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Biomedical subjects

Christian Michelet

Publications and source records attributed to Christian Michelet.

24 records · Page 2Linked to original sources

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↗

Benefits of management strategy adjustments during an outbreak of enterovirus meningitis in adults.

Enteroviruses (EVs) are the most common identifiable cause of the aseptic meningitis syndrome. Widespread seasonal outbreaks of EV meningitis result in a high financial cost to the community, in part because of the difficulty of discriminating between viral and bacterial meningitis. During a nationwide outbreak of EV meningitis due to echovirus 30 in France we tested the hypothesis that a management strategy including early testing of cerebrospinal fluid (CSF) by means of EV PCR in all adult patients with acute aseptic meningitis on admission might reduce the duration of hospitalization and thus the expenditure on health resources. We compared the characteristics of adult patients with acute aseptic meningitis seen in our institution before (n = 21) and after (n = 27) implementation of this strategy. The strategy was cost-effective in that it significantly reduced (i) the mean duration of hospital stay (from 103 to 80 h; p = 0.04); and (ii) the mean duration of antibacterial treatment (from 115 to 69 h; p = 0.02). Systematic testing of CSF in adult patients with aseptic meningitis by means of EV PCR may be cost-effective during an outbreak of EV meningitis.

Adolescent↗

Simultaneous quantitative assay of six HIV protease inhibitors, one metabolite, and two non-nucleoside reverse transcriptase inhibitors in human plasma by isocratic reversed-phase liquid chromatography.

A rapid (less than 30 min), sensitive, and specific liquid chromatography method for simultaneous assay of nine antiretroviral drugs in human plasma is described. This technique allows therapeutic drug monitoring of six approved protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) and two approved non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine). Assays were performed after diethyl ether liquid-liquid extraction from 250-microL plasma samples. Chromatographic separation was achieved on an X-TERRA (Waters; Saint Quentin, France) column using a 58% water (with 3 mmol/L pyrrolidine) and 42% acetonitrile mobile phase. Three ultraviolet wavelengths were used for detection with a diode array detector. This method allowed quantitative assay of all nine antiretroviral drugs within a concentration range of 25 ng/mL to 9000 ng/mL. The method has been validated extensively and has been in routine use in our laboratory for several months for drug monitoring in plasma samples from patients treated with antiretroviral drugs.

Chromatography, High Pressure Liquid↗

Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.

OBJECTIVE: To evaluate the safety profile and efficacy of salvage regimens containing amprenavir (APV) 600 mg twice daily and ritonavir (RTV) 200 mg twice daily. DESIGN: Prospective, single-center study. METHOD: The patient database of the department of infectious diseases was screened for patients who had failed at least two successive three-drug combinations. These patients were proposed to take APV and RTV in association with two to four other drugs. They were followed monthly for 6 months. RESULTS: Seventeen patients were included. They had been previously treated for 70 +/- 23 months. At baseline, viral load (VL) was 4.86 +/- 0.98 log10 copies/mL and CD4 187 +/- 145 10(6)/L. On week 24, using intent-to-treat analysis, VL decreased to 2.95 +/- 1.59 log10 copies/mL and CD4 increased to 365 +/- 210 10(6)/L. Nine patients (53%) had a VL < 2.3 log10 copies/mL. The most common adverse events were grade 1 or 2 diarrhea and an increase of cholesterol and triglyceride levels. Mean APV trough concentration was 1727 +/- 1749 ng/mL on week 24. CONCLUSION: These data show that the combination of low-dose RTV and reduced doses of APV is safe. This combination can be added to nonnucleoside analogs.

Adult↗