Search

01 augustus 2023, Item does not contain fulltext, BACKGROUND: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyse the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate its effectiveness. METHODS: In this large-scale, national questionnaire study, questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorised as non-responder (≤50 BAU/mL), low-responder (>50 ≤ 300 BAU/mL) or high-responder (>300 BAU/mL), and shared with participants as a correlate of protection. Participants of whom demographics on sex and age, blood samples and completed questionnaires were available, were included. Our study took place between February 2021 and January 2022. The primary outcome of adherence before and after vaccination was assessed between August and October 2021 and compared via the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and non-adherence, and adherence on acquiring SARS-CoV-2 infection. This study is registered at ClinicalTrials.gov (NCT04841785). FINDINGS: In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after vaccination (4.56, IQR 4.11-4.78 and 4.22, IQR 3.67-4.67, p < 0.001). Adherence after awareness of antibody response was analysed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-r

Item does not contain fulltext, INTRODUCTION: Monitoring of adherence to antiretroviral treatment (ART) is of utmost importance to prevent treatment failure. Several measures to monitor adherence have been applied in low-resource settings and they all have pros and cons. Our objective was to examine whether any of the following adherence measures is a better predictor of participants' viral load suppression: (1) self-report, (2) pharmacy refill count, (3) Real Time Medication Monitoring (RTMM), (4) a combination of self-report and pharmacy refill count or (5) all three adherence assessment methods combined. METHODOLOGY: This was a post-hoc analysis of data from our 48-week REMIND-HIV randomized controlled trial in which adherence to ART was measured using self-report, pharmacy refill counts and RTMM among ART-experienced adults living with HIV subjectively judged to be nonadherent to ART. For each adherence measure, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting virological failure defined as a viral load (VL) of > 20 copies/mL. To determine at which percentage of adherence the prediction was strongest, we evaluated adherence cut-offs of 80%, 85%, 90%, 95% and 100% using receiver operating characteristic (ROC) curves. VL data were obtained after 48 weeks of follow-up in the trial. RESULTS: A total of 233 people living with HIV (PLHIV) were included in this analysis. When comparing the ability of self-reported adherence with pharmacy refill count and RTMM adherence to predict viral load > 20 copies/ml, self-reported adherence had the lowest sensitivity, ranging from 6 to 17%, but the highest specificity, ranging from 100 to 86%, depending on cut-off values from 80 to 100%. Area under the ROC curves (AUC) were 0.54 for RTMM, 0.56 for pharmacy refill count and 0.52 for self-report, indicating low discriminatory capacity for each of the adherence measures. When we combined the self-report and pharmacy refill count measures, se

Item does not contain fulltext

Contains fulltext : 232004.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Digital Adherence Tools (DAT) to promote adherence to antiretroviral treatment (ART) for HIV are being increasingly adopted globally, however their effectiveness and acceptability in limited resource settings has been challenging. In this study, we examine the acceptability of DATs to improve adherence to ART. METHODS: This study was part of a three-arm randomized controlled trial (REMIND) which investigated the effect of two different DAT's: SMS text messages (SMS) or real-time medication monitoring (RTMM) on treatment adherence; compared to standard of care. Exit interviews and in-depth interviews were conducted at 48 weeks follow-up, to collect data on their experiences (successes, challenges, and barriers) and behaviours regarding the implementation of the interventions. Translated transcripts, memos and field notes were imported to NVivo software version 12. We used a thematic framework analysis which drew from Sekhon's theoretical framework of acceptability (TFA), which comprises of seven constructs (affective attitude, perceived burden, perceived effectiveness, ethicality, self-efficacy, intervention coherence and opportunity costs). RESULTS: Of the 166 participants enrolled, 143 (86%) were interviewed (68 in the SMS arm and 75 in the RTMM arm). Participants were highly satisfied (98%) with the DAT system and the majority of them reported it motivated them to take their medication (99%). The majority of participants reported they were confident in their ability to comply with the intervention and understood how the intervention worked (97%). Very few reported negatively about the devices (carrying the device), with only 6% reporting that they did not feel comfortable and 8% had ethical concerns with the SMS-content A few participants reported challenges with their connectivity/network and that the visits were too time-consuming. A few participants reported that they incurred extra cost for the sake of the study. CONCLUSION: Overall, the acceptab

Item does not contain fulltext, BACKGROUND: Lifelong adherence to antiretroviral treatment remains challenging for people living with HIV (PLHIV). The aim of this study was to investigate whether any of 2 digital adherence tools could improve adherence among PLHIV in Kilimanjaro, Tanzania. METHODS: We performed a parallel 3-arm, nonblinded, randomized controlled trial with 1:1:1 allocation. We included adults aged between 18 and 65 years, living in Kilimanjaro region, and who were on antiretroviral treatment for at least 6 months. Their adherence, as judged by the study nurses, had to be suboptimal. In one arm, participants received reminder short message service (SMS) texts, followed by a question SMS. In the second arm, participants received a real-time medication monitoring (RTMM) device (Wisepill) with SMS reminders. In the third arm, participants received standard care only. The primary outcome of mean adherence over 48 weeks was compared between arms using between-group t tests in a modified intention-to-treat analysis. RESULTS: In each arm, we randomized 83 participants: data of 82 participants in the RTMM arm, 80 in the SMS arm, and 81 in the standard care arm were analyzed. The average (over 48 weeks) adherence in the SMS, RTMM, and control arms was 89.6%, 90.6%, and 87.9% for pharmacy refill; 95.9%, 95.0%, and 95.2% for self-report in the past week; and 97.5%, 96.6%, and 96.9% for self-report in the past month, respectively (P values not statistically significant). CONCLUSIONS: Receiving reminder SMS or RTMM combined with feedback about adherence levels and discussion of strategies to overcome barriers to adherence did not improve adherence to treatment and treatment outcome in PLHIV. CLINICAL TRIAL NUMBER: PACTR201712002844286.

Item does not contain fulltext

Contains fulltext : 220557.pdf (publisher's version ) (Open Access), BACKGROUND: Mobile communication has been found to improve antiretroviral therapy (ART) adherence among people living with HIV. In an ongoing randomized clinical trial, 2 mobile communication strategies (ie, sending SMS text messages and real-time medication monitoring [RTMM]) were used to improve adherence to ART among people living with HIV in Tanzania. We noticed remarkable discrepancies between self-reported adherence and adherence recorded by SMS text messaging or RTMM among some of the first trial participants. OBJECTIVE: Our objective was to describe these cases and the observed discrepancies in more detail, to serve as a useful illustration of some of the challenges in using mobile health in resource-limited settings. METHODS: In an ongoing randomized trial, adults living with HIV from two HIV treatment centers in Tanzania who were suspected of low levels of adherence were randomly assigned in a 1:1:1 ratio to receive (1) SMS text message reminders, (2) an RTMM device, or (3) no additional intervention to standard HIV care. During bimonthly study visits, the participants self-reported their level of adherence, received feedback about their level of adherence based on SMS text messaging or RTMM, and discussed strategies to overcome adherence problems with nurses providing HIV care. For the purpose of this report, we selected people living with HIV who had completed 5 follow-up visits and consistently reported more than 95% adherence, while SMS text messaging or RTMM recorded lower than 75% adherence. The participants were invited for a short, face-to-face in-depth interview to explore reasons for this discrepancy. RESULTS: At the time of this analysis, 26 participants had completed follow-up. Six of these evidenced the above-mentioned discrepancies, with an average adherence of 46% based on SMS text messaging or RTMM, while self-reported adherence was 98%. Five of these 6 participants insisted that their adherence to ART was good, with 4 reporting that their

Contains fulltext : 225347.pdf (publisher's version ) (Open Access), Real-time medication monitoring (RTMM) may potentially enhance adherence to antiretroviral treatment (ART). We describe a participant in an ongoing trial who, shortly after completing trial participation, died of cryptococcal meningitis despite high levels of adherence according to self-report, pill-counts and RTMM (> 99%). However, she evidenced consistently high HIV viral load throughout the 48-week study follow-up. Subsequently, her relatives unsolicitedly returned eight months' dispensed ART medication that she was supposed to have taken. This brief report illustrates the challenges of adherence measurements including RTMM, and reinforces the need to combine adherence assessments with viral load monitoring in HIV care.

Contains fulltext : 214470.pdf (publisher's version ) (Closed access)

Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients’ response of less than “all-of the time” to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of <95% medication possession ratio (MPR). Logistic regression models were fitted to identify factors associated with sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count.

HIV-infected migrants were shown to have poorer treatment outcomes than Dutch HIV-infected patients, often due to worse treatment adherence. Self-reported adherence would be an easy way to monitor adherence, but its validity relative to pharmacy refill adherence has not been extensively evaluated in migrants. All HIV-infected migrants older than 18 years and in care at the two Rotterdam HIV-treatment centers were eligible. Refill data with leftover medication (PRL) (residual pill count) were obtained from their pharmacies up to 15 months prior to inclusion. Self-reported adherence to combination Antiretroviral Therapy was assessed by four questions about adherence at inclusion. Additionally, risk factors for pharmacy refill non-adherence were examined. In total, 299 HIV-infected migrants were included. Viral load (VL) was detectable in 11% of the patients. Specificity of PRL was 53% for patients with an adherence of 100% and decreased with lower cut-off values. Sensitivity and negative predictive value (NPV) were 68% and 15% and increased with lower cut-off values. Positive predictive value (PPV) was around 93% for all cut-off values. Using the self-reported questions, 139 patients (47%) reported to be adherent. Sensitivity was 49% and specificity was 72%. PPV and NPV were 95% and 13%. No risk factors for pharmacy refill non-adherence were found in multivariable analyses. Both PRL and self-reported adherence, can predict undetectable VL in HIV-infected migrants. PPV and NPV are similar for both methods. This study shows that using four self-reported items is sufficient to predict adherence which is crucial for optimal clinical outcome in HIV-infected migrants.

Contains fulltext : 172552.pdf (publisher's version ) (Closed access), HIV infected and tuberculosis (TB) patients need high levels of treatment adherence to achieve optimal treatment outcomes. We conducted a pilot-study on real time medication monitoring (RTMM) in a resource-limited setting. We enrolled five HIV infected and five TB patients from Kilimanjaro, Tanzania. They took their medication using RTMM. When the device was not opened on time, patients received a reminder SMS. After 3 months, we interviewed patients. Six patients (60 %) reached adherence of >95 %. Nine-hundred-twenty-two of 1104 intakes (84 %) were on time. Five-hundred reminders (45 %) were sent, of which 202 (40 %) were incorrect, because of an unstable mobile network. Nine patients found the device helpful and nine mentioned it keeps medication safe. Six patients reported that the size was too big. Five patients mentioned they received incorrect reminders. The device is considered useful in Kilimanjaro. Optimization of the device should consider network connectivity and the size of the device.

In the Netherlands, immigrant people living with HIV (PLWH) have poorer psychological and treatment outcomes than Dutch PLWH. This cross-sectional field study examined risk factors for non-adherence to combination Antiretroviral Therapy (cART) among immigrant PLWH. First and second generation immigrant PLWH attending outpatient clinics at two HIV-treatment centers in Rotterdam were selected for this study. Socio-demographic and clinical characteristics for all eligible participants were collected from an existing database. Trained interviewers subsequently completed questionnaires together with consenting participants (n = 352) to gather additional data on socio-demographic characteristics, psychosocial variables, and self-reported adherence to cART. Univariable and multivariable logistic regression analyses were conducted among 301 participants who had used cART 6 months prior to inclusion. Independent risk factors for self-reported non-adherence were (I) not having attended formal education or only primary school (OR = 3.25; 95%CI: 1.28-8.26, versus University), (II) experiencing low levels of social support (OR = 2.56; 95%CI: 1.37-4.82), and (III) reporting low treatment adherence self-efficacy (OR = 2.99; 95%CI: 1.59-5.64). Additionally, HIV-RNA >50 copies/ml and internalized HIV-related stigma were marginally associated (P<0.10) with non-adherence (OR = 2.53; 95%CI: 0.91-7.06 and OR = 1.82; 95%CI: 0.97-3.43). The findings that low educational attainment, lack of social support, and low treatment adherence self-efficacy are associated with non-adherence point to the need for tailored supportive interventions. Establishing contact with peer immigrant PLWH who serve as role models might be a successful intervention for this specific population.

Contains fulltext : 153779.pdf (publisher's version ) (Open Access), BACKGROUND: In patients with a space-occupying middle cerebral artery (MCA) infarct surgical decompression reduces the risk of death, but increases the chance of survival with severe disability. We assessed quality of life (QoL), symptoms of depression, and caregiver burden at long-term follow-up. METHODS: Patients treated in two academic centres between 2007 and 2012 were included. Follow-up was at least six months. Patients and caregivers were interviewed separately. QoL was assessed with a visual analogue scale and the 36-item Short-Form health survey (SF-36); depression with the Hospital Anxiety and Depression Scale; and caregiver burden with the Caregiver Strain Index. RESULTS: Twenty five patients were enrolled, of whom seven had an infarct in the dominant hemisphere. After a median follow-up of 26 months (IQR 11-46) the median SF-36 mental component score was 54.4 (IQR 45-60), indicating a mental QoL comparable to that in the general population. The median SF-36 physical component score was 32.7 (IQR 22-38), indicating a worse physical QoL. Dominance of the hemisphere did not influence QoL. 79 % of patients and 65 % of caregivers would, in retrospect, again choose for surgery. 26 % of patients had signs of depression and 64 % of caregivers were substantially burdened in their daily life. CONCLUSIONS: Mental QoL after surgical decompression for space-occupying MCA infarct is comparable to that in the general population, whereas physical QoL is worse. Dominance of the hemisphere did not influence QoL. The majority of caregivers experience substantial burden. Most patients and caregivers stand by their decision for hemicraniectomy.

Background: Patient retention in chronic HIV care is a major challenge following the rapid expansion of combination antiretroviral therapy (cART) in Ethiopia. Objective: To describe the proportion of patients who are retained in HIV care and characterize predictors of attrition among HIV-infected adults receiving cART in Addis Ababa. Method: A retrospective analysis was conducted among 836 treatment naïve patients, who started cART between May 2009 and April 2012. Patients were randomly selected from ten healthcare facilities, and their current status in HIV care was determined based on routinely available data in the medical records. Patients lost to follow-up (LTFU) were traced by telephone. Kaplan-Meier technique was used to estimate survival probabilities of retention and Cox proportional hazards regression was performed to identify the predictors of attrition. Results: Based on individual patient data from the medical records, nearly 80% (95%CI: 76.7, 82.1) of the patients were retained in care in the first 3 and half years of antiretroviral therapy. After successfully tracing more than half of the LTFU patients, the updated one year retention in care estimate became 86% (95% CI: 83.41%, 88.17%). In the multivariate Cox regression analyses, severe immune deficiency at enrolment in care/or at cART initiation and 'bed-ridden' or 'ambulatory' functional status at the start of cART predicted attrition. Conclusion: Retention in HIV care in Addis Ababa is comparable with or even better than previous findings from other resource-limited as well as EU/USA settings. However, measures to detect and enroll patients in HIV care as early as possible are still necessary.

Contains fulltext : 79834.pdf (publisher's version ) (Closed access), In industrialized countries, virological failure occurs more often among HIV-infected immigrant patients. Non-adherence is the most credible explanation. We compared adherence of immigrant patients with that of non-immigrant patients in the Netherlands, and investigated which method of adherence measurement is most suitable for daily use to predict virological treatment failure: testing knowledge of the current regimen, a quantitative adherence interview, pharmacy prescription refill ratio (dispensed medication divided by prescribed medication, DM/PM), and plasma drug levels. Included were 61 immigrants and 81 non-immigrants. Virological failure did occur more often in immigrants than in non-immigrants (19.7% (12/61) versus 8.6% (7/81), p=0.056), especially among previously naive patients (19.6% (11/56) versus 0% (0/54), p<0.01). There were no differences between both groups on any of the four adherence measures. Virological failure was associated with reporting stopping medication when not feeling well (OR=12, 95%CI=1.9-77.7, p=0.02), and, among naive patients, also with a DM/PM < 0.85 (Odds Ratio=5.1, 95%Confidence Interval=1.2-22.3, p=0.03). Although our study confirmed a much higher virological failure rate among immigrants, we were unable to identify clear differences in adherence between immigrants and non-immigrant patient, although virological failure was associated with stopping medication when not feeling well and a low DM/PM. Unstructured treatment interruptions are a likely explanation of the findings. Interventions should be aimed at preventing patients to stop medication. A DM/PM below 0.85 can be indicative for patients who did stop medication and are at risk for virological failure.

Contains fulltext : 80845.pdf (publisher's version ) (Closed access), Pulmonary arterial hypertension associated with congenital heart disease caused by systemic-to-pulmonary shunting was associated with a high risk of morbidity and mortality. In this retrospective study, the longer term treatment effect of bosentan on exercise capacity and quality of life (QoL) were evaluated in 58 adult patients (>18 years) with pulmonary arterial hypertension associated with congenital heart disease, including patients with Down's syndrome. All patients were evaluated at baseline and during follow-up using laboratory tests, 6-minute walk test, QoL questionnaires, and Doppler echocardiography. Treatment efficacy was analyzed separately for patients without (n = 30) and with Down's syndrome (n = 28). Median follow-up of all patients treated with bosentan was 22 months (range 3 to 36). In patients without Down's syndrome, mean 6-minute walk distance increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment, followed by a gradual return to baseline and disease stabilization. QoL improved significantly during treatment and was maintained during 18 months of follow-up (p <0.05). In patients with Down's syndrome, 6-minute walk distance and QoL were stable during treatment. In conclusion, findings suggested that in patients without Down's syndrome, longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity.

Contains fulltext : 71206.pdf (publisher's version ) (Closed access), Exercise is recommended in patients with left ventricular failure. Although right ventricular failure is common in patients with a systemic right ventricle (RV), no data are available on the effect of physical activity in these patients. The aim of this study was to evaluate the relation of physical activity and cardiac function, exercise capacity, and quality of life in patients with a systemic RV. Forty-seven patients (64% men, mean age 35 years, range 21 to 69) with a systemic RV (31 with an atrially switched transposition of the great arteries and 16 with a congenitally corrected transposition of the great arteries) were included. Cardiac function was assessed by cardiovascular magnetic resonance or computed tomography, exercise tests, and serum N-terminal prohormone brain natriuretic peptide (NT-pro-BNP) levels. Habitual physical activity was assessed using the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH) and quality of life using the Medical Outcomes Study Short Form 36-Item Health Survey. Mean systemic right ventricular ejection fraction was impaired (36.8 +/- 7.8%), as was maximal exercise capacity (78.5 +/- 23.9% of predicted). NT-pro-BNP level was increased (median 269 ng/L, range 34 to 4,476). Mean SQUASH score was 6,808 +/- 3,241, indicating a decreased level of habitual physical activity. Although patients' scores on mental quality-of-life domains were comparable to the general population, scores on most physical quality-of-life domains were significantly lower. SQUASH scores were found to be a significant predictor for exercise capacity (p <0.01) and physical quality of life (p <0.001). However, we found no relation between SQUASH scores and right ventricular ejection fraction or NT-pro-BNP. In conclusion, physical activity in patients with a systemic RV is positively associated with exercise capacity and quality of life, irrespective of cardiac performance.

Contains fulltext : 178670.pdf (publisher's version ) (Closed access), Background: Adaptation to changing health presents a challenge to measuring change in quality of life (QoL). Previous studies have shown that different methods for measuring change yield different results, but it is unclear which method provides a more valid measurement of change. We investigated which of 3 commonly used methods for measuring change in QoL yielded the strongest associations with clinical measures of change in health status. Methods: A total of 268 human immunodeficiency virus (HIV)-1-infected patients starting highly active antiretroviral therapy completed QoL measures at baseline and after 36 weeks. We calculated Pearson correlation coefficients between change in QoL according to a prospective baseline and prospective follow-up measurement, a retrospective baseline and prospective follow-up measurement, or retrospective transition questions and change in CD4-cell count, plasma viral-load, body mass index, and hemoglobin concentration. Results: Patients evaluated their QoL significantly worse on the retrospective than on the prospective baseline measurement (P < 0.01). These results may indicate that patients' reference value by which they evaluate their QoL changed over time, which would invalidate prospective serial QoL measurements. The retrospective baseline measurement method yielded strongest associations with clinical measures of change (P = 0.02 to P < 0.01). Distinguishing between the change inferred from the conventional prospective and the retrospective baseline measurement method was meaningful because the prospective method did not lead to changes that would be considered clinically significant, whereas the retrospective baseline measurement method did. Conclusions: A method for measuring change in QoL incorporating a retrospective baseline-measurement showed strongest associations with change in clinical indicators of health status, suggesting a more valid measurement of change in QoL than a conventional prospective method.

Contains fulltext : 119497.pdf (publisher's version ) (Closed access), The relationship between plasma concentrations of nelfinavir and virologic treatment failure was investigated to determine the minimum effective concentration of nelfinavir. Plasma samples were prospectively collected from treatment-naive patients who began taking nelfinavir, 1,250 mg BID + two nucleoside reverse transcription inhibitors (NRTIs). Nelfinavir concentration ratios were calculated by dividing each individual nelfinavir level by the time-adjusted population value. Virologic failure was defined as either no response (a detectable viral load after 6 months) or a relapse (detectable viral load after being undetectable, or an increase in viral load >1 log above nadir). Forty-eight patients were included with a median follow-up period of 8 months. The median concentration ratio of nelfinavir was 0.98 (interquartile range, 0.76-1.47). Virologic failure was observed in 29% of the patients. In a univariate analysis, the nelfinavir concentration ratio appeared to be the single determinant that was related to virologic failure (P = 0.039). Patients with a median ratio <0.90 had a relative risk of 3.0 (95% CI, 1.2-7.6) for virologic failure. Using this threshold, virologic failures were detected with 64% sensitivity and 74% specificity (P = 0.014). Virologic failure of nelfinavir-containing triple therapy can be explained, to a large extent, by low plasma levels of nelfinavir.

Contains fulltext : 119508.pdf (publisher's version ) (Closed access), OBJECTIVE: To determine plasma concentration ratio limits (CORALS) for HIV-protease inhibitors outside of which random plasma concentrations reflect partial compliance or noncompliance. In the absence of a gold standard for measuring compliance and to avoid complex techniques, measuring plasma concentrations may be an objective and easy way to check noncompliance. METHODS: Pharmacokinetic curves after observed ingestion were recorded in patients on steady-state indinavir 800 mg TID (n = 22), ritonavir 400 mg/saquinavir 400 mg BID (n = 22, ritonavir; n = 17, saquinavir hard-gel capsules), or nelfinavir 750 mg TID (n = 4) or 1250 mg BID (n = 4). Concentration ratios were calculated by dividing the measured concentration by the median population value at the corresponding sampling time. Limits were based on the minimum P(05) (5th percentile) and maximum P(95) of these ratios found during the sampling interval. With these limits the authors determined (1) the proportion of patients falsely judged as noncompliers after observed ingestion, (2) discrimination between compliers and noncompliers, and (3) the absolute percentage of noncompliers. To judge the last two elements, two sets of random plasma samples were included: (1) samples sent in by the physician on suspicion of noncompliance (indinavir, n = 42; nelfinavir, n = 22;) or from a study population stating imperfect compliance in a questionnaire (ritonavir/saquinavir, n = 11); (2) control samples sent in routinely for monitoring therapeutic levels (indinavir, n = 41; nelfinavir, n = 201) or drawn from patients who stated perfect compliance in the questionnaire (ritonavir/saquinavir, n = 35). RESULTS: The following CORALS were found: indinavir <0.23 or >3.3; nelfinavir <0.36 or >2.1; ritonavir <0.18 or >1.9; saquinavir <0.28 or >2.3. In 31% to 55% of the patients suspected of noncompliance a plasma concentration ratio outside these limits was found. If a ratio was outside the limits, there was a 68% to 88% chance that

Contains fulltext : 185695.pdf (publisher's version ) (Closed access), BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) for human immunodeficiency syndrome type 1 (HIV-1) infection is essential to sustain viral suppression and prevent drug resistance. We investigated adherence to HAART among patients in a clinical cohort study. METHODS: Patients receiving HAART had their plasma concentrations of protease inhibitors or nevirapine measured and completed a questionnaire on adherence. We determined the percentage of patients who reported taking all antiretroviral medication on time and according to dietary instructions in the past week. Drug exposure was compared between patients reporting deviation from their regimen and fully adherent patients. Among patients who received HAART for at least 24 weeks, we assessed the association between adherence and virologic outcome. RESULTS: A total of 224 of 261 eligible patients completed a questionnaire. Forty-seven percent reported taking all antiretroviral medication on time and according to dietary instructions. Patients who reported deviation from their regimen showed lower drug exposure compared with fully adherent patients (median concentration ratio, 0.81 vs 1.07; P =.001). Among those receiving HAART for at least 24 weeks, patients reporting deviation from their regimen were less likely to have plasma HIV-1 RNA levels below 500 copies/mL (adjusted odds ratio, 4.0; 95% confidence interval, 1.4-11.6) compared with fully adherent patients. CONCLUSIONS: Only half of the patients took all antiretroviral medication in accordance with time and dietary instructions in the preceding week. Deviation from the antiretroviral regimen was associated with decreased drug exposure and a decreased likelihood of having suppressed plasma HIV-1 RNA loads. Patient adherence should remain a prime concern in the management of HIV-1 infection.