Heiner C. Bucher

N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials

PURPOSE Observational studies have shown an inconsistent association between n-3 polyunsaturated fatty acids and the risk of coronary heart disease. We investigated the effects of dietary and non-dietary (supplemental) intake of n-3 polyunsaturated fatty acids on coronary heart disease. SUBJECTS AND METHODS We searched the literature to identify randomized controlled trials that compared dietary or non-dietary intake of n-3 polyunsaturated fatty acids with a control diet or placebo in patients with coronary heart disease. Studies had to have at least 6 months of follow-up data, and to have reported clinical endpoint data. We identified 11 trials, published between 1966 and 1999, which included 7951 patients in the intervention and 7855 patients in the control groups. RESULTS The risk ratio of nonfatal myocardial infarction in patients who were on n-3 polyunsaturated fatty acid-enriched diets compared with control diets or placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.2, P = 0.16; Breslow-Day test for heterogeneity, P = 0.01), and the risk ratio of fatal myocardial infarction was 0.7 (95% CI: 0.6 to 0.8, P <0.001; heterogeneity P >0.20). In 5 trials, sudden death was associated with a risk ratio of 0.7 (95% CI: 0.6 to 0.9, P <0.01; heterogeneity P >0.20), whereas the risk ratio of overall mortality was 0.8 (95% CI: 0.7 to 0.9, P <0.001; heterogeneity P >0.20). There was no difference in summary estimates between dietary and non-dietary interventions of n-3 polyunsaturated fatty acids for all endpoints. CONCLUSION This meta-analysis suggests that dietary and non-dietary intake of n-3 polyunsaturated fatty acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease.

Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial

CONTEXT In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs). OBJECTIVE To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes. DESIGN, SETTING, AND PATIENTS A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008. INTERVENTION Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based. MAIN OUTCOME MEASURES Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics. RESULTS The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%). CONCLUSION In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN95122877.

Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials

Objective To quantify the overall effects of bariatric surgery compared with non-surgical treatment for obesity. Design Systematic review and meta-analysis based on a random effects model. Data sources Searches of Medline, Embase, and the Cochrane Library from their inception to December 2012 regardless of language or publication status. Eligibility criteria Eligible studies were randomised controlled trials with ≥6 months of follow-up that included individuals with a body mass index ≥30, compared current bariatric surgery techniques with non-surgical treatment, and reported on body weight, cardiovascular risk factors, quality of life, or adverse events. Results The meta-analysis included 11 studies with 796 individuals (range of mean body mass index at baseline 30-52). Individuals allocated to bariatric surgery lost more body weight (mean difference −26 kg (95% confidence interval −31 to −21)) compared with non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 22.1 (3.2 to 154.3) in a complete case analysis; 5.3 (1.8 to 15.8) in a conservative analysis assuming diabetes remission in all non-surgically treated individuals with missing data) and metabolic syndrome (relative risk 2.4 (1.6 to 3.6) in complete case analysis; 1.5 (0.9 to 2.3) in conservative analysis), greater improvements in quality of life and reductions in medicine use (no pooled data). Plasma triglyceride concentrations decreased more (mean difference −0.7 mmol/L (−1.0 to −0.4) and high density lipoprotein cholesterol concentrations increased more (mean difference 0.21 mmol/L (0.1 to 0.3)). Changes in blood pressure and total or low density lipoprotein cholesterol concentrations were not significantly different. There were no cardiovascular events or deaths reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15% of individuals undergoing malabsorptive bariatric surgery) and reoperations (8%). Conclusions Compared with non-surgical treatment of obesity, bariatric surgery leads to greater body weight loss and higher remission rates of type 2 diabetes and metabolic syndrome. However, results are limited to two years of follow-up and based on a small number of studies and individuals. Systematic review registration PROSPERO CRD42012003317 (www.crd.york.ac.uk/PROSPERO).

Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

Objective To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions. Design Systematic review and meta-regression analysis of randomised controlled trials. Data sources Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field. Study selection In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months. Data extraction and synthesis Using standardised, pre-piloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated. Results The meta-regression analysis included 108 randomised trials involving 299 310 participants at risk of cardiovascular events. All analyses that adjusted for changes in low density lipoprotein cholesterol showed no association between treatment induced change in high density lipoprotein cholesterol and risk ratios for coronary heart disease deaths, coronary heart disease events, or total deaths. With all trials included, change in high density lipoprotein cholesterol explained almost no variability (<1%) in any of the outcomes. The change in the quotient of low density lipoprotein cholesterol and high density lipoprotein cholesterol did not explain more of the variability in any of the outcomes than did the change in low density lipoprotein cholesterol alone. For a 10 mg/dl (0.26 mmol/l) reduction in low density lipoprotein cholesterol, the relative risk reduction was 7.2% (95% confidence interval 3.1% to 11%; P=0.001) for coronary heart disease deaths, 7.1% (4.5% to 9.8%; P<0.001) for coronary heart disease events, and 4.4% (1.6% to 7.2%; P=0.002) for total deaths, when adjusted for change in high density lipoprotein cholesterol and drug class. Conclusions Available data suggest that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronary heart disease events, coronary heart disease deaths, or total deaths. The results support reduction in low density lipoprotein cholesterol as the primary goal for lipid modifying interventions.

Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care.

BACKGROUND Acute respiratory tract infections are the most common reason for antibiotic therapy in primary care despite their mainly viral etiology. A laboratory test measuring procalcitonin levels in blood specimens was suggested as a tool to reduce unnecessary prescribing of antibiotics. We consider whether antibiotic therapy guided by procalcitonin reduces the use of antibiotics without increasing the restrictions experienced by patients by more than 1 day. METHODS Fifty-three primary care physicians recruited 458 patients, each patient with an acute respiratory tract infection and, in the physicians opinion, in need of antibiotics. Patients were centrally randomized to either a procalcitonin-guided approach to antibiotic therapy or to a standard approach. For patients randomized to procalcitonin-guided therapy, the use of antibiotics was more or less strongly discouraged (procalcitonin level, < or =0.1 or < or =0.25 microg/L, respectively) or recommended (procalcitonin level, >0.25 microg/L). Follow-up data were collected at 7 days by treating physicians and at 14 and 28 days by blinded interviewers. RESULTS Adjusted for baseline characteristics, the mean increase at 14 days in days in which activities were restricted was 0.14 with procalcitonin-guided therapy (95% confidence interval [CI], -0.53 to 0.81 days), which met our criterion of an increase in days in which activities were restricted by no more than 1 day. With procalcitonin-guided therapy, the antibiotic prescription rate was 72% lower (95% CI, 66%-78%) than with standard therapy. Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days (adjusted odds ratio, 1.0 [95% CI, 0.7-1.5]). CONCLUSIONS As an adjunct to guidelines, procalcitonin-guided therapy markedly reduces antibiotic use for acute respiratory tract infections in primary care without compromising patient outcome. In practice, this could be achieved with 1 to 2 procalcitonin measurements in patients for whom the physician intends to prescribe antibiotics.

Percutaneous transluminal coronary angioplasty versus medical treatment for non-acute coronary heart disease: meta-analysis of randomised controlled trials

Abstract Objective: To determine whether percutaneous transluminal coronary angioplasty (angioplasty) is superior to medical treatment in non-acute coronary artery disease. Design: Meta-analysis of randomised controlled trials. Setting: Randomised controlled trials conducted worldwide and published between 1979 and 1998. Participants: 953 patients treated with angioplasty and 951 with medical treatment from six randomised controlled trials, three of which included patients with multivessel disease and pre-existing myocardial infarction. Main outcome measures: Angina, fatal and non-fatal myocardial infarction, death, repeated angioplasty, and coronary artery bypass grafting. Results: In patients treated with angioplasty compared with medical treatment the risk ratios were 0.70 (95% confidence interval 0.50 to 0.98; heterogeneity P<0.001) for angina; 1.42 (0.90 to 2.25) for fatal and non-fatal myocardial infarction, 1.32 (0.65 to 2.70) for death, 1.59 (1.09 to 2.32) for coronary artery bypass graft, and 1.29 (0.71 to 3.36; heterogeneity P<0.001) for repeated angioplasty. Differences in the methodological quality of the trials, in follow up, or in single versus multivessel disease did not explain the variability in study results in any analysis. Conclusions: Percutaneous transluminal coronary angioplasty may lead to a greater reduction in angina in patients with coronary heart disease than medical treatment but at the cost of more coronary artery bypass grafting. Trials have not included enough patients for informative estimates of the effect of angioplasty on myocardial infarction, death, or subsequent revascularisation, though trends so far do not favour angioplasty.

Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials.

OBJECTIVES To evaluate the efficacy of isoniazid for the prevention of tuberculosis in tuberculin skin test-positive and negative individuals with HIV infection. DESIGN Meta-analysis of randomized controlled trials. SETTING Seven trials from Mexico, Haiti, the United States, Zambia, Uganda and Kenya. PATIENTS Individuals free from tuberculosis, 2367 persons in the intervention and 2162 in the control groups. INTERVENTION Comparison of isoniazid with placebo or no prophylaxis. METHODS A systematic search of the literature was carried out from 1985 to October 1997 for randomized controlled trials of isoniazid prophylaxis in HIV-infected persons. Two reviewers evaluated the relevance of each candidate study and the validity of eligible trials. Studies were pooled using a random effect model, conducting secondary analyses for tuberculin skin test-positive and negative persons. RESULTS Mean follow-up in trials varied between 0.4 and 3.2 years. Pooling all seven trials, a risk ratio was found for persons treated with isoniazid for developing tuberculosis of 0.58 [95% confidence interval (CI), 0.43-0.80] and 0.94 (95% CI, 0.83-1.07) for death. In groups of tuberculin skin test-positive and negative persons, the risk ratio of tuberculosis was 0.40 (95% CI, 0.24-0.65) and 0.84 (95% CI, 0.54-1.30), respectively, and the difference in the effectiveness of isoniazid versus placebo between these groups was statistically significant (P = 0.03, for the difference of summary estimates). Consistency of results was found across trials (P > 0.10, heterogeneity value) for all comparisons. CONCLUSIONS Prophylaxis with isoniazid reduces the risk of tuberculosis in persons with HIV infection. The effect is restricted to tuberculin skin test-positive persons.

Effect of HMGcoA Reductase Inhibitors on Stroke: A Meta-Analysis of Randomized, Controlled Trials

Stroke is one of the leading causes of death, long-term disability, and hospital admission in the industrialized world [1]. Several risk factors for stroke have been identified, including age, hypertension, diabetes, and cigarette smoking [2]. The relation between cholesterol levels and risk for stroke is less clear. In several epidemiologic studies [3, 4], the incidence of thromboembolic stroke increased with elevated cholesterol levels but a J-shaped association was seen because of an increased risk for hemorrhagic stroke at low cholesterol levels. A large review of prospective cohort studies [5] found no association between cholesterol levels and stroke, although the misclassification of different types of stroke in several of the reviewed studies may have biased the overall estimate. Cholesterol-lowering drugs reduce the incidence of nonfatal and fatal myocardial infarction in primary and secondary prevention [6, 7]. Whether cholesterol-lowering interventions affect the incidence of stroke remains uncertain. A meta-analysis of randomized trials found no reduction in stroke-related morbidity or mortality rates, but this review did not include more recent trials that used HMGcoA reductase inhibitors (3-hydroxy-3-methylglutaryl coenzyme A) [8]. We conducted a systematic review of randomized, controlled trials to assess the efficacy of HMGcoA reductase inhibitors compared with the efficacy of other cholesterol-lowering interventions to reduce the incidence of stroke. Methods We did a systematic search of the MEDLINE and EMBASE databases and previously published meta-analyses [9-14]. We searched the reference lists of identified papers for citations to additional relevant articles, and we identified all randomized, controlled trials published through October 1996 that compared dietary or pharmaceutical cholesterol-lowering interventions with placebo or usual diet. We considered studies to be eligible for our meta-analysis if they randomly assigned participants to active treatment or placebo and reported the occurrence of nonfatal and fatal strokes. We included trials regardless of whether they focused on primary or secondary prevention of coronary heart disease and regardless of whether they used unifactorial or multifactorial interventions. We excluded trials that were restricted to patients who had previously had stroke because these trials provided insufficient data on the underlying pathophysiologic cause of stroke and therefore had study samples that were too heterogenous. We also excluded trials of cholesterol-lowering interventions in heart transplant recipients [15]. We did not consider transischemic attacks as study end points because they were of limited importance and because consistent criteria for ascertainment across trials were lacking. We assessed the methodologic quality of included trials with respect to the following variables: 1) proportion of participants with complete followup, 2) concealment of randomization, 3) blinding of patients and caregivers, and 4) blinding for outcome assessment. We created a dichotomous variable for each of the four quality variables and added scores to yield a summary scale ranging from 0 to 4, with 0 as the lowest and 4 as the highest quality score. Because too few studies reported data on death from stroke, we combined fatal and nonfatal strokes into a single category. To pool treatment effects across studies, we calculated a weighted average risk ratio of all outcomes in the treatment and control groups by using a random-effects model [16]. We tested for heterogeneity with the Breslow-Day test [17]. Because a previous meta-analysis (Bucher and colleagues. In preparation) suggested that HMGcoA reductase inhibitors had a greater beneficial effect than other antilipidemic interventions on major morbidity and mortality, we examined the effects of major drug classes separately. However, for completeness of data presentation, we report overall estimates and results of overall tests of heterogeneity. We tested the difference in combined estimates of intervention type and used the z-score for each type of intervention by dividing the difference in the subgroup summary log relative risk by the SE of the difference. We grouped trials into four categories: trials of HMGcoA reductase inhibitors (n = 8 [6, 7, 18-23]), trials of fibrates (n = 5 [24-28]), trials of resins (n = 3 [29-31]), and trials of dietary interventions (n = 10 [31-40]). Five trials studied niacin [25], the combination of niacin and clofibrate [41], hormones [42-44], fish oil [45], and ileal bypass surgery [46]. Data Synthesis We identified 64 randomized, controlled trials that reported data on mortality. Of these 64 trials, 30 provided data on the incidence of nonfatal and fatal stroke. Two trials were excluded because they studied patients who had previously had stroke [47-49]; this left 28 trials for analysis. Two of these 28 trials had multiple treatment arms [25, 26, 42-44]. In total, the intervention group consisted of 49 477 patients and the control group consisted of 56 636 patients. Table 1 and (Table 3) describes the 28 included trials. Table 1. Randomized, Controlled Trials on the Effects of Cholesterol-Lowering Treatment on the Incidence of Nonfatal and Fatal Stroke* Table 3. Table 1 Continued Nonfatal and Fatal Stroke The risk ratio for nonfatal and fatal stroke for all 28 trials was 0.95 (95% CI, 0.86 to 1.05; test of heterogeneity, P > 0.2) (Table 2). For HMGcoA reductase inhibitors, the risk ratio for nonfatal and fatal stroke was 0.76 (CI, 0.62 to 0.92; test of heterogeneity, P > 0.2) (Figure 1). This estimate was statistically significantly different (P = 0.01) from the summary estimate for all other cholesterol-lowering interventions (risk ratio, 1.02 [CI, 0.91 to 1.15]). Pooled estimates for fibrates (risk ratio, 1.12 [CI, 0.84 to 1.48]; test of heterogeneity, P > 0.2), resins (risk ratio, 1.07 [CI, 0.57 to 2.00]; test of heterogeneity, P > 0.2), and dietary interventions (risk ratio, 0.98 [CI, 0.82 to 1.18]; test of heterogeneity, P > 0.2) suggested that these interventions had no effect on the incidence of nonfatal and fatal stroke. Table 2. Effects of Cholesterol-Lowering Interventions, Stratified by Type of Intervention, on Nonfatal and Fatal Stroke, Death from Coronary Heart Disease, and Overall Mortality* Figure 1. Risk ratio and summary estimates with 95% CIs for nonfatal and fatal stroke in randomized, controlled trials comparing HMGcoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors with placebo. P Death from Coronary Heart Disease and Overall Mortality For death from coronary heart disease; the risk ratio for all trials was 0.87 (CI, 0.79 to 0.94; test of heterogeneity, P = 0.003). With HMGcoA reductase inhibitors, the risk ratio was 0.69 (CI, 0.59 to 0.80; test of heterogeneity, P > 0.2); this was significantly different from the risk ratio for all other trials of cholesterol-lowering interventions (risk ratio, 0.90 [CI, 0.83 to 0.98]) (P = 0.003 for the difference). For groupings of fibrates, resins, and dietary interventions, risk ratios for death from coronary heart disease showed no statistically significant reduction of coronary heart disease mortality. The risk ratio for overall mortality was 0.94 (CI, 0.84 to 1.06; test of heterogeneity, P < 0.001). With HMGcoA reductase inhibitors, the risk ratio for death from all causes was 0.80 (CI, 0.71 to 0.90; test of heterogeneity, P > 0.2); this was statistically significantly different from the risk ratio for death from all causes with all other cholesterol-lowering interventions (risk ratio, 0.97 [CI, 0.86 to 1.10]) (P = 0.03 for the difference). Discussion This systematic review shows that decreasing cholesterol levels with HMGcoA reductase inhibitors reduces the risk for nonfatal and fatal stroke. Our inference that this class of drugs results in larger reductions in the incidence of nonfatal and fatal strokes compared with other antilipidemic interventions is strong [50]. The reasons for this include the fact that our hypothesis about differential drug class effects preceded our analysis and was the only subgroup analysis tested. The difference between the summary estimates for HMGcoA reductase inhibitors and the summary estimates for other cholesterol-lowering interventions is moderate, clinically important, and statistically significant. The treatment effect of HMGcoA reductase inhibitors was consistent across studies. Furthermore, HMGcoA reductase inhibitors are more potent in their cholesterol-lowering effect than are older drugs. This provides a biological rationale for their greater effect with respect to risk for stroke. Our findings should nevertheless be regarded with some caution. Our evaluation of HMGcoA reductase inhibitors relative to other cholesterol-lowering interventions is based on between-study rather than within-study treatment comparisons. Differences in efficacy that are apparently due to treatment, when inferred from between-study comparisons, may actually be due to other factors, including differences in study design or populations. For example, on average, study participants in trials of HMGcoA reductase inhibitors were older and had higher event rates for nonfatal and fatal strokes compared with participants in trials of other interventions. This may explain, at least in part, apparent differences between HMGcoA reductase inhibitors and other interventions. The results of the overall test for heterogeneity were not statistically significant, raising questions about the appropriateness of a subgroup analysis. Because of limitations in the power of overall tests of heterogeneity, however, important differences between subgroups may exist and yet not be evident [51]. The statistically significant difference between the effect of HMGcoA reductase inhibitors and the effect of other agents emphasizes the limitations of the overall test of heterogeneity. In addition, we made our decisio

Meta-Analysis Comparing Mediterranean to Low-Fat Diets for Modification of Cardiovascular Risk Factors

BACKGROUND Evidence from individual trials comparing Mediterranean to low-fat diets to modify cardiovascular risk factors remains preliminary. METHODS We systematically searched MEDLINE, EMBASE, Biosis, Web of Science, and the Cochrane Central Register of Controlled Trials from their inception until January 2011, as well as contacted experts in the field, to identify randomized controlled trials comparing Mediterranean to low-fat diets in overweight/obese individuals, with a minimum follow-up of 6 months, reporting intention-to-treat data on cardiovascular risk factors. Two authors independently assessed trial eligibility and quality. RESULTS We identified 6 trials, including 2650 individuals (50% women) fulfilling our inclusion criteria. Mean age of enrolled patients ranged from 35 to 68 years, mean body mass index from 29 to 35 kg/m(2). After 2 years of follow-up, individuals assigned to a Mediterranean diet had more favorable changes in weighted mean differences of body weight (-2.2 kg; 95% confidence interval [CI], -3.9 to -0.6), body mass index (-0.6 kg/m(2); 95% CI, -1 to -0.1), systolic blood pressure (-1.7 mm Hg; 95% CI, -3.3 to -0.05), diastolic blood pressure (-1.5 mm Hg; 95% CI, -2.1 to -0.8), fasting plasma glucose (-3.8 mg/dL, 95% CI, -7 to -0.6), total cholesterol (-7.4 mg/dL; 95% CI, -10.3 to -4.4), and high-sensitivity C-reactive protein (-1.0 mg/L; 95% CI, -1.5 to -0.5). The observed heterogeneity across individual trials could, by and large, be eliminated by restricting analyses to trials with balanced co-interventions or trials with restriction of daily calorie intake in both diet groups. CONCLUSION Mediterranean diets appear to be more effective than low-fat diets in inducing clinically relevant long-term changes in cardiovascular risk factors and inflammatory markers.

Correlates of self-reported nonadherence to antiretroviral therapy in HIV-infected patients: the Swiss HIV Cohort Study

Background: Adherence is one of the most crucial issues in the clinical management of HIV-infected patients receiving antiretroviral therapy (ART). Methods: A 2-item adherence questionnaire was introduced into the Swiss HIV Cohort Study in July 2003. All 3607 eligible patients were on ART for ≥6 months and their current regimen for ≥1 month. Three definitions of nonadherence were considered: missing ≥1 dose, missing ≥2 doses, and taking <95% of doses in the past 4 weeks. Results: Over 30% of patients reported missing ≥1 dose, 14.9% missed ≥2 doses, and 7.1% took <95% of doses in the previous 4 weeks. The rate of drug holidays was 5.8%. Whether using more or less conservative definitions of nonadherence, younger age, living alone, number of previous regimens, and boosted protease inhibitor regimens were independent factors associated with nonadherence. There was a significant association between optimal viral suppression and nonadherence as well as a significant linear trend in optimal viral suppression by missed doses. Conclusions: Younger age, lack of social support, and complexity of therapy are important factors that are related to nonadherence with ART. Investment in behavioral dimensions of HIV is crucial to improve adherence in ART recipients.