Biomedical subjects

Rodolphe Thiébaut

Publications and source records attributed to Rodolphe Thiébaut.

26 records · Page 2Linked to original sources

PubMed2003

Time-updated CD4+ T lymphocyte count and HIV RNA as major markers of disease progression in naive HIV-1-infected patients treated with a highly active antiretroviral therapy: the Aquitaine cohort, 1996-2001.

In naive HIV-1 infected patients who start a highly active antiretroviral therapy (HAART), the relationship between time-updated CD4+ cell count, HIV RNA, and clinical progression (new AIDS-defining event or death) is incompletely understood. A 2-step statistical approach was adopted: first, modeling the evolution of the 2 markers taking into account left-censoring of HIV RNA and, second, studying their respective effect on clinical progression. The study sample consisted in 551 previously untreated patients of the Aquitaine Cohort who started their first HAART regimen between 1996 and 2000. During a median follow-up of 33 months, 46 patients experienced a new AIDS-defining diagnosis and 23 died. In multivariate survival analysis, time-updated CD4+ cell count (hazard ratio [HR] = 1.92 for 100 cells/mm3 lower, P < 10(-4) and HIV RNA (HR = 1.30 for 1 log(10) copies/mL higher, P = 0.04) on continuous scale were associated with clinical progression. When analyzing the effect of updated biomarkers using usual thresholds, the association with clinical progression was weaker for CD4+ but still significant (P = 0.007) whereas it remained only significant for updated HIV RNA above 4 log(10) copies/mL (P = 0.01). The prognostic information of updated HIV RNA adjusted on updated CD4+ is significant but depends on how the markers are taken into account. Clinical decisions and interpretation of clinical trial results must weigh the signification of each of these 2 biomarkers.

Adult↗

PubMed2003

Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study.

OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy. RESULTS: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (> or = 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (CI), 1.45-2.22], PI but no NNRTI (OR, 2.35; 95% CI, 1.92-2.87), or NNRTI + PI (OR, 5.48; 95% CI, 4.34-6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level. CONCLUSION: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.

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↗

PubMed2003

Bone marrow histopathologic and molecular staging in epidermotropic T-cell lymphomas.

This study was undertaken to determine the prognostic value of bone marrow histopathologic and molecular analyses in 53 patients with mycosis fungoides and 7 with Sézary syndrome. Bone marrow was involved in only 1 patient with Sézary syndrome, clinical stage IVA, before bone marrow biopsy. An ambiguous T-cell infiltrate was observed in 8 patients but was not associated with disease progression. The bone marrow specimen was normal in 51 patients. Monoclonality was detected in the skin specimen in 44 cases; an identical T-cell clone in the blood specimen was found in 21 of them and, in 16 of the 21 patients, in bone marrow specimens without histologic correlation. Multivariate analysis confirmed that clinical stage and detection by polymerase chain reaction of an identical T-cell clone in skin and blood specimens had an independent prognostic value. No further prognostic value was observed for the presence of a T-cell clone in bone marrow specimens. Our data do not support the need for bone marrow examination in patients with mycosis fungoides/Sézary syndrome.

Adult↗

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

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

Evaluation of cardiovascular risk factors in HIV-1 infected patients using carotid intima-media thickness measurement.

BACKGROUND: Highly active antiretroviral therapies (HAART) in HIV-infected patients are often associated with lipodystrophy syndrome and metabolic disorders. Atherogenic lipid profile could expose these patients to atheromatous cardiovascular disease. We describe carotid artery intima-media thickness (IMT), a surrogate marker of atherosclerosis, according to HIV status, antiretroviral treatment, lipodystrophy and conventional cardiovascular risk factors. METHOD: In a multicenter prospective cohort study we have surveyed HIV-infected subjects with a carotid IMT measurement by B-mode ultrasonography. We collected information on lipodystrophy clinical manifestations, age, gender, body mass index (BMI), smoking habits, alcohol intake, systolic blood pressure, HIV transmission category, AIDS stage, type and duration of HAART, CD4+ cell count, plasma HIV-1 RNA, glucose, insulin, total cholesterol and homocysteine. RESULTS: Four hundred and twenty-three HIV-infected patients were studied. The median carotid IMT measurement was 0.54 mm (range: 0.50-0.60). Lipodystrophy syndrome was diagnosed in 161 HIV-infected patients (38.1%). In univariate linear regression, IMT was significantly higher (P<0.05) with older age, male gender, higher body mass index, higher waist-to-hip ratio, increased systolic blood pressure, total cholesterol, glucose disorders and homocysteine, regular smoking and alcohol consumption, lipodystrophy and HAART. In a multivariate analysis, the effect of lipodystrophy and HAART disappeared after adjustment for other cardiovascular risk factors. CONCLUSIONS: It was concluded that only conventional cardiovascular risk factors are independently associated with increased IMT in HIV-infected patients.

Adult↗

PubMedDate not supplied

Analysis of undetectable HIV RNA using survival analysis: results must be interpreted carefully.

This methodological note exemplifies the drawbacks of conventional survival analysis for studying the determinants of the evolution of HIV RNA after the initiation of a HAART regimen in observational cohort studies. The potential for loss of information might yield differential misclassification biases and therefore unreliable results. Longitudinal models are better suited to analyze the repeated measures of a continuous outcome such as HIV RNA.

Antiretroviral Therapy, Highly Active↗