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Biomedical subjects

Catherine Leport

Publications and source records attributed to Catherine Leport.

At least 19 recordsLinked to original sources
PubMed2007

Hair versus plasma concentrations as indicator of indinavir exposure in HIV-1-infected patients treated with indinavir/ritonavir combination.

Large intra-individual variability in plasma levels may limit the interest of therapeutic drug monitoring based on a single determination. Indinavir concentrations were determined both in plasma and hair samples, and correlated with concomitant plasma HIV-RNA in 43 HIV-infected patients. In multivariate analysis, significant association was found between HIV-RNA below 50 copies/ml and indinavir concentrations in hair but not in plasma, suggesting that hair concentrations gave more extensive information on drug exposure than a single plasma sample.

Antiretroviral Therapy, Highly Active↗
PubMed2006

Diabetes mellitus and infective endocarditis: the insulin factor in patient morbidity and mortality.

AIMS: To analyse the characteristics of infective endocarditis (IE) in patients with diabetes mellitus (DM), and to evaluate the prognostic significance of DM according to insulin use. METHODS AND RESULTS: A total of 559 patients with definite IE including 75 patients (13%) with DM (insulin use n = 22; oral antidiabetic n = 53) were evaluated. Comparison of insulin-DM, oral-DM, and non-DM patients showed an older age (66 +/- 13, 66 +/- 10, 58 +/- 17, respectively; P = 0.004) in DM patients, and more frequent IE on prosthetic valves (32, 11, and 15%, respectively; P = 0.068) in insulin-DM patients. Oral streptococci (0, 8, and 18%, respectively; P = 0.016) were less frequently the causative organism than staphylococci (64, 26, and 29%, respectively; P = 0.002) in insulin-DM patients. Vegetations, dehiscence, abscess, and regurgitation rates did not differ among the three groups, nor did cardiac surgery rates (32, 47, and 48%, respectively; P = 0.334), but in-hospital mortality was higher in insulin-DM patients (50, 19, and 15%; P < 0.001). In multivariable analysis, independently of other determinants of death (age, IE location, Staphylococcus aureus, history of heart failure, immunosuppression, creatinine serum), insulin-DM was a predictor of death (OR, 4.69; 95% CI, 1.77-12.44), whereas oral-DM was not. CONCLUSION: IE prognosis in insulin-DM patients is poor due to the coexistence of host and pathogen factors. Insulin-DM patients with IE may require specific management.

Aged↗
PubMed2006

Presence of numerous stop codons in HIV-1 reverse transcriptase proviral DNA sequences from patients with virological response to HAART.

The impact of proviral DNA reverse transcriptase mutations on virological failure was evaluated in 50 HIV-1 HAART-treated patients switching from a protease inhibitor to a non-nucleoside reverse transcriptase inhibitor. Neither the M184I/V mutation detected in 12 patients nor stop codons at tryptophane positions detected in 13 patients were associated with virological failure. Stop codons appeared under successful therapy in 12 patients. Their presence should be assessed in studies with higher statistical power.

Antiretroviral Therapy, Highly Active↗
PubMed2006

Factors associated with nonadherence to highly active antiretroviral therapy: a 5-year follow-up analysis with correction for the bias induced by missing data in the treatment maintenance phase.

This study aimed to identify factors associated with nonadherence during the maintenance phase of highly active antiretroviral therapy (months 12-60) in the Anti PROtease Cohort (APROCO) cohort after correcting for the bias due to missing outcome data. A Heckman 2-stage approach (generalized estimating equations probit model) was used to compare visits with moderate or poor adherence and visits with high adherence. Between months 12 and 60, at least 1 self-reported adherence measure was available for 970 of the 1110 patients with at least 12 months of follow-up (3889 visits with adherence assessments). Adherence was rated as high at 2466 visits, moderate at 1125, and poor at 298. After adjustment for "missingness," moderate and poor adherence were independently associated with age (younger), perceived treatment side effects, dosing frequency different from twice daily, and a protease inhibitor-based regimen. They were also associated with depression and lack of support from the main partner. High adherence was most likely among patients born outside the European Union. A comparison restricted to poor-adherence and high-adherence visits yielded a similar pattern of predictors. Adjusting for missing outcome data changed the predictor set. Reasons for nonadherence are multifactorial. Psychosocial interventions and the selection of the best-tolerated regimens are needed to improve long-term adherence of HIV-infected patients to their lifelong treatment.

Adult↗
PubMed2006

[Adherence intervention for HIV-infected patients receiving antiretroviral treatment. Implementation and initial assessment].

OBJECTIVE: To describe the implementation and initial results of a specific educational and counseling intervention to examine and improve adherence to antiretroviral therapy (ARV) in HIV-infected patients. METHOD: Four patient profiles were defined: 1) discontinuation and 2) failure: patients with virological failure (defined as two consecutive viral loads>200 copies/mL) at ARV discontinuation or under treatment, both seen after the fact; 3) preparation: naive patients seen before starting treatment, and 4) reinforcement: patients in treatment seen for counseling to prevent virological failure. A clinical psychologist, nurse and hospital pharmacist jointly conducted the session. Data collected include standardized information about the characteristics of HIV infection and ARV regimens, and demographic, behavioral, social and cultural indicators. CD4 cell counts and HIV viral loads were recorded at D0, M1, M3, M9 and M12. The effectiveness of the adherence intervention was defined separately for each patient profile based on some combination of taking or restarting an ARV regimen, virological response, and M12 follow-up. RESULTS: The study included 139 patients between November 1998 and April 2000. The intervention was defined as effective in 50% and 40% of the discontinuation (n=26) and failure (n=61) patients respectively, 84% of those with preparation profile (n=37) and 93% (14/15) of reinforcement patients. Only undetectable HIV viral load at M3 was significantly associated with the effectiveness of the adherence intervention for all 4 profiles. The preventive interventions (preparation and reinforcement) were less effective in patients from outside Europe (p=0.013). CONCLUSION: The adherence intervention was more effective in preventing virological failure than in restoring ARV effectiveness among patients who had already experienced virological failure. It should therefore be proposed primarily before starting ARV, to prevent failure in treatment-naive patients, especially those from outside Europe.

Adult↗
PubMed2005

Recommendations for the management of patients after heart valve surgery.

Approximately 50,000 valve replacement operations take place in Europe annually and almost as many valve repair procedures. Previous European guidelines on management of patients after valve surgery were last published in 1995 and were limited to recommendations about antithrombotic prophylaxis. American guidelines covering the broader topic of the investigation and treatment of patients with valve disease were published in 1998 but devoted relatively little space to post-surgical management. This document represents the consensus view of a committee drawn from three European Society of Cardiology (ESC) Working Groups (WG): the WG on Valvular Heart Disease, the WG on Thrombosis, and the WG on Rehabilitation and Exercise Physiology. In almost all areas of patient management after valve surgery, randomized trials and meta-analyses do not exist. Such randomized trials as do exist are very few in number, are narrowly focused with small numbers, have limited general applicability, and do not lend themselves to meta-analysis because of widely divergent methodologies and different patient characteristics. Recommendations are therefore almost entirely based on non-randomized studies and relevant basic science.

Anticoagulants↗
PubMed2005

Response to highly active antiretroviral therapy at 6 months and long-term disease progression in HIV-1 infection.

OBJECTIVE: To compare the long-term prognostic significance of different definitions of immunologic and virologic responses to highly active antiretroviral therapy (HAART) at 6 months. METHODS: This was a prospective study conducted in 68 French hospitals. HAART was initiated in 2236 protease inhibitor-naive patients included in the French Hospital Database on HIV. Multivariate Cox proportional hazard models measuring time from 6 months after starting HAART were used to compare the strength of the association between different definitions of immunologic and virologic responses at 6 months and subsequent progression to AIDS or death. The Akaike's Information Criteria were used to identify the most appropriate model. RESULTS: During a median follow-up of 58 months, 325 patients experienced an AIDS-defining event or died. The model that fitted best was the model in which the CD4 cell count and plasma HIV-1 RNA values attained at 6 months were considered. The risk of clinical progression at 5 years ranged from 7% (95% confidence interval [CI]: 4-10) in patients whose CD4 cell count at 6 months was >or=350 cells/microL and whose HIV-1 RNA concentration was <3 log10 copies/mL to 63% (95% CI: 52-75) in patients whose CD4 cell count at 6 months was <100 cells/microL and whose HIV-1 RNA concentration was >or=5 log10. CONCLUSIONS: Plasma HIV-1 RNA concentration and CD4 cell count should be taken into account independently when evaluating early response to treatment. The persistent impact of early response on clinical progression at 5 years emphasizes the major importance of the success of first-line HAART.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Mechanisms involved in the low-level regeneration of CD4+ cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads.

BACKGROUND: Persistent low CD4(+) cell counts are observed in 5%-27% of patients treated for human immunodeficiency virus (HIV)-1 infection despite their having prolonged undetectable plasma viral loads. METHODS: To understand the possible mechanisms of this discordant immunological situation, a prospective transsectional case-control study was designed. HIV-1-infected subjects who had a plasma viral load <200 copies/mL for >1 year were considered to be case patients if their CD4(+) cell count was <250/mm(3); control patients had CD4(+) cell counts >500/mm(3) and were matched by sex, age, and nadir CD4(+) cell count to case patients. T cell proliferation after stimulation with various antigens, T cell subset counts, T cell rearrangement excision circles (TRECs), T cells undergoing apoptosis, cytokines influencing apoptosis, and cellular proviral DNA and plasma viral RNA persistence were assessed. RESULTS: Compared with the 19 control patients, the 19 case patients had undistinguishable lymphoproliferative responses to candidin and cytomegalovirus, fewer naive CD4(+) cells (CD45RA(+)62L(+), 23%+/-13% vs. 47%+/-14%; P<.0001), lower thymic output (1.28 vs. 3.95 TRECs/microL of blood; P=.0015), increased cell death by apoptosis (spontaneous, 23.2%+/-8.3% vs. 11.9%+/-8.4% [P=.02]; Fas induced, 38.6%+/-13.7% vs. 16.4%+/-8.0% [P=.004]), higher levels of plasma soluble tumor necrosis factor receptor II (9.6 vs. 5.3 ng/mL; P=.0058), and undistinguishable plasma HIV-1 and cellular proviral DNA loads. CONCLUSIONS: The mechanisms responsible for the low-level regeneration of CD4(+) cells involve, at least, deficiency in the regeneration of central CD4(+) cells and excessive apoptosis.

Adult↗
PubMed2005

[Antiretroviral therapy for HIV-infected patients with schizophrenia. Coordinated multidisciplinary management (7 cases)].

OBJECTIVE: Schizophrenia might appear to be an obstacle to the initiation of and especially compliance with antiretroviral therapy for HIV-infected patients. The aims of this study were to describe the clinical, immunologic and virologic course after initiation of antiretroviral therapy in 7 HIV patients with schizophrenia (according to DSM-IV-R criteria), and to analyse the possibilities of an adequate antiretroviral therapy for those patients. OBSERVATIONS: Multidisciplinary management by specialists in infectious diseases, addiction-related disorders, treatment adherence and compliance, and psychiatrists, as well as social workers, home care agencies, and patient advocacy and assistance groups, was organized with coordinated medical-psychiatric follow-up at least once a month. The patients, 6 men and 1 woman, were aged from 26 to 48 years; schizophrenia had been diagnosed in 5 patients 6 months to 20 years before the HIV infection was discovered; diagnoses of both diseases were essentially simultaneous for the other 2. All patients took long-term neuroleptics for their schizophrenia. Two were active drug addicts who received drug substitution treatment. Before antiretroviral treatment began, 6 patients had advanced infection: stage C with peak CD4 cell counts ranging from 6 to 70/mm3; they began treatment with protease inhibitors between May 1996 and August 1997. The seventh patient was first seen during primary HIV infection in July 1998, and treatment began then. Response to antiretroviral treatment with protease inhibitors was slow for all patients, but viral load became undetectable for 6 of the 7, after 5 months to 4 years; 3 had opportunistic infections. Follow-up ended in January 2002: 5 patients still had undetectable viral loads,, with CD4 cell counts ranging from 45 to 1 000/mm3. One patient died from mixed terminal cirrhosis (alcohol abuse and hepatitis C); the viral load in another was only partially controlled (10 000 copies/ml), because of poor treatment adherence. CONCLUSION: Individuals with schizophrenia can respond well to antiretroviral treatment, although response may appear slow; they can adhere to complex treatment regimens as long as they receive well coordinated and sustained multidisciplinary support.

Adult↗
PubMed2005

[Myocardial localisation of tuberculosis: the diagnostic value of cardiac MRI].

INTRODUCTION: Tuberculosis can be responsible for myocardial damage, the frequency of which is probably underestimated because of the difficulty in its diagnosis. We studied the contribution of cardiac magnetic resonance imaging (MRI) in three patients. OBSERVATIONS: Three patients were treated for disseminated tuberculosis. They had moderate cardiac abnormalities (tachycardia, dyspnoea on effort). The electrocardiogram was normal in 2 patients and the echocardiography showed localized hyperkinesias. Cardiac MRI revealed intra-myocardial nodular gadolinium enhancement and hyperkinesias. The clinical outcome in the 3 patients was favourable following anti-tuberculosis therapy; one patient was also administered corticosteroids. DISCUSSION: Cardiac MRI is a non-invasive examination that brought important arguments for the diagnosis of tubercular myocarditis in the 3 patients.

Adrenal Cortex Hormones↗
PubMed2005

Health-related quality of life and health locus of control beliefs among HIV-infected treated patients.

OBJECTIVE: This study examined the relations between health locus of control (HLOC) beliefs and health-related quality of life (HRQL) in 302 HIV-infected patients enrolled in a French cohort, 44 months (M44) after they began highly active antiretroviral therapy (HAART). METHODS: HLOC beliefs were measured with the Multidimensional Health Locus of Control (MHLOC) scale and HRQL, with the Medical Outcome Study Short-Form Health Survey (MOS-SF-36). RESULTS: Internal HLOC beliefs at the initiation of treatment were associated with both physical HRQL in multivariate analysis, while chance HLOC beliefs on beginning HAART were associated with mental HRQL at M44. CONCLUSION: These findings suggest the importance of considering the psychological characteristics and psychosocial beliefs of patients at the initiation of ARV treatment to optimise the long-term HRQL of HIV-infected patient and to develop adaptive intervention on coping strategies.

Adult↗
PubMed2005

Communication of pharmacogenetic research results to HIV-infected treated patients: standpoints of professionals and patients.

The aim of pharmacogenetic studies is to adapt therapeutic strategies to individual genetic profiles, thus maximising their efficacy and minimising the likelihood of adverse side effects. Since the advent of personalised medicine, the issue of communicating research results to participants has become increasingly important. We addressed this question in the context of HIV infection, as patients and associations are particularly concerned by research and therapeutic advances. We explored the standpoints of both research professionals and participants involved in a pharmacogenetic study conducted in a cohort of HIV-infected patients. The setting of the research protocol was followed over a 2-year period. Participants' standpoints were collected through a questionnaire and interviews were conducted with research professionals. Of 125 participants, 76% wished to receive individual results and 71% wished to receive collective results; 39% did not know when results might be expected. Communication of global research results is a principle that is generally accepted by professionals. Concerning individual feedback, the professionals felt that it was necessary if it could be of direct benefit to the participant, but they expressed doubts for situations with no recognised benefit. Our results highlight the necessity to consider this issue in greater detail. We suggest the need to anticipate the debates concerning individual feedback, to differentiate between situations and the importance of further investigations on the opportunities and modalities of communication. Finally, our work emphasised the opposite pressures between the pursuit of scientific knowledge and the therapeutic orientation of clinical trials.

Attitude of Health Personnel↗
PubMed2005

Indinavir plasma concentration and adherence score are codeterminant of early virologic response in HIV-infected patients of the APROCO cohort.

To study the respective roles of indinavir concentrations and treatment adherence as predictors of early virologic response, we analyzed the patients of the APROCO cohort treated by indinavir 800 mg TID during the first 4 months. Minimum (Cmin), maximum (Cmax), and the ratio of the measured to expected concentrations (CR) were estimated for each patient at M4, from a population pharmacokinetic analysis of all data. The relationship among virologic success at M4 [plasma HIV RNA (VL) <500 copies/mL], baseline characteristics, estimated indinavir concentrations, and adherence score measured by a self-administered questionnaire, was analyzed by multivariate logistic regression. In the 216 studied patients, baseline median HIV RNA was 4.4 log10 copies/mL, and CD4 cell count was 309/mm. Virologic success was achieved in 195 (90%) patients; it was independently related to baseline viral load (OR = 0.524, CI 0.29-0.93; P = 0.03), antiretroviral treatment naive status (OR = 3.89, CI 1.29-11.76; P = 0.01), and indinavir Cmin (OR = 1.06, CI 1.02-1.10; P = 0.004) when adherence score was not included in the model, whereas full adherence was the only independent related factor when included in the model (OR = 8.8, 95% CI 2.85-27.3; P < 10). In the 168 fully adherent patients, virologic success was more frequent in patients with shorter duration of antiretrovirals at baseline (P = 0.03), lower baseline HIV RNA (P = 0.03), and higher indinavir CR (P < 10); the most discriminating Cmin cut-off was 194 ng/mL. Data on the relationship between indinavir plasma concentration and virologic success are therefore misleading without a concomitant assessment of adherence. These data suggest that any strategy of therapeutic drug monitoring must imply first a combined evaluation of plasma concentrations and adherence level and second an intervention target based on the results of both assessments.

Adult↗
PubMed2005

High variability of indinavir and nelfinavir pharmacokinetics in HIV-infected patients with a sustained virological response on highly active antiretroviral therapy.

OBJECTIVES: To describe plasma concentrations of indinavir alone or combined with ritonavir, and of nelfinavir and its active metabolite M8, and to measure their variabilities in HIV-infected patients treated with a stable antiretroviral regimen and experiencing a sustained virological response for at least 12 months. PATIENTS AND METHODS: In this prospective trial, blood samples were drawn during a 6-hour time interval between two doses at enrolment to assess protease inhibitor (PI) pharmacokinetic parameters, and 4 months later to assess plasma trough and peak concentrations. Safety and adherence assessments and laboratory data were collected during an 8-month period. PI pharmacokinetic characteristics were analysed using a non-compartmental approach. Inter- and intrapatient variabilities were estimated using a linear mixed-effect model. The impact of different covariates on plasma trough concentrations was investigated. Eighty-eight patients were analysed: 42 treated with indinavir and 46 with nelfinavir. RESULTS: The interquartile range (IQR) of the plasma trough concentration corrected for the sampling time (Ccalc) was 116-374 microg/L for indinavir alone and 163-508 microg/L for indinavir/ritonavir. Ritonavir significantly increased indinavir elimination half-life and plasma exposure. For nelfinavir, the IQR of Ccalc was 896-2059 microg/L for three-times-daily administration and 998-2124 microg/L for twice-daily administration. Variabilities were high for both PIs. Intrapatient variability for indinavir alone (and indinavir + ritonavir) was 76% (107%) and interpatient variability was 58% (10%) in adherent patients. Intrapatient variability for nelfinavir three times daily (and twice daily) was 41% (74%) and interpatient variability was 62% (50%). Intrapatient variability was lowered in patients with a high adherence level. CONCLUSION: Although performed in a homogeneous population, this study documented a high interpatient but also intrapatient variability of indinavir and nelfinavir pharmacokinetics, which should be taken into account when interpreting therapeutic drug monitoring. Once patients have reached a sustained virological response, plasma PI monitoring may have a limited impact.

Adult↗
PubMed2004

Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy.

Immune reconstitution inflammatory syndrome (IRIS) occurred in 16 of 37 antiretroviral-naive patients who were treated subsequently for tuberculosis and human immunodeficiency virus (HIV) type 1 infection. IRIS was related to increases in the CD4 cell percentage and in the ratio of CD4 cells to CD8 cells after 1 month of antiretroviral therapy and to dissemination of tuberculosis. These results have implications for the diagnosis of IRIS and the understanding of its pathogenesis.

Adult↗
PubMed2004

Incidence of and risk factors for adverse drug reactions in a prospective cohort of HIV-infected adults initiating protease inhibitor-containing therapy.

Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval [CI], 6.8-8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline characteristics, plasma human immunodeficiency virus RNA levels of >or=5 log(10) copies/mL (hazard ratio [HR], 1.5; 95% CI, 1.1-2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1-1.2), creatinine clearance levels of <70 mL/min (HR, 2.1; 95% CI, 1.2-3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8-3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2-2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.

Adult↗