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Biomedical subjects

Catherine Leport

Publications and source records attributed to Catherine Leport.

At least 19 recordsLinked to original sources
PubMed2003

Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.

The distribution of risk factors for cardiovascular disease in patients aged 35-44 years who were treated for human immunodeficiency virus type 1 (HIV-1) infection was compared with that for a population-based cohort. HIV-1-infected men treated with a protease inhibitor-containing regimen (n=223), compared with HIV-1-uninfected men (n=527), were characterized by a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol level, a higher prevalence of smoking, a higher mean waist-to-hip ratio, and a higher mean triglyceride level. No difference was found for total plasma or low-density cholesterol levels, nor for the prevalence of diabetes. Similar trends were observed among female subjects. The predicted risk of coronary heart disease was greater among HIV-1-infected men (relative risk [RR], 1.20) and women (RR, 1.59; P<10(-6) for both), compared with the HIV-1-uninfected cohort. The estimated attributable risks due to smoking were 65% and 29% for HIV-1-infected men and women, respectively. Because most HIV-1-infected people will ultimately need antiretroviral therapy, risk factors for cardiovascular disease should be determined at the initiation of treatment, and interventions should be considered for all patients who have them.

Adult↗
PubMed2003

The detection of non-adherence by self-administered questionnaires can be optimized by protease inhibitor plasma concentration determination.

Self-reported adherence and plasma protease inhibitor concentration (PPIC) were assessed in 642 HIV-infected patients at month 4 of a single protease inhibitor-containing regimen. PPIC was below the limit of quantification (LOQ) in 32% of non-adherent patients and in 8% of adherent patients. The relationship between non-adherence and a detectable HIV viral load was enhanced when adherent patients with PPIC below LOQ were considered to be non-adherent. PPIC combined with self-report may more reliably detect non-adherence.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Health-related quality of life after 1 year of highly active antiretroviral therapy.

OBJECTIVE: We investigated the impact of the first year of highly active antiretroviral therapy (HAART) on health-related quality of life (HRQL). METHODS: Medical data for patients in the French APROCO cohort were collected at enrollment (M0) and month 12 (M12). A self-administered questionnaire gathered information about HRQL (Medical Outcome Study 36-Item Short Form Health Survey) and toxicity-related symptoms. Using the twenty-fifth percentile of HRQL scales in the French population as a threshold, patients with normal values in at least three mental and three physical scales were considered to have a "normal HRQL." RESULTS. Of the 1053 patients followed through M12, HRQL data at M0 and M12 were available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%) experienced a deterioration of HRQL at M12. Among the 421 patients with a low baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that factors independently associated with a normal HRQL at M12 were normal baseline HRQL, baseline CD4 count <500 cells/mm, time since HIV diagnosis <8 years, undetectable HIV-RNA at M12, and lower number of self-reported symptoms at M12. CONCLUSION: An assessment of HRQL should be integrated to efficacy outcomes to evaluate and compare long-term strategies properly and to optimize the durability of response to antiretroviral therapy.

Adult↗
PubMed2003

Quantitation of cytomegalovirus (CMV) DNA by real-time PCR for occurrence of CMV disease in HIV-infected patients receiving highly active antiretroviral therapy.

In HIV-infected patients treated with highly active antiretroviral therapy (HAART) included in the Predivir cohort, we have evaluated the usefulness of CMV DNA quantitation by a TaqMan PCR assay from peripheral blood leukocytes (PBLs) to predict CMV disease occurrence. In parallel with the immune restoration after treatment by HAART, the percentage of positive samples decreased progressively from 7.3% at Day 0 to 3.5% at Month 12. Among the CMV markers, the smallest concordance with PBL CMV TaqMan PCR, as evaluated by kappa, was observed with pp65 antigenemia, whereas concordance with all other CMV markers was high. Among the 16 patients with CMV DNA copies at least once >100/150,000 cells, CMV disease occurred in six during follow-up, whereas among the 159 patients with CMV DNA copies always <10/150,000 cells, CMV disease occurred in three and among the seven patients with CMV DNA copies >10 and <100 occurred in only one. In univariate Cox models, all the CMV markers including PBL CMV TaqMan PCR >10/150,000 cells (RR: 27.6, IC95: 7.1-107.2), the CD4 cell count <75 cells/mm(3) and the HIV viral load >100,000 copies/ml were predictive for CMV disease. In a stepwise multivariate analysis, which should be interpreted with caution due to the small number of events (n = 10), three covariates were associated independently with CMV disease: pp65 antigenemia >100 nuclei/200,000, PBL CMV TaqMan PCR >10 copies/150,000 cells and HIV viral load remaining or increasing >100,000 copies/ml.

Adult↗
PubMed2003

Bivariate longitudinal model for the analysis of the evolution of HIV RNA and CD4 cell count in HIV infection taking into account left censoring of HIV RNA measures.

We present a bivariate linear mixed model taking into account censored measures of the response variable due to lower quantification limit of the assays. It allows an estimate of the correlation between the two response variables and takes into account this correlation for the estimation of other model parameters. This model was applied in a large cohort study (APROCO Cohort) to study the evolution under antiretroviral treatment of the two major biomarkers of the progression of Human Immunodeficiency Virus (HIV) infection: plasma HIV RNA and CD4+ T lymphocytes cell count. In a sample of 929 patients who started an highly active antiretroviral therapy, we illustrate the superiority in terms of likelihood of a bivariate model compared to two univariate models and the impact of taking into account the left-censoring of HIV-RNA. Moreover, interpretation of the model parameters allows confirmation of correlation between these two markers throughout the whole follow-up and the continuous decrease of plasma HIV RNA on average. Despite some limitations (distribution assumption, ignorance of missingness process), such a model appeared to be very useful to correctly describe the current evolution of important biomarkers in HIV infection.

CD4 Lymphocyte Count↗
PubMed2002

Mechanisms of early virologic failure in antiretroviral-naive patients starting protease inhibitor-containing regimens: the APROVIR Study.

The virologic and pharmacologic mechanisms of virologic failure (VF) were studied in 243 antiretroviral-naive patients starting first-line protease inhibitor (PI)-containing therapy (nelfinavir in 66% and indinavir in 19%). Among the 220 patients with follow-up data, VF occurred in 35 (16%) during the first year of follow-up. A higher baseline virus load and poorer adherence to therapy were associated with VF. At the time of VF, key PI-resistance mutations were detected in 11 (48%) of 23 patients who started on nelfinavir but were absent in 6 patients with indinavir treatment failure. PI plasma levels were more often below the range of active concentrations in VF with wild-type viruses (74%) than in VF with PI-resistant viruses (25%; P=.02). The mechanisms of early VF and of selection of PI-resistant viruses differed by type of PI and were dependent on PI plasma levels.

Adult↗
PubMed2002

Factors associated with mortality in human immunodeficiency virus type 1-infected adults initiating protease inhibitor-containing therapy: role of education level and of early transaminase level elevation (APROCO-ANRS EP11 study). The Antiprotéases Cohorte Agence Nationale de Recherches sur le SIDA EP 11 study.

This study attempted to identify factors associated with mortality among human immunodeficiency virus (HIV)-infected adults starting a protease inhibitor (PI)-containing therapy. Among 1155 patients consecutively enrolled in the APROCO study between May 1997 and June 1998, clinical characteristics were as follows: median age, 36 years; median baseline CD4 cell count, 288 cells/mm(3); and median baseline plasma HIV RNA load, 4.4 log(10) copies/mL. After a median follow-up of 27 months, 48 deaths had occurred, of which 44% were related to acquired immune deficiency syndrome. The mortality rate was 2.9% at 12 months. When both data at baseline and data at 4 months after the start of PI therapy were considered, factors independently associated with mortality were (Cox model) low baseline plasma creatinine level, low school education level, low CD4 cell count at 4 months, low hemoglobin level, and elevated hepatic transaminase levels. Thus, social context plus clinical and biologic data, including the 4-month response to treatment, must be considered in treatment of HIV-infected patients.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies.

BACKGROUND: Insufficient data are available from single cohort studies to allow estimation of the prognosis of HIV-1 infected, treatment-naive patients who start highly active antiretroviral therapy (HAART). The ART Cohort Collaboration, which includes 13 cohort studies from Europe and North America, was established to fill this knowledge gap. METHODS: We analysed data on 12,574 adult patients starting HAART with a combination of at least three drugs. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We considered progression to a combined endpoint of a new AIDS-defining disease or death, and to death alone. The prognostic model that generalised best was a Weibull model, stratified by baseline CD4 cell count and transmission group. FINDINGS During 24,310 person-years of follow up, 1094 patients developed AIDS or died and 344 patients died. Baseline CD4 cell count was strongly associated with the probability of progression to AIDS or death: compared with patients starting HAART with less than 50 CD4 cells/microL, adjusted hazard ratios were 0.74 (95% CI 0.62-0.89) for 50-99 cells/microL, 0.52 (0.44-0.63) for 100-199 cells/microL, 0.24 (0.20-0.30) for 200-349 cells/microL, and 0.18 (0.14-0.22) for 350 or more CD4 cells/microL. Baseline HIV-1 viral load was associated with a higher probability of progression only if 100,000 copies/microL or above. Other independent predictors of poorer outcome were advanced age, infection through injection-drug use, and a previous diagnosis of AIDS. The probability of progression to AIDS or death at 3 years ranged from 3.4% (2.8-4.1) in patients in the lowest-risk stratum for each prognostic variable, to 50% (43-58) in patients in the highest-risk strata. INTERPRETATION: The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART. Our findings have important implications for clinical management and should be taken into account in future treatment guidelines.

Adolescent↗
PubMed2002

Changing profile of infective endocarditis: results of a 1-year survey in France.

CONTEXT: Since the first modern clinical description of infective endocarditis (IE) at the end of the 19th century, the profile of the disease has evolved continuously, as highlighted in epidemiological studies including a French survey performed in 1991. OBJECTIVE: To update information gained from the 1991 study on the epidemiology of IE in France. DESIGN AND SETTING: Population-based survey conducted from January through December 1999 in all hospitals in 6 French regions representing 26% of the population (16 million inhabitants). PATIENTS: Three hundred ninety adult inpatients diagnosed with IE according to Duke criteria. MAIN OUTCOME MEASURES: Incidence of IE; proportion of patients with underlying heart disease; clinical characteristics; causative microorganisms; surgical and mortality outcomes. RESULTS: The annual age- and sex-standardized incidence was 31 (95% confidence interval [CI], 28-35) cases per million, not including the region of New Caledonia, which had 161 (95% CI, 117-216) cases per million. There was no previously known heart disease in 47% of the cases. The proportion of prosthetic-valve IE was 16%. Causative microorganisms were: streptococci, 48% (group D streptococci, 25%; oral streptococci, 17%, pyogenic streptococci, 6%); enterococci, 8%; Abiotrophia species, 2%; staphylococci, 29%; and other or multiple pathogens, 8%. Blood cultures were negative in 9% and no microorganism was identified in 5% of the cases. Early valve surgery was performed in 49% of the patients. In-hospital mortality was 16%. Compared with 1991, this study showed a decreased incidence of IE in patients with previously known underlying heart disease (20.6 cases per million vs 15.1 cases per million; P<.001); a smaller incidence of oral streptococcal IE (7.8 cases per million vs 5.1 cases per million; P<.001), compensated by a larger proportion of IE due to group D streptococci (5.3 cases per million vs 6.2 cases per million; P =.67) and staphylococci (4.9 cases per million vs 5.7 cases per million; P =.97); an increased rate of early valve surgery (31.2% vs 49.7%; P<.001); and a decreased in-hospital mortality rate (21.6% vs 16.6%; P =.08). CONCLUSION: Although the incidence of IE has not changed, important changes in disease characteristics, treatment, and outcomes were noted.

Adolescent↗
PubMed2002

Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039.

In this international, noncomparative, randomized phase II trial, we evaluated the effectiveness and tolerance of atovaquone suspension (1500 mg orally twice daily) plus either pyrimethamine (75 mg per day after a 200-mg loading dose) or sulfadiazine (1500 mg 4 times daily) as treatment for acute disease (for 6 weeks) and as maintenance therapy (for 42 weeks) for toxoplasmic encephalitis (TE) in patients infected with human immunodeficiency virus. Twenty-one (75%) of 28 patients receiving pyrimethamine (95% lower confidence interval [CI], 58%) and 9 (82%) of 11 patients receiving sulfadiazine (95% lower CI, 53%) responded to treatment for acute disease. Of 20 patients in the maintenance phase, only 1 experienced relapse. Eleven (28%) of 40 eligible patients discontinued treatment as a result of adverse events, 9 because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. Although gastrointestinal side effects were frequent, atovaquone-containing regimens are otherwise well tolerated and safe and may be useful for patients intolerant of standard regimens for toxoplasmic encephalitis.

AIDS-Related Opportunistic Infections↗
PubMed2002

Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy.

Morphologic and metabolic changes associated with protease inhibitor (PI) therapy have been reported since the introduction of PIs for treatment of human immunodeficiency virus infection. These changes were measured 12-20 months after initiation of PI therapy in a cross-sectional study involving 614 patients from the Antiprotéases Cohorte (APROCO) Study (Agence Nationale de Recherches sur le Sida-EP11). The prevalence was 21% for isolated peripheral atrophy, 17% for isolated fat accumulation, 24% for mixed syndrome, 23% for glucose metabolism alterations, 28% for hypertriglyceridemia (triglyceride level, > or =2.2 mM), and 57% for hypercholesterolemia (cholesterol level, > or =5.5 mM). Age was significantly associated with different phenotypes of lipodystrophy and metabolic alterations, but body-mass index, CD4(+) cell count, and type of nucleoside reverse-transcriptase inhibitor or PI received were not constantly associated with these changes. Furthermore, in all models tested, exposure to stavudine was associated with lipoatrophy and exposure of ritonavir was associated with hypertriglyceridemia. Detection and management of these disorders should be implemented to prevent further complications.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Predictors of long-term increase in CD4(+) cell counts in human immunodeficiency virus-infected patients receiving a protease inhibitor-containing antiretroviral regimen.

The temporal relationships between plasma human immunodeficiency virus (HIV) RNA levels and evolution of CD4(+) cell counts was studied, using a 2-slope longitudinal mixed model, in 988 patients prospectively enrolled at the initiation of a protease inhibitor--containing regimen of antiretroviral therapy. The short-term slope (baseline through month 4) for mean change in CD4(+) cell count was +21.2 cells/mm(3)/month, and the long-term slope (month 4 through month 24) was +5.5 cells/mm(3)/month. Compared with results from patients without viral response, the long-term slope was 2.5 cells/mm(3)/month higher in patients who had plasma HIV RNA levels of <500 copies/mL at month 4 (P <.001). It was significantly lower after a rebound in plasma HIV RNA level to > or = 500 copies/mL (P <.0001), varied according to plasma HIV RNA level at the time of rebound, and was negative only when the plasma HIV RNA level at rebound was > or = 10,000 copies/mL. If CD4(+) cell counts can remain elevated despite virologic treatment failure, such a discrepant response may be transient in patients who have a high plasma HIV RNA level at the time of treatment failure.

Adult↗
PubMed2002

[Intermittent fever of infectious origin].

Intermittent fever is rare during the course of infectious diseases but it represents a diagnostic and therapeutic challenge. The most frequent infectious causes of intermittent fever are focal bacterial infections, mainly infections localised to canals like urinary or biliary ducts or the colon and also infections of a foreign material. Other causes are less frequent, like infective endocarditis, tuberculosis, infections due to Yersinia enterocolitica or malaria, or exceptional like borreliosis, ratbite fever, chronic meningococcemia or chronic Epstein-Barr Virus infection. Careful anamnesis and clinical examination as well as a few simple complementary investigations, preferably performed during a febrile episode, are often sufficient to set the limits of possible further more complex investigations.

Bacterial Infections↗
PubMed2002

Predictors of virological rebound in HIV-1-infected patients initiating a protease inhibitor-containing regimen.

OBJECTIVE: To study the predictors of virological rebound in patients having early virological response to protease inhibitor (PI)-containing regimen. DESIGN AND METHODS: APROCO cohort study prospectively enrolled 1283 HIV-infected patients starting a PI-containing regimen in 1997-1999. Adherence to therapy was measured with self-administered questionnaires after 4 months of therapy (M4). Virological rebound was defined as a viral load (VL) > 500 copies/ml in patients having early virological response, defined as a VL < 500 copies/ml at M4. Predictors of time to virological rebound were studied with multivariate proportional hazards model. RESULTS: During a median follow-up of 20 months, virological rebound was observed in 32% of the 830 patients with early virological response. Virological rebound was more frequent when patients had received previous antiretroviral treatment [adjusted hazards ratio (HR) = 2.4; P < 0.0001], were younger (HR = 1.4 per each 10 years younger; P < 0.0001), had baseline CD4 cell count < 500 x 106/l (HR = 2.3; P < 0.001), had higher baseline VL (HR = 1.4 per each log10 copies/ml higher; P < 0.001), reported low adherence to therapy at M4 (HR = 2.1; P < 0.001) or had stopped PI at M4 (HR = 1.7; P = 0.04). CONCLUSION: Initiation of treatment at a stage of preserved immunity is associated with a more durable virological response under protease inhibitor. Every effort should be made to monitor and strengthen adherence to therapy, even in patients having early virological response.

Adult↗
PubMed2002

Bivariate linear mixed models using SAS proc MIXED.

Bivariate linear mixed models are useful when analyzing longitudinal data of two associated markers. In this paper, we present a bivariate linear mixed model including random effects or first-order auto-regressive process and independent measurement error for both markers. Codes and tricks to fit these models using SAS Proc MIXED are provided. Limitations of this program are discussed and an example in the field of HIV infection is shown. Despite some limitations, SAS Proc MIXED is a useful tool that may be easily extendable to multivariate response in longitudinal studies.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Adherence to highly active antiretroviral therapies (HAART) in HIV-infected patients: from a predictive to a dynamic approach.

To-date, most socio-behavioural research about HTV-infected patients' adherence to highly active antiretroviral therapies (HAART) has been based on cross-sectional studies. The French APROCO cohort gave us the opportunity to conjointly analyse the relationships between short-term adherence to HAART and HIV-infected patients' characteristics before initiation of treatment on the one hand, factors related to patients' subjective experience with HAART on the other hand. At the fourth-month follow-up visit (M4) after first prescription of HAART (M0), 26.7% of our sample of 445 patients self-reported non-adherence behaviour. Some patients' characteristics at M0 (younger age, poor housing conditions, lack of social support, and problems of adherence with previous antiretroviral regimens) were related to non-adherence at M4 in multivariate analysis. Non-adherence at M4 was, however, also related to the evolutions that affected a number of factors between M0 and M4: levels of depression, symptoms associated with treatment side effects, perception of individual state of health, beliefs towards effectiveness and toxicity of HAART. increases in alcohol and tobacco consumption, as well as contacts with other physicians than hospital HAART prescribers. Our prospective study brings additional evidence that even short-term non-adherence cannot be reliably predicted on the sole basis of a few a priori patient characteristics that clinicians could easily identify before initiation of HAART. It suggests that a dynamic approach to adherence, continuously monitoring the impact of experience with HAART on patients' daily lives, is needed for improving management of HIV/AIDS care.

Adult↗