Julia H. Arnsten

Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: Comparison of self-report and electronic monitoring

To compare electronically monitored (MEMS) with self-reported adherence in drug users, including the impact of adherence on HIV load, we conducted a 6-month observational study of 67 antiretroviral-experienced current and former drug users. Adherence (percentage of doses taken as prescribed) was calculated for both the day and the week preceding each of 6 research visits. Mean self-reported 1-day adherence was 79% (median, 86%), and mean self-reported 1-week adherence was 78% (median, 85%). Mean MEMS 1-day adherence was 57% (median, 52%), and mean MEMS 1-week adherence was 53% (median, 49%). One-day and 1-week estimates were highly correlated (r>.8 for both measures). Both self-reported and MEMS adherence were correlated with concurrent HIV load (r=.43-.60), but the likelihood of achieving virologic suppression was greater if MEMS adherence was high than if self-reported adherence was high. We conclude that self-reported adherence is higher than MEMS adherence, but a strong relationship exists between both measures and virus load. However, electronic monitoring is more sensitive than self-report for the detection of nonadherence and should be used in adherence intervention studies.

A prospective study of adherence and viral load in a large multi-center cohort of HIV-infected women

Objectives: To examine the relationship between antiretroviral adherence and viral load, and to determine the predictors of adherence over time in HIV-infected women. Design: Prospective observational study. Methods: One-hundred sixty-one HIV-infected women who were taking antiretroviral therapy for a median of 3.0 years were recruited from the HIV Epidemiology Research Study, a multicenter cohort study of HIV infection in women. Antiretroviral adherence (percent of doses taken as prescribed) was measured over a 6-month period using MEMS caps. At baseline and follow-up, CD4 lymphocyte count and viral load were measured, and a standardized interview was administered to elicit medication history and drug use behaviors. To examine changes in adherence over time, the mean adherence to all antiretroviral agents was calculated for each monitored month. Results: Adherence varied significantly over time (P < 0.001), ranging from a mean of 64% in month 1 to 45% in month 6. Nearly one-fourth of the participants had a 10% or greater decrease in adherence between consecutive months. Virologic failure occurred in 17% of women with adherence of ⩾ 88%, 28% of those with 45–87% adherence, 43% of those with 13–44% adherence, and 71% of those with ⩽ 12% adherence. In multivariate analysis, factors predicting lower adherence included active drug use, alcohol use, more frequent antiretroviral dosing, shorter duration of antiretroviral use, younger age, and lower initial CD4 lymphocyte count. Conclusions: Antiretroviral adherence is not stable over time. Interventions aimed at monitoring and improving long-term adherence in women are urgently needed.

Practical and Conceptual Challenges in Measuring Antiretroviral Adherence

Summary:Accurate measurement of antiretroviral adherence is essential for targeting and rigorously evaluating interventions to improve adherence and prevent viral resistance. Across diseases, medication adherence is an individual, complex, and dynamic human behavior that presents unique measurement challenges. Measurement of medication adherence is further complicated by the diversity of available measures, which have different utility in clinical and research settings. Limited understanding of how to optimize existing adherence measures has hindered progress in adherence research in HIV and other diseases. Although self-report is the most widely used adherence measure and the most promising for use in clinical care and resource-limited settings, adherence researchers have yet to develop evidence-based standards for self-reported adherence. In addition, the use of objective measures, such as electronic drug monitoring or pill counts, is limited by poor understanding of the source and magnitude of error biasing these measures. To address these limitations, research is needed to evaluate methods of combining information from different measures. The goals of this review are to describe the state of the science of adherence measurement, to discuss the advantages and disadvantages of common adherence measurement methods, and to recommend directions for improving antiretroviral adherence measurement in research and clinical care.

Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection.

Background:Osteopenia has been described in HIV-infected persons, but most studies have not focused on aging men, have not included an HIV-negative comparison group with similar risks to those of the HIV-infected men, or lacked data on fracture rates. Methods:We analyzed bone mineral density (BMD) and incident fractures in 559 men who were ≥ 49 years old with or at-risk for HIV, including 328 with and 231 without HIV infection. Results:Median age was 55 years, 56% were black and 89% had used illicit drugs. In unadjusted analysis, BMD was lower in HIV-infected compared with HIV-uninfected men at the femoral neck (0.97 ± 0.14 versus 1.00 ± 0.15 g/cm2; P < 0.05) and lumbar spine (1.17 ± 0.20 versus 1.20 ± 0.21 g/cm2; P = 0.06); both differences were significant (P < 0.05) after adjusting for age, weight, race, testosterone level, and prednisone and illicit drug use. Non-black race and body weight were independently associated with BMD at both measurement sites and methadone therapy was independently associated with spine BMD. Among HIV-infected men, 87% had taken antiretrovirals and 74% had taken protease inhibitors, but their use was not associated with BMD. Among men who had at least one subsequent study visit (94%), incident fracture rates per 100 person-years differed among men with normal BMD, osteopenia and osteoporosis (1.4 versus 3.6 versus 6.5; P < 0.01). A 38% increase in fracture rate among HIV-infected men was not statistically significant. Conclusions:HIV infection is independently associated with modestly reduced BMD in aging men, and decreased BMD is associated with increased fracture risk.

Association Between Alcohol Consumption and Both Osteoporotic Fracture and Bone Density

OBJECTIVE Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling. METHODS MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force. RESULTS We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk=0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk=1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers. CONCLUSION Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined.

Determinants of compliance with anticoagulation: A case-control study

BACKGROUND The number of patients for whom long-term anticoagulation is indicated has increased dramatically over the past decade. Good patient compliance is necessary to safely realize the benefits of anticoagulation, yet barriers to compliance with anticoagulation therapy have not been studied. METHODS We conducted a case-control study in the Anticoagulation Therapy Unit (ATU) at Massachusetts General Hospital. Forty-three patients who had been discharged from the ATU for noncompliance (cases) and 89 randomly selected compliant ATU controls were interviewed. Noncompliant cases had self-discontinued warfarin or were taking warfarin with inadequate monitoring of international normalized ratio (INR) levels. Telephone interviews assessed sociodemographic features, indication for anticoagulation, patient satisfaction, and health beliefs. RESULTS Noncompliant cases were more likely to be younger (mean 53.7 years versus 68.7 years, P < 0.0001), male (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.5, 8.2) and nonwhite (OR 6.4, 95% CI 1.9, 21.9), and less likely to have had a stroke or transient ischemic attack (OR 0.2, 95% CI 0.1, 0.7). In open-ended questioning, cases were more likely to report that they did not know why warfarin had been prescribed (OR 4.4, 95% CI 1.4, 14.2). Noncompliant cases were more likely not to have a regular physician (OR 11.1, 95% CI 3.6, 50.0); among patients with a regular physician, noncompliant cases were more likely to feel dissatisfied. Examination of health beliefs revealed that noncompliant cases felt more burdened by taking warfarin, and perceived fewer health benefits. CONCLUSIONS Patients who are noncompliant with warfarin share distinctive clinical characteristics. Notably, younger, male patients who have not experienced a thromboembolic event are more likely to forego INR testing or to stop anticoagulation therapy completely. Improved patient education, physician involvement, and ease of monitoring may improve compliance, particularly among younger male patients.

Gender differences in factors associated with adherence to antiretroviral therapy

OBJECTIVE: To identify gender differences in social and behavioral factors associated with antiretroviral adherence.DESIGN: Prospective cohort study.SETTING: Methadone maintenance program.PARTICIPANTS: One hundred thirteen HIV-seropositive current or former opioid users.MEASUREMENTS AND MAIN RESULTS: Participants were surveyed at baseline about social and behavioral characteristics and at monthly research visits about drug and alcohol use and medication side effects. Electronic monitors (MEMS) were used to measure antiretroviral adherence. Median adherence among women was 27% lower than among men (46% vs. 73%; P<.05). In gender-stratified multivariate models, factors associated with worse adherence in men included not belonging to an HIV support group (P<.0001), crack/cocaine use (P<.005), and medication side effects (P=.01). Among women, alcohol use (P=.005), heroin use (P<.05), and significant medication side effects (P<.005) were independently associated with worse adherence. In a model including both men and women, worse adherence was associated with lack of long-term housing (P<.005), not belonging to any HIV support groups (P<.0005), crack or cocaine use (P<.01), and medication side effects (P<.0005). In addition, worse adherence was associated with the interaction between female gender and alcohol use (P ≤ .05).CONCLUSIONS: In this cohort of current and former opioid users, gender-stratified analysis demonstrated that different social and behavioral factors are associated with adherence in men and women. Among both men and women, worse adherence was associated with lack of long-term housing, not belonging to an HIV support group, crack/cocaine use, and medication side effects. Among women only, alcohol use was associated with worse adherence.

Impact of Adherence, Knowledge, and Quality of Life on Anticoagulation Control

BACKGROUND: Patients receiving chronic warfarin therapy who have poor anticoagulation control are at increased risk for adverse events. However, it is unknown how adherence to warfarin, patient demographics, patient knowledge about therapy, and perceived impact of warfarin therapy on quality of life are associated with anticoagulation control. OBJECTIVE: To determine the association between these patient factors and anticoagulation control in patients attending 2 anticoagulation clinics in the Bronx, New York City. METHODS: A cross-sectional survey of 52 patients was conducted. The 4-item Morisky survey was used to assess self-reported adherence. Patient knowledge about warfarin therapy and the perceived impact of warfarin therapy on quality of life were determined by self-administered questionnaires. Associations between adherence, patient knowledge, impact of warfarin therapy on quality of life, and anticoagulation control were determined with t-tests, χ2 analysis, and logistic regression. RESULTS: Only 14% of patients had good anticoagulation control. Adequate adherence was reported by 50% of patients and was significantly associated with good anticoagulation control (p = 0.01). Thirty-seven percent of participants had good knowledge of anticoagulation, and 19% of participants reported that warfarin negatively impacted their quality of life. Knowledge about warfarin therapy and impact of warfarin on quality of life were not significantly associated with anticoagulation control. CONCLUSIONS: Adherence is one of many factors that contribute to anticoagulation control. Adequate adherence, as determined by the Morisky survey, was significantly associated with anticoagulation control. Patient demographic characteristics, knowledge about warfarin therapy, and perceived impact of warfarin on quality of life were not associated with anticoagulation control.

HIV infection and bone mineral density in middle-aged women

BACKGROUND Osteopenia is prevalent in persons with human immunodeficiency virus (HIV) infection and is part of a normal sequence of aging in women. Most studies of bone mineral density (BMD) and HIV infection have focused on men or have lacked a comparison group of individuals without HIV infection with similar behavioral risk factors. METHODS We analyzed BMD in 495 middle-aged women (defined as women > or =40 years of age); 263 women had HIV infection, and 232 women were HIV-negative with behavioral risk factors similar to those of the HIV-positive group. RESULTS The median age of the women in the study was 44 years, 54% were black, and 92% had used illicit drugs. Femoral neck BMD and lumbar spine BMD were reduced in women with HIV infection, compared with women without HIV infection (femoral neck BMD, 1.01+/-0.13 g/cm2 vs. 1.05+/-0.13 g/cm2; P=.001; lumbar spine BMD, 1.21+/-0.17 g/cm2 vs. 1.24+/-0.17 g/cm2; P=.04). In addition to HIV infection, other factors independently associated with lower BMD in both sites were being older, not being black, and having a low body weight. In race-stratified multivariate analyses, HIV infection was associated with BMD only in non-black women. Among HIV-positive women, 84% had taken antiretrovirals, and 62% had taken protease inhibitors, but their use was not associated with BMD. Methadone treatment was also independently associated with reduced lumbar spine BMD. CONCLUSION Middle-aged women with HIV infection have reduced BMD, compared with women at similar risk for HIV infection, independent of antiretroviral use. Among HIV-positive women, those who are not black, who are underweight, and who use opiates may be at particular risk. Although the prevalence of reduced BMD in this cohort was higher among women with HIV infection than among those without (27% vs. 19%), the overall prevalence of reduced BMD was low, compared with national estimates and with previous studies involving HIV-positive women and men.

HIV infection, drug use, and onset of natural menopause.

OBJECTIVE To study the relationship of HIV infection and drug use with the onset of natural menopause. METHODS Our analyses used the World Health Organizations definition of menopause (i.e., the date of the last menstrual period is confirmed after 12 months of amenorrhea) and baseline data from a prospective study. Semiannual interviews were conducted. Levels of HIV antibody and CD4+ cell counts were obtained. Menopause was identified at baseline or during 12 months of follow-up. Women ingesting reproductive hormones were excluded. Logistic regression analyses were used to assess factors associated with menopause. RESULTS Of 571 women, 53% were HIV infected, and 52% had used heroin or cocaine in the previous 5 years. The median age was 43 years (interquartile range [IQR], 40-46 years); 48.9% of the women were black, 40.4% were Hispanic, and 10.7% were white. The median body mass index was 29.1 kg/m2, and 90.4% of participants were current or former cigarette smokers. Menopause was identified in 102 women: 62 HIV-infected women (median age, 46 years; interquartile range [IQR], 39-49 years) and 40 uninfected women (median age, 47 years; IQR, 44.5-48 years). Factors independently associated with menopause included HIV infection (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.075-2.795), drug use (adjusted OR, 2.633; 95% CI, 1.610-4.308), and physical activity (adjusted OR, 0.895; 95% CI, 0.844-0.950). Among HIV-infected women, factors independently associated with menopause included CD4+ cell counts of >500 cells/mm3 (adjusted OR, 0.191; 95% CI, 0.076-0.4848) and 200-500 cells/mm3 (adjusted OR, 0.356; 95% CI, 0.147-0.813). CONCLUSION Our study shows that HIV infection and immunosuppression are associated with an earlier age at the onset of menopause. Whether early onset of menopause in HIV-infected women increases their risk of osteoporosis and heart disease requires further study.