Search PubMed⌕ Search

Biomedical subjects

Jeanne P Dieleman

Publications and source records attributed to Jeanne P Dieleman.

At least 19 recordsLinked to original sources
PubMed2006

Annual influenza vaccination in community-dwelling elderly individuals and the risk of lower respiratory tract infections or pneumonia.

BACKGROUND: Influenza vaccination has been associated with a reduction in the number of hospitalizations for respiratory conditions in elderly persons over the period from 1996 to 2002. Little is known, however, about the effect of influenza vaccination on the whole range of severity of respiratory tract infections. METHODS: We investigated the effect of annual influenza vaccination on the occurrence of lower respiratory tract infections (LRTIs) in community-dwelling elderly individuals. From 1996 to 2002, we performed a population-based cohort study, using the computerized Integrated Primary Care Information database in the Netherlands, of community-dwelling subjects who were 65 years or older on January 1 of the year of study entry. For each year, the individual cumulative exposure to influenza vaccination since study entry was computed. We compared the risk of LRTI after a first vaccination or revaccination with the risk for no vaccination using a time-varying multivariate Cox proportional hazard model, adjusted for age, sex, smoking, and underlying disease. RESULTS: In the study population of 26 071 subjects, 3412 developed LRTIs during follow-up. During the influenza epidemic periods, a first vaccination did not reduce risk for LRTI. In the total population, the hazard ratio following a first vaccination was 0.86 (95% confidence interval [CI], 0.71 to 1.05); in the population without or with comorbidity, these ratios were 0.90 (95% CI, 0.56 to 1.45) and 0.83 (95% CI, 0.66 to 1.04), respectively. During epidemic periods, revaccination reduced risk of LRTI by 33% (95% CI, 8% to 52%) in individuals without comorbidity. In individuals with comorbidity, the risk reduction of 5% was nonsignificant (95% CI, -10% to 18%). CONCLUSION: In this study, annual influenza revaccination was associated with a reduction in LRTI in community-dwelling elderly individuals.

Age Factors↗
PubMed2006

Channeling and prevalence of cardiovascular contraindications in users of cyclooxygenase 2 selective nonsteroidal antiinflammatory drugs.

OBJECTIVE: To assess use and channeling of cyclooxygenase 2 selective inhibitors (coxibs) over time and to estimate the percentage of coxib users with cardiovascular contraindications. METHODS: The study population comprised all coxib and nonselective nonsteroidal antiinflammatory drug (NSAID) users in the Integrated Primary Care Information project between January 2000 and December 2004. The prevalence of risk factors for NSAID-related upper gastrointestinal ulcer complications, cardiovascular disease, and cerebrovascular disease at the start of treatment was compared between users of coxibs and users of nonselective NSAIDs. RESULTS: The study population included 72,841 nonselective NSAID users and 10,739 coxib users. The prevalence of risk factors for NSAID-related gastrointestinal complications was higher in coxib users than nonselective NSAID users (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.10-1.26). Similarly, the prevalence of prior cardiovascular disease was higher in coxib users than in nonselective NSAID users (OR 1.35, 95% CI 1.28-1.43). Channeling of coxibs to patients with NSAID-related gastrointestinal risk factors declined after 2001 but increased again in 2004, whereas the channeling of coxibs to patients with cardiovascular disease remained constant. Less than 15% of all coxib users had history of ischemic coronary or cerebrovascular disease. Among coxib users with increased risk for NSAID-related gastrointestinal disorders, 27% had history of ischemic coronary or cerebrovascular disease. CONCLUSION: This study demonstrates that coxibs were preferentially prescribed to patients with risk factors for NSAID-related gastrointestinal disorders and/or cardiovascular diseases. Only one-quarter of coxib users with increased risk for NSAID-related gastrointestinal complications had cardiovascular conditions compatible with recent European safety contraindications for coxibs.

Adolescent↗
PubMed2006

A randomized database study in general practice yielded quality data but patient recruitment in routine consultation was not practical.

OBJECTIVE: To assess patient recruitment and quality of data in a randomized database study. STUDY DESIGN AND SETTING: A randomized database study was conducted in the Integrated Primary Care Information (IPCI) general practice research database. Software was built to allow for automated patient identification and recruitment, and randomization. As an application, we compared gastrointestinal tolerability in persons treated with diclofenac and celecoxib for osteoarthritis. The outcomes were assessed in the IPCI database. To assess accuracy of exposure and outcome, we also collected information by self-administrated patient questionnaires. For all eligible subjects, we assessed the main reason for noninclusion. Physicians were interviewed to evaluate the study and to identify the major obstacles. RESULTS: Forty-two general practice physicians collaborated with the study and 7,127 potential study subjects were identified. Among these subjects, 170 were eligible for recruitment and 20 (11.8%) were randomized. Of the eligible patients, 96 (56.5%) were not recruited because the physician was too busy or the patient was treated by another healthcare provider and 54 (31.8%) were not recruited because of exclusion criteria. CONCLUSION: Concordance between questionnaires and IPCI data and the outcome was good (kappa=0.7; SD=0.14). The physicians reported that recruitment during routine visits was too time-consuming, in particular because of the need for informed consent. Although a randomized database study is feasible, patient recruitment during routine consultations should be avoided.

Adult↗
PubMed2005

A technical infrastructure to conduct randomized database studies facilitated by a general practice research database.

General practice research databases are increasingly used to study intended and unintended effects of treatments. However, confounding by indication remains a major problem. The randomized database study methodology has been proposed as a method to combine the strengths of observational database (generalizability) and the strength of the randomized clinical trial (RCT) design (randomization). We developed an infrastructure that enables the execution of randomized database studies with treatment randomization facilitated by a general practice research database. The requirements posed by the methodology of randomized database studies were facilitated by software components. Our assessment showed that it is technically possible to conduct randomized trials in general practice according to the randomized database design. The infrastructure facilitated the conduct of randomized database studies in general practice but some practical difficulties and methodological issues remain. The technical infrastructure seems to be both promising and potentially feasible to facilitate future randomized database studies, although the methodology needs to be evaluated in more detail.

Biomedical Research↗
PubMed2005

Nonsteroidal anti-inflammatory drugs and increased risk of acute urinary retention.

BACKGROUND: Acute urinary retention (AUR) is characterized by the sudden inability to urinate, which is usually extremely painful and requires catheterization. Prostaglandins play an important role in the genitourinary function as they provoke contractions of the detrusor muscle. Relaxation of the detrusor muscle, via the inhibition of the prostaglandin synthesis, could result in AUR. METHODS: We conducted a population-based case-control study within the Integrated Primary Care Information project in the Netherlands to investigate whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of AUR. All men 45 years or older registered in the database between 1995 and 2002 and with at least 6 months of valid history were included. Cases were all men with a validated diagnosis of AUR. To each case, up to 10 controls were matched on age and calendar time. RESULTS: Within the source population of 72 114 men, we identified 536 cases of AUR and 5348 matched controls. Risk of AUR was 2.02-fold higher in current users of NSAIDs than in nonusers (95% confidence interval, 1.23-3.31). The highest risk for AUR (adjusted odds ratio, 3.3; 95% confidence interval, 1.2-9.2) was observed in patients who recently started using NSAIDs and in those using a dose equal to or higher than the recommended daily dose. CONCLUSION: This study shows that the risk of AUR is about 2-fold higher in men who use NSAIDs.

Acute Disease↗
PubMed2005

Non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death.

AIMS: To assess the association between the use of non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death. METHODS AND RESULTS: A population-based case-control study was performed in the Integrated Primary Care Information (IPCI) project, a longitudinal observational database with complete medical records from more than 500,000 persons. All deaths between 1 January 1995 and 1 September 2003 were reviewed. Sudden cardiac death was classified based on the time between onset of cardiovascular symptoms and death. For each case, up to 10 random controls were matched for age, gender, date of sudden death, and general practice. The exposure of interest was the use of non-cardiac QTc-prolonging drugs. Exposure at the index date was categorized into three mutually exclusive groups of current use, past use, and non-use. The study population comprised 775 cases of sudden cardiac death and 6297 matched controls. Current use of any non-cardiac QTc-prolonging drug was associated with a significantly increased risk of sudden cardiac death (adjusted OR: 2.7; 95% CI: 1.6-4.7). The risk of death was highest in women and in recent starters. CONCLUSION: The use of non-cardiac QTc-prolonging drugs in a general population is associated with an increased risk of sudden cardiac death.

Adult↗
PubMed2005

Inappropriate drug prescribing in older adults: the updated 2002 Beers criteria--a population-based cohort study.

BACKGROUND: In 1997, Beers and colleagues developed explicit criteria for potentially inappropriate drug prescribing in ambulatory older adults aged 65 years and over. Several studies have been performed to estimate the prevalence of inappropriate drug prescribing based on these criteria. In 2002, the criteria were updated. AIMS: To examine the extent and trend of inappropriate drug prescribing to ambulatory older adults in the Netherlands between 1997 and 2001, according to the 1997 and the updated Beers criteria. METHODS: Data were retrieved from the Integrated Primary Care Information (IPCI) project, a general practice research database with data from computer-based patient records of a group of 150 general practitioners in the Netherlands. All subjects aged 65 and over were included. Prescriptions were classified as inappropriate if they fulfilled the Beers criteria of prescriptions that generally should be avoided in older adults because of a high risk of adverse effects, while also considering dose and comorbidity. RESULTS: Between 1997 and 2001, the 1-year risk of receiving at least one inappropriate drug prescription for older adults ranged between 16.8% (95% CI: 16.3-17.3%) and 18.5% (18.3-18.7%) according to the 1997 criteria and between 19.1% (18.6-19.6%) and 20.0% (19.5-20.5%) according to the updated Beers criteria. According to the updated criteria, the most frequently prescribed inappropriate drugs were nitrofurantoin, long-acting benzodiazepines, amitriptyline, promethazine and cimetidine. Temazepam and zolpidem were mostly prescribed in supratherapeutic dose. Conventional NSAIDs in persons with a history of gastric/duodenal ulcer were the most frequently prescribed contra-indicated drugs. CONCLUSIONS: Prescribing potentially inappropriate prescriptions to ambulatory older people in the Netherlands is substantial. Compared with other studies using the 1997 Beers criteria, inappropriate prescribing to the elderly is lower than in the USA but similar to Finland. Despite a restrictive medication policy and a growing attention for medication surveillance in Europe, inappropriate drug prescribing is still a substantial problem.

Aged↗
PubMed2005

Management of hypertension and hypercholesterolaemia in primary care in The Netherlands.

OBJECTIVE: Screening, treatment and monitoring guidelines for hypertension and hypercholesterolaemia have been developed to assist physicians in providing evidence-based health care. We conducted a retrospective study to assess the management of patients with these single or combined conditions. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study conducted using data from the Integrated Primary Care Information (IPCI) project based in The Netherlands. Management of hypertension and hypercholesterolaemia was assessed from 2000-2003 by measuring the numbers of patients screened for these conditions, treated pharmacologically and monitored for treatment success. RESULTS: Approximately 11%, 3% and 10% of participants were eligible for screening for hypertension alone, hypercholesterolaemia alone and both conditions, respectively. Blood pressure screening was high in patients eligible for both blood pressure and cholesterol screening (> 86%), whereas cholesterol screening was low (< 56%). Among patients newly identified with hypertension or hypercholesterolaemia who were eligible for pharmacotherapy, 29% and 43% respectively were not treated within one year of diagnosis. Undertreatment was significantly lower in patients with both conditions (24% and 37% for antihypertensive and lipid-lowering treatment, respectively and 28% were not treated for both). Among newly treated patients, in the first year of treatment there was no record of a blood pressure or cholesterol assessment, for 35% and 72%, respectively. CONCLUSION: Management was sub-optimal in patients with hypertension or hypercholesterolaemia as well as in those with both of these conditions. The results of this study are likely to be widely applicable, particularly to other European and industrialised countries that have similar free-access health care systems to The Netherlands.

Adolescent↗
PubMed2005

Differences between statins on clinical endpoints: a population-based cohort study.

OBJECTIVE: Many studies have shown differences between statins based on surrogate endpoints, but few have studied differences in reaching clinical endpoints. This study compares the risk of cardiovascular and cerebrovascular events between atorvastatin users and other statin users in daily general practice. RESEARCH DESIGN AND METHODS: A cohort study was performed in the Integrated Primary Care Information project database, a longitudinal general practice research database with electronic patient records of more than 500,000 individuals in The Netherlands. All new statin users in the period 1st September 1999 to 31st December 2002 were included. Multivariate Cox-regression analysis was used to compare the occurrence of the primary endpoint between atorvastatin users and other statin users. MAIN OUTCOME MEASURES: The primary endpoint was the composite outcome of fatal or non-fatal myocardial infarction, admission for unstable angina pectoris, fatal or non-fatal cerebrovascular accidents, or transient ischaemic events. RESULTS: 3499 new statin users were identified, including 797 patients with a history of cardiovascular disease. 1341 persons started with simvastatin (38.3%), 1154 with atorvastatin (33.0%), 811 with pravastatin (23.2%) and 193 with other statins (5.5%). The median follow-up was 1.9 years. Two hundred and thirty three patients (6.7%) experienced a primary endpoint. Atorvastatin users had a significantly lower risk of cardiovascular and cerebrovascular events than users of other statins (relative risk [RR]: 0.70, 95% confidence interval [CI]: 0.55-0.96). The relative risks of atorvastatin users compared to simvastatin and pravastatin users individually were 0.70 (95% CI: 0.48-1.02) and 0.78 (95% CI: 0.52-1.16), respectively. The protective effect of atorvastatin was more pronounced in persons without a history of cardiovascular or cerebrovascular events. CONCLUSION: Atorvastatin showed a more favourable effect on fatal and non-fatal cardiovascular and cerebrovascular events in the general population than other statins.

Adult↗
PubMed2004

Antibiotic prescribing for respiratory tract infections in Dutch primary care in relation to patient age and clinical entities.

OBJECTIVES: To obtain detailed information on current prescribing rates of antibiotics for respiratory tract infections (RTIs) in Dutch general practice and its relation with age and respiratory tract clinical entities. METHODS: We assessed the mean proportion of antibiotics prescribed for RTIs per age group, contact-based and population-based using all patient contacts concerning RTIs in the year 2000 selected from the IPCI database, containing information on general practice consultations of 235,290 patients. RESULTS: In one-third of all contacts concerning RTIs, antibiotics were prescribed, with much variation between age groups and clinical entities. For children (0-15 years) and the elderly (over 75 years), the lowest contact-based percentages of prescribed antibiotics for RTIs were found, while population-based, children of age 0-5 years received far more antibiotics for RTIs. High prescribing rates were seen in patients with sinusitis-like complaints (67%) or pneumonia (78%), whereas low rates were found for patients with upper RTIs (16%). CONCLUSIONS: Potential over-prescribing of antibiotics for RTIs occurs in the age group 31-65 years, not in children and the elderly, and in patients with upper RTIs, sinusitis and most likely acute bronchitis (contact-based). The management of these subgroups of patients should be addressed in quality assurance programmes. Children and the elderly visit the GP much more often than adults, which can be explained by more frequent (children) or more severe (elderly) RTI morbidity, but in proportion they do not receive more antibiotics.

Adolescent↗
PubMed2004

Antipsychotics and the risk of sudden cardiac death.

BACKGROUND: Antipsychotics have been associated with prolongation of the corrected QT interval and sudden cardiac death. Only a few epidemiological studies have investigated this association. We performed a case-control study to investigate the association between use of antipsychotics and sudden cardiac death in a well-defined community-dwelling population. METHODS: We performed a population-based case-control study in the Integrated Primary Care Information (IPCI) project, a longitudinal observational database with complete medical records from 150 general practitioners. All instances of death between January 1, 1995, and April 1, 2001, were reviewed. Sudden cardiac death was classified based on time between onset of cardiovascular symptoms and death. For each case, up to 10 random controls were matched for age, sex, date of sudden death, and practice. Exposure at the index date was categorized as 3 mutually exclusive groups of current use, past use, and nonuse. RESULTS: The study population comprised 554 cases of sudden cardiac death. Current use of antipsychotics was associated with a 3-fold increase in risk of sudden cardiac death. The risk of sudden cardiac death was highest among those using butyrophenone antipsychotics, those with a defined daily dose equivalent of more than 0.5 and short-term (</=90 days) users. The association with current antipsychotic use was higher for witnessed cases (n = 334) than for unwitnessed cases. CONCLUSIONS: Current use of antipsychotics in a general population is associated with an increased risk of sudden cardiac death, even at a low dose and for indications other than schizophrenia. Risk of sudden cardiac death was highest among recent users but remained elevated during long-term use.

Adolescent↗
PubMed2003

Persistent leukocyturia and loss of renal function in a prospectively monitored cohort of HIV-infected patients treated with indinavir.

Symptomatic nephrotoxicity is a well-known complication of indinavir treatment. However, little is known about the relevance of other abnormalities, such as leukocyturia during use of indinavir. We determined the prevalence, risk factors, and consequences of persistent leukocyturia in a prospectively monitored cohort of indinavir users in three adult outpatient clinics. Patients were monitored for nephrotoxicity at regular visits (every 3 months) between August 1998 and September 2000. Monitoring involved urine dipstick analysis and microscopy for pH, erythrocytes, leukocytes, and indinavir crystals. The urine albumin concentration/creatinine concentration ratio and serum creatinine and indinavir plasma concentrations were measured, and urinary tract infection was excluded. Urologic symptoms were retrieved from medical records. Of 184 patients with at least one assessment, 35% had leukocyturia (i.e., >75 cells/microL) at least once during the study period, which coincided with mild increase in the serum albumin level, erythrocyturia, and crystalluria. Thirty-two (24%) of 134 patients with two or more assessments had persistent leukocyturia (i.e., on two or more occasions). Risk factors were indinavir plasma concentration of >9 mg/L, urine pH of >5.7, and crystalluria. Persistent leukocyturia was associated with a gradual loss of renal function but not with urologic symptoms. The data show that leukocyturia is a frequent finding and emphasize the need for monitoring renal function during indinavir treatment, even in the absence of urologic symptoms.

Adult↗
PubMed2003

Low nevirapine plasma concentrations predict virological failure in an unselected HIV-1-infected population.

OBJECTIVE: To assess the relationship between plasma nevirapine concentrations and plasma HIV-1 RNA response in HIV-1-infected patients. DESIGN: An observational cohort analysis. METHODS: Plasma samples were obtained on a routine basis from 189 patients receiving nevirapine 200mg twice daily, and plasma nevirapine concentrations were measured with reversed phase high performance liquid chromatography. Patients were divided into two groups based on plasma nevirapine concentrations below (and equal to) or above 3 mg/L. The association between steady-state nevirapine concentrations and plasma HIV-1 RNA was determined by multivariate analysis. RESULTS: Out of 189 patients, 13 (7%) had low nevirapine plasma concentrations and 176 patients had concentrations above 3 mg/L. In total, 22 (12%) patients showed virological failure and 8 patients (4%) discontinued nevirapine because of adverse effects. The risk of failure in patients with nevirapine plasma concentrations </=3mg/L was increased (relative risk 5.0, 95% CI 1.8-13.7). Rashes and liver enzyme elevations each occurred in 8% of patients. CONCLUSIONS: Low nevirapine drug concentrations are predictive of virological failure.

Adult↗
PubMed2003

A once-daily HAART regimen containing indinavir + ritonavir plus one or two nucleoside reverse transcriptase inhibitors (PIPO study).

INTRODUCTION: There is an increased interest in developing once-daily regimens for the treatment of HIV-infected patients. A Phase II study was conducted to investigate the pharmacokinetics, and short-term safety and efficacy of an indinavir/ritonavir combination as part of a once-daily regimen. METHODS: HIV-infected patients with either proven poor compliance to HAART regimens in the past or an anticipated poor compliance to such a regimen in the future were eligible for this study. They received a once-daily regimen consisting of indinavir 1200 mg, ritonavir 400 mg, and one or two nucleoside reverse transcriptase inhibitors (NRTIs), also administered once daily with food. A 24 h pharmacokinetic profile was constructed in a subset of patients. Short-term safety and efficacy were evaluated at 4, 12 and 24 weeks after initiation of treatment. RESULTS: A total of 64 patients were included in this study, of whom 27 (42.2%) were treatment-naive. The geometric mean (+95% CI) of indinavir AUC0-24h, Cmax and Cmin as determined in an unselected group of 16 patients were 84.9 (69.7-103.5) mg/l x h, 12.0 (10.2-14.1) mg/l and 0.15 (0.09-0.26) mg/l, respectively. A large interpatient variability was observed, with five out of the 16 subjects having a Cmin value below the minimum effective concentration of 0.10 mg/l. During the 24 weeks of follow-up nine patients (14.1%) discontinued study medication, two due to medication-related toxicity. Gastrointestinal adverse events were reported most frequently (50.0%), followed by skin effects (45.3%), joint pain (9.4%) and urological complaints (7.8%). No patient developed nephrolithiasis. The median (+interquartile range) serum creatinine level in the 64 patients increased slightly from 74 (63-88) micromol/l to 79 (66-92) micromol/l during the 24 weeks of follow-up. One new patient reached a grade 1 elevation in serum creatinine, which normalized during the follow-up; five other patients with elevated serum creatinine at baseline remained stable. During the 24 weeks of follow-up, the proportion of patients with a viral load <500 copies/ml increased from 35.1% at baseline to 71.4% (ITT NC=F analysis) or 83.3% (OT analysis), and from 0% at baseline to 76.2% (ITT NC=F analysis) or 100.0% (OT analysis) in treatment-experienced and -naive patients, respectively. This was accompanied by a mean increase in CD4 cell count of 52 and 220 cells/mm3 in these two sub-groups, respectively. CONCLUSION: The 24-week follow-up data of this study indicate favourable pharmacokinetics of an indinavir/ritonavir 1200/400 mg combination as part of a once-daily regimen consisting also of one or two NRTIs. Short-term safety and efficacy were also satisfactory. Long-term follow up is planned to evaluate the durability of these results.

Adult↗
PubMed2002

Risk factors for urological symptoms in a cohort of users of the HIV protease inhibitor indinavir sulfate: the ATHENA cohort.

BACKGROUND: Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency. OBJECTIVE: To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use. METHODS: This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996. RESULTS: The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7; 95% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2; 95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4; 95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1; 95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9; 95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass. CONCLUSION: Increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environments.

Adult↗
PubMed2002

Low risk of treatment failure after substitution of nevirapine for protease inhibitors among human immunodeficiency virus-infected patients with virus suppression.

There is little information about the risk of treatment failure after a switch from human immunodeficiency virus (HIV) protease inhibitors (PIs) to nevirapine (Nvp) for patients with successful virus suppression. This study compared the 1-year risk of treatment failure for patients switching from a first PI-containing antiretroviral regimen to Nvp (Nvp group) with the risk for patients switching to second-line PIs (PI group) in the ATHENA (AIDS Therapy Evaluation, The Netherlands) study cohort (n=2470) whose HIV-1 RNA loads were < or = 500 copies/mL. Treatment failure was defined as measurement of HIV-1 RNA loads >500 twice or >10,000 copies/mL once or discontinuation of treatment for any reason. There were 446 eligible patients, 125 in the Nvp group and 321 in the PI group. The risk of treatment failure in the Nvp group, after data were adjusted for other risk factors, was 5-fold (95% confidence interval, 0.1-0.4) lower than the risk in the PI group, primarily because the discontinuation rate was lower. In patients with virus suppression, a switch to Nvp is more likely than a switch to second-line PIs to result in sustained virus suppression and maintenance of the new regimen.

Adult↗
PubMed2002

Determinants of recurrent toxicity-driven switches of highly active antiretroviral therapy. The ATHENA cohort.

BACKGROUND: Toxicity is the most important reason for premature switching of highly active antiretroviral therapy (HAART). In order to optimize the benefit-risk ratio of HAART, guidelines for toxicity management are needed. OBJECTIVE: An observational cohort study to estimate the incidence and identify determinants of toxicity-driven switches on second-line HAART after having switched first-line HAART despite successful viral suppression. METHODS: Patients were selected from those in the ATHENA cohort (n = 2470) who switched the initial HIV protease inhibitor (PI)-containing HAART while plasma HIV-1 RNA was <or= 500 copies/ml (n = 775). One-year cumulative incidences of subsequent toxicity-driven switches and adjusted relative risks (RR) for potential determinants were calculated. RESULTS: The 1-year cumulative incidence of toxicity-driven switches of the second regimen was 24% [95% confidence interval (CI), 21-28], mostly because of gastrointestinal toxicity and neuropathy. Those who had switched from first HAART because of toxicity were at an increased risk of a recurrent toxicity-driven switch (RR, 2.5; 95% CI, 1.7-3.5). Switching from PI to nevirapine while continuing the other antiretroviral drugs was more protective against a subsequent switch because of further toxicity than changing to another PI-containing regimen (RR, 0.2; 95% CI, 0.1-0.6). CONCLUSIONS: As for first-line HAART, toxicity is responsible for the majority of switches during second-line HAART. Prior switching for toxicity increased the risk of having to switch the subsequent regimen for toxicity, but this risk is reduced when switching to nevirapine rather than to an alternative PI. The latter should be taken into account when designing toxicity-management guidelines.

Adult↗