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Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial Rainer Weber1*, Lisanne Christen2, Stephan Christen2, Simone Tschopp3, Hansjoerg Znoj3, Christine Schneider1, Joachim Schmitt4, Milos Opravil1, Huldrych F Günthard1 and Bruno Ledergerber1, for the Swiss HIV Cohort Study5 1
Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich, Switzerland Arbeitsgemeinschaft Sozialwissenschaft & Gesundheitsforschung (ASG), Uetikon am See, Switzerland 3 Institute for Psychology, University of Bern, Bern, Switzerland 4 Studien- und Berufsberatung des Kantons Zürich, Zürich, Switzerland 5 Members are listed in Acknowledgements 2
*Corresponding author: Tel: +41 1 255 38 26; Fax: +41 1 255 32 91; E-mail:
[email protected]
Objective: A high level of adherence to antiretroviral therapy is required for complete suppression of HIV replication, immunological and clinical effectiveness. We investigated whether cognitive behaviour therapy can improve medication adherence. Design: Prospective randomized 1-year trial. Setting: Collaboration of HIV university outpatient clinic and psychotherapists in private practice. Participants: 60 HIV-infected persons on stable antiretroviral combination therapy and viral load below 50 copies/ml. Intervention: Cognitive behaviour intervention in individual patients, in addition to standard of care. Main outcome measures: Feasibility and acceptance of intervention; adherence to therapy assessed using medication event monitoring system (MEMS) and self-report questionnaire; virological failure; psychosocial measures. Results: The median number of sessions for cognitive behaviour intervention per patient during the 1-year trial
was 11 (range 2–25). At months 10–12, mean adherence to therapy as assessed using MEMS was 92.8% in the intervention and 88.9% in the control group (P=0.2); the proportion of patients with adherence ≥95% was 70 and 50.0% (P=0.014), respectively. While there was no significant deterioration of adherence during the study in the intervention arm, adherence decreased by 8.7% per year (P=0.006) in the control arm. No differences between the intervention group and standard of care group were found regarding virological outcome. Compared with the control group, participants in the intervention group perceived a significant improvement of their mental health during the study period. Conclusions: Cognitive behavioural support in addition to standard of care of HIV-infected persons is feasible in routine practice, and can improve medication adherence and mental health.
Introduction Antiretroviral combination therapy is effective with regard to suppression of viral replication, immunological and clinical outcome [14,36], but it is not potent enough to eradicate HIV, and does not target latent viruses effectively [9,17,51,56]. Among the most important prerequisites for treatment success is the patients’ adherence to therapy of at least 90–95%[43]. Failure to control HIV replication can result in clinical progression. Furthermore, viral resistance can develop when organisms in plasma or tissue are exposed to drug levels that are insufficient to stop their replication completely. Drug resistance may hamper future treatment options of an individual and can have a public health impact ©2004 International Medical Press 1359-6535/02/$17.00
because resistant organisms can be transmitted to other individuals [37,57]. Adherence to drug therapy that is good enough to reach and maintain the therapeutic goal in a chronic and incurable illness is demanding for patients. Numerous predictors of adherence have been recognized, including physician–patient communication [47,48], organizational aspects of care settings and patient characteristics (emotional issues, health status, sociodemographic and behavioural variables, and recreational drug use), as well as mode of drug regimen (number of pills, dosing frequency and adverse events of treatment) [40,53]. However, the fundamental precondition for initiation and maintenance of drug 85
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therapy is the patient’s motivation, that is, his or her readiness for a behaviour change [45]. Maintaining long-term treatment can particularly be challenging when the treatment course develops other than expected, when drug adverse events occur or in case the illness deteriorates despite treatment. Current approaches to supporting medication adherence for chronic health problems are complex and labour-intensive, and evidence for efficacy of specific interventions is limited [19,24,26,27,41]. Most successful interventions employed several modalities addressing cognitive, behavioural and affective components [1]. The conceptual models integrating variables associated with adherence to therapy emphasize interdisciplinary collaboration. Also, care needs to involve different support systems including healthcare providers, social support networks, family and friends [53]. We sought to study whether medical care of HIVinfected persons can be complemented by psychotherapy. The objectives of our 1-year randomized pilot trial were: (i) to investigate whether a cognitive behaviour intervention in individual patients on antiretroviral combination therapy was feasible and accepted by patients; and (ii) to study whether the intervention was effective with regard to improved adherence to therapy, virological outcome and patients’ mental health.
Methods Study design, selection of participants This is a prospective controlled 12 months pilot trial of 60 HIV-infected persons on antiretroviral therapy who were 1:1 randomized to receive standard of care or standard of care plus individual cognitive behaviour intervention. Inclusion criteria were therapy containing a combination of at least three different antiretroviral drugs of at least two different drug classes, viral load below 50 copies/ml documented within the previous 3 months and at screening visit, participation in the Swiss HIV cohort study [36], no intravenous drug use or on stable methadone maintenance in case of drug addiction. Ethical committee approval was obtained and all participants gave written informed consent. Primary end-point was the proportion of patients with viral load ≤50 copies/ml at 1 year. Secondary endpoints were adherence to therapy assessed using electronic drug exposure monitoring and by patients’ self-report, and psychosocial measures. The allocation schedule for two treatment arms and three different CD4 strata (0–0.05×109/l, 9 9 0.051–0.2×10 /l or >0.2×10 /l) with randomly permuted block sizes of 2 and 4, was generated in 86
advance with the program RANCODE V 3.0 (IDV Datenanalyse und Versuchsplanung, Gauting, Germany) and properly concealed from care providers.
Healthcare providers and psychotherapists Standard of care as well as study consultations for an individual patient were provided by six fellow physicians at the University Hospital HIV outpatient clinic, Zurich, Switzerland, who were supervised by staff physicians specialized in infectious diseases. A visit lasted on average approximately 30 min; enrolment visit was longer. A single study nurse who saw patients at each visit was responsible for collection of clinical and laboratory data, psychometric data and monthly download of the data collected by the electronic drug exposure monitoring system. The intervention was provided for individual patients by 10 different licensed psychotherapists in private practice who had a university degree and formal training in cognitive behaviour therapy, including one MD and nine psychologists. They had regular supervisions in two different groups. All psychotherapists had a 2 h lecture on principles of antiretroviral therapy prior to the study.
Intervention After randomization, study participants in the intervention arm received the address of one of the psychotherapists and were asked to schedule by themselves a first appointment. The allocation of participants to psychotherapists was at random, based on the availability of the psychotherapists who indicated the number of participants they would care for prior to the start of the study. The frequency of appointments with the psychotherapists was not predetermined by the study protocol but was worked out by participants and psychotherapists during the course of the study. The protocol defined a minimum of three and a maximum of 25 sessions within the 1-year study period. An intervention lasted 45 min on average. The participants were informed that the study was not proposed because the physicians providing care felt that there was a psychological problem or a psychiatric disease to address but rather to support adherence to drug therapy using techniques of cognitive behaviour therapy, provided by specialists in this field. The psychotherapists were instructed to define at first visit, together with the participants, at least two goals for future interventions. At least one of the goals had to be related to medication adherence, but participants and psychotherapists were free to identify additional goals not related to anti-HIV therapy. The method of intervention had to be based on concepts of cognitive behaviour therapy [3,4]. ©2004 International Medical Press
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Measures Clinical and laboratory assessments Demographic characteristics and HIV-related clinical and laboratory data were assessed at baseline. Followup included monthly visits for 12 months with assessments of clinical and laboratory data, course of treatment, drug adverse events and HIV-1 RNA (boosted Amplicor HIV-1 Monitor Test, version 1.5, Roche Diagnostic Systems, Muttenz, Switzerland; modified according [50]). The CD4 lymphocyte count was measured every 3 months. After study end, prospective follow-up of participants continued with 6 monthly visits according to the protocol of the Swiss HIV Cohort Study [36]. Medication adherence monitoring [10] Adherence was assessed both in the control and intervention group using the electronic medication exposure monitoring system (MEMS) (eDEM, Aardex Ltd, Zug, Switzerland). The study nurse downloaded the data monthly to a central database in the presence of the participants, to whom their individual performance was shown on screen as a graphic depicting the times of opening the pill boxes during the previous month. We used the measurements during the first month of the study to approximate baseline values. Self-reported adherence to therapy Using a structured questionnaire participants were asked at baseline and at monthly follow-up visits to indicate on visual analogue Likert scales ranging from 0 (never) to 10 (always) whether they had taken the antiretroviral drugs correctly as prescribed: (a) during the previous 7 days; and (b) during the previous 24 h, for each of the three items: (1) drug taken; (2) dose interval correct; and (3) consideration of food restrictions, if required. Psychosocial measures Three structured and standardized questionnaires were used at baseline and at month 12: (i) Self-Report Symptom Inventory SCL-90 [11,12] (German translation) to measure nine symptoms of psychopathology (for example, depression, anxiety), overall psychological distress, intensity of symptoms and the number of self-reported symptoms; (ii) a scale to assess ways of coping with disease (original German version: Trierer Skalen zur Krankheitsbewältigung) [15,16,34]; and (iii) a health locus of control scale (original German version: Fragebogen zur Erhebung von Kontrollüberzeugungen zu Krankheit und Gesundheit) [39] to assess health-related behaviours and beliefs [49,54]. A computer program immediately evaluated Antiviral Therapy 9:1
baseline measurements after the visit and the results transferred to the psychotherapists. A structured and standardized ‘Questionnaire on experience and behaviour’ (original German version: Veränderungsfragebogen des Erlebens und Verhaltens [7,58], modified by [55]) was used at months 6 and 12 in order to assess changes of mental state and behaviour as perceived by participants themselves during the study period compared with the pre-study period. The questionnaire (see appendix) consisted of 27 bipolar items on a seven-step visual analogue Likert scale (such as, ‘I am more relaxed’ versus ‘I am more tense’; ‘I am better able’ versus ‘I am less able to cope with the difficulties of everyday life’). The total score of change is indicative of the bipolar states ‘quietness, confidence, optimism’ versus ‘stress, uncertainty, pessimism’. Documentation of cognitive behaviour intervention Psychotherapists kept a record on qualitative information and used: (i) The Goal Attainment Scaling used to identify intervention goals [32]; (ii) a structured 32-item patient questionnaire (Berner Patientenstundenbogen) [22]; and (iii) a structured 52-item therapists’ questionnaire (Berner Therapeutenstundenbogen) [22].
Statistics Statistics were performed using non-parametric methods for comparisons of independent samples (that is, group comparisons using χ2 and Wilcoxon ranksum tests) and dependent samples (that is, repeated measures using Mc Nemar and Wilcoxon tests, Friedman analyses of variance). To identify time-trends in adherence as measured by MEMS we calculated individual slopes for each patient using linear regression. We then tested whether slopes of adherence over time in patients from intervention and control groups differed from each other (Wilcoxon rank-sum test) or whether they differed from zero (Wilcoxon signedranks test). Kaplan-Meier curves and logrank-tests were applied to analyse the time to virological rebound, defined as date of the first of two subsequent viral load determinations above 400 copies/ml.
Results Patient characteristics A total of 32 patients (eight female) were randomized in the intervention and 28 patients (two female) in the control group. Patients’ demographic characteristics, education, clinical status as well as treatment history between the study groups did not differ (Table 1). Their median age was 41 years; a third had a history of previous AIDS. Median CD4 lymphocyte nadir (that is, lowest value ever) was 173 and 120 cells/µl in the intervention and control group, median peak HIV-1 RNA 87
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Table 1. Patient characteristics at baseline
Number of randomized patients (%)* Number of female (%) Median age (range), years Men who have sex with men, number (%) Heterosexual mode of HIV acquisition Previous intravenous drug use † In opiate substitution programme Other mode of HIV acquisition Education, number (%) Mandatory school only Finished apprenticeship Higher education Earn his/her living, number (%) From professional work From insurances (excluding insurance for unemployment) From savings or other sources ‡ HIV infection Number with prior AIDS (%) Baseline CD4 lymphocytes/µl, median (range) Nadir of CD4 lymphocytes/µl, median (range) Baseline HIV-1 RNA copies/ml, median (range) Peak HIV-1 RNA copies/ml, median (range) § Days since first HIV-1 RNA 0.05). † No current intravenous drug use. ‡ None of them from unemployment insurance or from relatives. § Viral load was not available for all patients before initiation of antiretroviral therapy because some of them started treatment before virological assessment was routinely available. Thus, we do not have the ‘real’ peak viral load available for all patients. ¥ Ritonavir-boosted PI regimen is ‘single PI’. No double PI and no triple RTI regimens were used in patients in this trial. ¢ Values reflect mean score results ±standard deviation; tests of significance showed no differences between time points (all P>0.05). bld, below level of detection; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
was 69 040 and 34 898 copies/ml, respectively. Both groups were a median of approximately 3.5 years on any antiretroviral drugs, a median of 3 years on potent 88
combination therapy, and the median time since first HIV-1 RNA below the level of detection was 2.5 years. At baseline, 81.3% of participants in the intervention ©2004 International Medical Press
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and 85.7% in the control arm, respectively, were on a single protease inhibitor-containing triple combination regimen.
stopped antiretroviral therapy intermittently or definitively during follow-up in the Swiss HIV Cohort Study had sustained virological suppression exceeding the end of the controlled trial.
Study visits and interventions A total of 29 (93.5%) participants in the intervention arm and 24 (88.9%) the control arm, respectively, completed the trial. Participants in the intervention group had a median of 11 (range 2–25) cognitive behaviour interventions with the psychotherapists, three participants (10%) had less than three, approximately 50% had on average more than 10 session (Table 2).
Virological and immunological outcome Only three patients had a viral load above 50 copies/ml at month 12, one in the intervention and two in the control group, respectively. In each study arm, nine patients each had intermittently a viral load above 50 copies/ml (‘blip’), which mostly returned to levels below 50 copies/ml at time of next measurement (Table 2) as observed before [23,25]. The probability to develop viral rebound after the trial, defined as at least two consecutive viral load measurements above 400 copies/ml, was similar in both groups. In both study arms, patients who never
Adherence to therapy Adherence assessments at baseline were not different between the two study arms: self-reported mean adherence was 9.97 in the intervention and 9.92 in the control arm (P=0.4); adherence as assessed using MEMS was 94.3 and 94.9% (P=0.2) during month 1; and the proportion of participants with adherence ≥95% was 82.1 and 69.6%, respectively, during month 1 (P=0.29) (Figure 1). During the trial, mean medication adherence, as assessed using MEMS, remained stable in the intervention group (month 1, 94.3% versus month 10–12, 92.8%) with average individual slopes of adherence over time of –3.0% per year (not significantly different from zero, P=0.14). In contrast, medication adherence decreased in the control group during the 1-year study from a mean of 94.3% at month 1 to 88.9% at month 10–12, and the individual slopes of adherence were –8.7% (significantly differing from zero, P=0.006) (Figure 1, panel A). There was, however, no significant difference between the slopes of intervention and
Table 2. Course of study, virological and immunological end-points
Number of participants (%)* Randomized Erroneously randomized Drop out at randomization Started study Drop out Death Completed Number of psychotherapeutic visits, median (range) 10 Virological end-points (HIV-1 RNA), number of patients (%) Below the level of detection 0–50 copies/ml >50 copies/ml Intermittent values >50 copies/ml (‘blips’) CD4 lymphocyte end-points Median (range) Number of participants with increase of at least 50 cells/µl Number of participants with decrease of at least 50 cells/µl Change of antiretroviral therapy during study Number of patients Number who stopped therapy (%)
Intervention
Control
32 1
28
31 (100) 1 1 29 (93.5) 11 (2-25) 3 (9.7) 5 (16.1) 6 (19.4) 17 (54.8)
1 27 (100) 3 0 24 (88.9) not applicable
21 (72.4) 6 (20.7) 2 (6.9) 9 (31.0)
19 (79.2) 4 (16.7) 1 (4.2) 9 (37.5)
407.5 (203–955) 17 (58.6) 3 (10.3)
490 (95–1796) 16 (66.7) 2 (8.3)
5 (17.2) 1 (3.4)
3 (12.5) 1 (4.2)
*No significant differences between intervention and control group regarding all variables in table (all P>0.05).
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100 95 Daily dose 90 85 Intervention Control
80
0–1 2–3 4–6 Months
Mean (SEM) weekly adherence (%)
B 100
7–9 10–12
D
Morning dose
95 90
Evening dose
85 80
Intervention Control 0–1 2–3 4–6 Months
Adherence (visual analogue scale)
C Mean (SEM) weekly adherence (%)
A
% of patients with ≥95% monthly adherence
Figure 1. Adherence to therapy of the intervention versus control group
100 95
Daily dose
90 85
Intervention Control 0–1 2–3 4–6 Months
7–9 10–12
10.0 9.8 9.8 9.7 9.6 9.5
7–9 10–12
Intervention Control Baseline 1–3 4–6 Months
7–9 10–12
(A–C) Depict the results of the medication event monitoring system: (i) mean weekly adherence of all daily doses (SEM, standard error of the mean); (ii) mean weekly adherence of morning and evening dose; (iii) proportion of patients with monthly adherence equal or above 95%. (D) Self report of adherence to correct daily doses within the previous 7 days, assessed using a Likert visual analogue scale (see statistical comparison in result section).
control arms (P=0.15). Using Wilcoxon matched-pairs signed-ranks test the average morning adherence was significantly superior to the evening adherence (all patients, P=0.0001; intervention, P=0.0009; control, P=0.017) (Figure 1, panel B). The proportion of patients with monthly adherence ≥95% at months 10–12 was 70.8% in the intervention and 50.0% in the control arm (P=0.014), respectively (Figure 1, panel C). Whereas self-reported mean overall adherence was similar at baseline, average scores in the intervention arm were significantly superior to the control arm during follow-up (9.93 and 9.80 at months 10–12, P=0.012) (Figure 1, panel D). With regard to the accuracy of drug intake, the self-reported adherence to overall drug intake was best, whereas correct timing of drug intake and adherence to food restrictions appeared to be more difficult for patients (data not shown).
self-report symptom inventory indicate that our study population was in relatively good health when compared with a reference population in Continental Europe [20] and was significantly healthier compared with HIV-infected persons who were examined in Germany in 1992 before antiretroviral combination therapy was available [21]. The patients’ perception of his or her changes of mental state and behaviour during the study period showed significant differences between participants in the intervention and in the control arm, respectively. Particularly, we found that participants who had 10 or more cognitive behaviour interventions during the 1year study period had a more prominent perception of improvement at study end (Figure 2). Data on the psychotherapists’ and patients’ evaluation of the intervention will be reported elsewhere.
Psychosocial measures
Cognitive behaviour intervention in addition to standard of care, with the aim of improving adherence to antiretroviral combination therapy, was feasible with regard to practicability, acceptance by patients, and collaboration between physicians and psychotherapists. The median number of psychotherapeutic
The coping with disease scale, the health locus of control scale and the self-reported symptom inventory showed neither differences between participants of the two study arms at baseline (Table 1), nor significant changes during the study period. The results of the 90
Discussion
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Figure 2. Patients’ perception of changes of mental health and behaviour at month 6 compared to baseline, and at month 12 compared to baseline
Score of change
P=0.0045 P=0.0023
P=0.031
200 180 160 140 120 100 80 60
Month
6
Group
Control all
12
6
12
Intervention all
6
12
Intervention ≤10 sessions
6
12
Intervention >10 sessions
Assessed using the ‘questionnaire on experience and behaviour’ (the higher the score, the higher is the perceived change for the better) [7,55,58].
interventions per patient during the 1-year study was 11 (range 2–25), causing median costs of 1760.00 Swiss Francs per patient per year (1250.00 US Dollars; approximately equal to the costs of a 1-month supply of a standard antiretroviral triple combination drug regimen). We achieved an improved maintenance of adherence to therapy in the intervention group compared with the control group as assessed using electronic drug exposure monitoring. Furthermore, compared with the control groups, participants in the intervention group perceived an improvement of their mental health and behaviour during the 1-year study period. This improvement correlated with the number of sessions, that is, patients with 10 or more consultations with the psychotherapists reported a more pronounced change for the better compared with those who had fewer consultations. We found no differences between the intervention group and control group regarding virological outcome and changes of psychosocial measures. This may, in part, be explained by the fact that – compared with other data on adherence to antiretroviral therapy – both our control and intervention group had high rates of adherence, possibly due to the frequency of monthly clinical visits during the study period, sufficient physician time available per patient (30 min per visit, which is the standard for all patients at our clinic, also when not enrolled in studies), and good mental and physical health status. Furthermore, all participants of the control as well as intervention group used electronic drug exposure monitoring (MEMS). The system itself may be considered an intervention possibly confounding the analysis of the effect of cognitive behaviour therapy on virological end-points. However, we had to use MEMS as the gold standard of objective adherence measurement [10] because it is more sensitive and specific than self-reporting, pill Antiviral Therapy 9:1
counts, physicians’ estimation of adherence or other methods, and it strongly correlates with virological outcome [2,29–31,43]. We found a rather large discrepancy between self-report on adherence and data of electronic drug monitoring. As observed by others, patient self-report tends to overestimate adherence [6,38,42,43]. This was a randomized controlled trial using procedures that appear to be applicable in routine practice. Our study participants were representative for our outpatient clinic: a third had a history of previous AIDS, their median CD4 lymphocyte nadir was below 200 cells/µl, and they were a median of 3.5 years on antiretroviral therapy. We intentionally involved 10 different psychotherapists in private practice, who had no special training or previous experience in the care of HIV-infected individuals in order to reproduce a trial design comparable with routine care. A further strength of the study design was that cognitive behaviour intervention was offered to the individual, in contrast to group intervention that possibly would not have been accepted by many patients and probably would focus less on personal needs of patients. Furthermore, we decided to investigate the effect of cognitive behaviour therapy because its methods have documented evidence for efficacy, are standardized and inter-therapists’ reliability is high [5,13,28]. Limitations of our pilot study are the relatively small number of study participants and the study period of 1 year for an infection that, at the present stage, requires years long, possibly lifelong continuous or intermittent drug therapy. We may have selected patients who were particularly adherent to therapy but we intentionally chose the inclusion criteria of stable HIV-1 RNA levels below 50 copies/ml at enrolment because the small pilot trial required a homogenous patient group with little virological variation. Therefore, the focus of our investigation was rather maintenance than achievement of 91
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adherence to therapy. Adherence is a time-dependent variable and may frequently drop during the maintenance phase, also among patients who had good adherence during the induction phase [18]. Although we expect that cognitive behaviour intervention may even be more helpful for patients who initiate treatment, we cannot formally prove this hypothesis with our data. This is the first controlled trial to offer individual cognitive behaviour intervention with the aim of optimizing antiretroviral therapy. Although its effect appears small, it may be clinically most relevant because adherence was maintained around 95% in the intervention group at month 12, whereas a decrease to values below 90% was observed in the control group during the observation period. It is generally accepted that best virological responses are seen in patients with treatment adherence rates above 90–95% suggesting thus that lower adherence may subsequently translate into an inferior virological outcome [40,43]. Few other randomized intervention trials to improve adherence to antiretroviral therapy have been conducted: Tuldra and colleagues randomized 116 patients to compare standard care with additional psychoeducative training. A total of 94% of the participants in the intervention group versus 69% in the control group had an adherence rate of more than 95% at week 48 [52]. Overall virological outcome did not differ between study groups, but adherence of >95% was associated with superior virological outcome. Pradier and colleagues randomized 244 patients to assess the impact of three individual educational and counselling interventions provided by trained nurses in addition to standard of care. Adherence was improved in the intervention group but virological outcome was similar in both study groups [44]. Unpublished data indicated improved adherence and virological outcome among patients randomized to additional counselling by hospital pharmacists versus standard care [35]. Supervised care of persons with tuberculosis [8] or HIV infection [33], daily observed therapy, or therapy in prisoners have resulted in superior outcome. Autonomous individuals, however, generally do not want to be dependent on permanent external control to attain their goals. Conceptual models on adherence to therapy have been developed proposing that the complex interaction of various factors associated with adherence must be considered in order to offer tailored therapy: variables include the characteristics of drugs and drug combinations, pill count, patient–physician interaction, patients’ knowledge on disease, his or her belief in value of therapy, stage of readiness and motivation for treatment, and patients’ skills to organize pill intake in daily living [45]. This process may be positively influenced by behavioural support [46]. Our 92
study adds proof of concept that behaviour cognitive intervention indeed can be indicated to help individuals to better accomplish adherence to antiretroviral therapy. In conclusion, maintenance of adherence to antiretroviral combination therapy was more stable over time among a group of patients to whom an individual cognitive behaviour intervention was offered in addition to standard of care. Future work needs to identify specific elements or steps in the intervention process that are predictive for success. It will be important to investigate whether short-term or time-limited intervention (in contrast to continuous long-term psychotherapeutic intervention) would also result in long-term benefit. Furthermore, it may be considered to use cognitive behaviour intervention before initiating antiretroviral treatment. Our study needs to be replicated among patients who newly start therapy. Improved tailored antiretroviral therapy considering particular needs of individual patients may be achieved by interdisciplinary collaboration of physicians and cognitive behavioural therapists.
Acknowledgements We are indebted to the participants and to the physicians of the HIV outpatient clinic at the University Hospital, Zurich, Switzerland, for patient care and data collection. We thank the psychotherapists (Urs Eichenberger, Barbara Heiniger Haldimann, René Bridler, Sonja Sterchi-Birzle, Claudia Baltensperger, Susanne Baumann, Nora Kaiser, Bettina Schindler Helmy, Robert Frei and Heinz-Peter Mueller) for study participation, patient care and data collection, and Bernard Limacher and Hansruedi Ambühl for supervision of the psychotherapists.
Members of the Swiss HIV Cohort Study group M Battegay, E Bernasconi, H Bucher, Ph Bürgisser, M Egger, P Erb, W Fierz, M Fischer, M Flepp (Chairman of the Clinical and Laboratory Committee), P Francioli (President of the SHCS, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland), HJ Furrer, M Gorgievski, H Günthard, P Grob, B Hirschel, L Kaiser, C Kind, Th Klimkait, B Ledergerber, U Lauper, M Opravil, F Paccaud, G Pantaleo, L Perrin, J-C Piffaretti, M Rickenbach (Head of Data Center), C Rudin (Chairman of the Mother & Child Substudy), J Schupbach, R Speck, A Telenti, A Trkola, P Vernazza (Chairman of the Scientific Board), Th Wagels, R Weber and S Yerly.
Sources of financial support This study was financed by the Swiss National Science Foundation (Grant no. 3345-61386). The electronic drug exposure monitoring system (eDEM) was ©2004 International Medical Press
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financed with an unrestricted grant of GlaxoSmithKline, Switzerland. The Swiss HIV Cohort Study is financed by the Swiss National Science Foundation (Grant no. 3345-062041). The psychotherapists were reimbursed for each session using grant money according to the regular tariff used in the Canton of Zurich, Switzerland, that is, 160.00 Swiss Francs per hour (114.00 US Dollars).
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Received 4 July 2003; accepted 9 October 2003
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Appendix Questionnaire on experience and behaviour (original German Version: Veränderungsfragebogen des Erlebens und Verhaltens) [55,58] Instructions Please think about the time directly prior to the study. Remember what you were doing at that time and how you felt. Then think of the period between then and now. For each of the following questions, please think about whether, within the period of time since the beginning of the study, you have experienced a change for the better or for the worse. Please indicate the extent of the change by marking the appropriate circle with a cross, like this: I now feel more settled (1) – (2) – (3) – (4) – (5) – (6) – (7) I now feel more unsettled If you did not experience any change during the period in question, that is to say if you are now feeling neither more nor less settled, you would mark the middle circle (4) with a cross. If you most definitely feel more settled, you should mark the first circle on the left (1); if you most definitely feel more unsettled, you should mark the circle furthest to the right (7). Please answer the questions spontaneously, intuitively, and according to what best corresponds to how you feel.
As compared to the time just prior to the study … 1 2 3
11 12
… there seems to be less going on in my life ... I am happier with myself ... I feel more relaxed when it comes to facing difficulties ... I feel more settled ... I have less stamina ... I give up more quickly ... I am in better spirits now … I feel more confident now ... I am now more relaxed when interacting with other people ... I feel less concerned when I think about the future ... I react more calmly to unexpected events … now I sometimes don’t know how to go on
13 14 15 16 17 18 19
... I now have less confidence in myself … my life makes more sense ... I feel more light-hearted ... I feel less equal to my tasks ... I am more relaxed ... I feel more even-tempered ... I have a clearer picture of myself and my future
20
... I somehow have a more optimistic view of things (1) – (2) – (3) – (4) – (5) – (6) – (7)
21
... I think I now have a better understanding of what is important for me ... I am now better able to come to terms with my problems ... I no longer feel so insecure when talking to other people ... I don’t feel so good about myself ... I am better able to cope with the difficulties of everyday life ... I am less afraid of failing at something I need to accomplish ... I am now experiencing greater self-acceptance
4 5 6 7 8 9 10
22 23 24 25 26 27
(1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7)
(1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7) (1) – (2) – (3) – (4) – (5) – (6) – (7)
… there seems to be more going on in my life ... I am less happy with myself ... I feel less relaxed when it comes to facing difficulties ... I feel more unsettled ... I have more stamina ... I don’t give up so soon ... I am more despondent … I feel less confident now ... I am now more tense when interacting with other people ... I feel more concerned when I think about the future ... I am more perturbed by unexpected events … now I often have a better feeling about how to go on ... I now have more confidence in myself … my life makes less sense ... I feel more troubled ... I feel more equal to my tasks ... I am more tense ... I feel less even-tempered ... I don’t have such a clear picture of myself and my future ... I somehow have a less optimistic view of things ... I think I now don’t have such a good understanding of what is important for me ... I am now less able to come to terms with my problems ... I feel more insecure when talking to other people ... I feel better about myself ... I am less able to cope with the difficulties of everyday life ... I am more afraid of failing at something I need to accomplish ... I am now experiencing lower self-acceptance
Thank you very much for your cooperation! Antiviral Therapy 9:1
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