any stool picture without form. However, verbal descriptors “loose” and “semiformed” had little value in assessment of diarrheal disease. Both verbal and pictorial stool descriptors correlated well with diarrhea complications (pain, urgency, tenesmus, incontinence, and nocturnal diarrhea). By factor analysis, discomfort and nondiscomfort diarrhea complications loaded on different factors, consistent with clinical experience that discomfort is a distinct problem in diarrheal disease. In summary we have developed an instrument to precisely characterize diarrhea severity that correlates well with clinically important events such as incontinence and abdominal pain.

Impact of Antiretroviral Regimen Switches on Adherence

Abstract Purpose: An understanding of the situations in which adherence lapses occur is critical to the design of effective interventions to enhance adherence. We investigated whether a switch in antiretroviral medications affected adherence by examining a prospective observational cohort of 128 patients who began a new antiretroviral regimen. Method: Adherence was measured using electronic devices, pill counts, and self-reports, which were combined into a composite adherence measure and expressed as the proportion of prescribed medication taken. Results: During 1,056 person-months of follow-up, 129 medication regimen changes occurred among 84 patients (66% of participants). Among the 89 analyzable switches (representing 66 patients), the most common reasons for switch included pill to liquid ritonavir (n = 26), gastrointestinal intolerance (n = 11), virologic failure (n = 8), and peripheral neuropathy (n = 7). Overall, mean adherence prior to regimen switch exceeded mean adherence after regimen switch (0.75 vs. 0.70; p = .035). Among subgroups of switches, adherence decreased significantly after switching from pill to liquid ritonavir (0.83 vs. 0.68; p < .001). When this group was excluded, there was no change in adherence after switches (0.72 vs. 0.71; p = .74). Conclusion: Antiretroviral regimen changes are not associated with adherence improvement and may be associated with declining adherence when a new regimen is unpalatable. Antiretroviral regimen changes should trigger reassessment of adherence and, when appropriate, adherence intervention.PURPOSE An understanding of the situations in which adherence lapses occur is critical to the design of effective interventions to enhance adherence. We investigated whether a switch in antiretroviral medications affected adherence by examining a prospective observational cohort of 128 patients who began a new antiretroviral regimen. METHOD Adherence was measured using electronic devices, pill counts, and self-reports, which were combined into a composite adherence measure and expressed as the proportion of prescribed medication taken. RESULTS During 1,056 person-months of follow-up, 129 medication regimen changes occurred among 84 patients (66% of participants). Among the 89 analyzable switches (representing 66 patients), the most common reasons for switch included pill to liquid ritonavir (n = 26), gastrointestinal intolerance (n = 11), virologic failure (n = 8), and peripheral neuropathy (n = 7). Overall, mean adherence prior to regimen switch exceeded mean adherence after regimen switch (0.75 vs. 0.70; p =.035). Among subgroups of switches, adherence decreased significantly after switching from pill to liquid ritonavir (0.83 vs. 0.68; p <.001). When this group was excluded, there was no change in adherence after switches (0.72 vs. 0.71; p =.74). CONCLUSION Antiretroviral regimen changes are not associated with adherence improvement and may be associated with declining adherence when a new regimen is unpalatable. Antiretroviral regimen changes should trigger reassessment of adherence and, when appropriate, adherence intervention.