Biomedical subjects

Henri Portier

Publications and source records attributed to Henri Portier.

27 records · Page 2Linked to original sources

PubMed2002

The evolution of hepatitis B virus serological patterns and the clinical relevance of isolated antibodies to hepatitis B core antigen in HIV infected patients.

BACKGROUND/AIMS: The evolution of hepatitis B virus (HBV) serological patterns and the clinical relevance of isolated anti-HBc pattern are not well established in HIV infected patients. METHODS: A cohort of 240 patients was followed for 6.9+/-3.4 years, with iterative HBV serologic assays performed (mean interval of 2.2 years). RESULTS: Five patients without HBV markers at baseline subsequently developed positive anti-HBs (incidence 0.66/100 patient-year), as did two patients with chronic HBs antigenemia (incidence 1.66/100 patient-year). Only one patient with isolated anti-HBc pattern developed HBs chronic antigenemia. Persistent isolated anti-HBc pattern was observed in 37 patients (13 with detectable blood HBV DNA) and was strongly associated with positive hepatitis C virus (HCV) viremia (hazard ratio=9.5, confidence interval 95%: 4.5-20.0, P<0.0001). Hepatic lesions were more severe in HCV infected patients with persistent isolated anti-HBc pattern than in those without (Knodell score 9.2+/-4.6 versus 6.7+/-5.0, P=0.04). In time updated analysis, this pattern was not associated with an increased risk of hepatotoxicity, by contrast with HCV infection or positive HBs antigenemia. CONCLUSIONS: In HIV infected patients, HBV serological status must be systematically and regularly assessed, and systematic HBV vaccination must be proposed in those without HBV marker. Isolated anti-HBc pattern must be considered in the management of hepatitis C, but not for antiretroviral therapy.

Adult↗

PubMed2002

Five day clarithromycin modified release versus 10 day penicillin V for group A streptococcal pharyngitis: a multi-centre, open-label, randomized study.

OBJECTIVE: A multicentre, comparative, randomized, open-label, Phase III trial evaluated the efficacy and tolerability of clarithromycin modified release (MR) versus penicillin V for pharyngitis due to group A beta-haemolytic streptococci (GABHS). METHODS: Three hundred and forty-nine patients (12-40 years) with acute pharyngotonsillitis and a positive Streptococcus A antigen immunoassay test were randomized to receive clarithromycin MR 500 mg od for 5 days or penicillin 590 mg tds for 10 days. Patients were clinically evaluated and a throat swab for culture obtained before treatment, after treatment (day 8 or 13 depending on the treatment arm) and at the follow-up visit (day 30). The main criterion for efficacy was the bacteriological cure rate after treatment. RESULTS: Three hundred and forty-nine patients were considered for the intent-to-treat analysis. After treatment, clinical cure rates were 88.1% in the clarithromycin group and 92.4% in the penicillin group, and eradication rates were 82.8% and 83.6%, respectively. There were no statistically significant differences between the two treatments. Three hundred and three (87%) patients had a positive culture before treatment, among which 29 (9.7%) were found to be clarithromycin resistant. Two hundred and thirty-nine patients were clinically and bacteriologically evaluable for per protocol analysis. After treatment, clinical cure rates were 95.2% in the clarithromycin group and 97.3% in the penicillin group, and eradication rates were 94.4% and 92%, respectively. No statistically significant difference was shown. Adverse events occurred in 46 patients of the clarithromycin group and 31 of the penicillin group (with no statistical difference). Most of them were of mild or moderate severity. CONCLUSION: Clarithromycin MR administered once daily for 5 days is as safe and effective as penicillin V administered three times a day for 10 days in the treatment of GABHS pharyngitis.

Adolescent↗

PubMed2002

Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin on experimental pneumonia induced with penicillin-resistant pneumococci with various susceptibilities to fluoroquinolones.

Newer fluoroquinolones, such as levofloxacin, have shown an enhanced in vitro and in vivo activity against penicillin-resistant Streptococcus pneumoniae infections. The frequency of S. pneumoniae with reduced susceptibility to quinolones, although currently low, raises the question of the therapeutic efficacy of levofloxacin on infection due to such strains. We used an animal model of penicillin-resistant pneumococcal pneumonia using six strains with various levels of susceptibility to ciprofloxacin and levofloxacin in rabbits to induce pneumonia, and simulated a human-like treatment of 500 mg twice a day for 48 h. Strains' susceptibility profiles for ciprofloxacin and levofloxaxin were (ciprofloxacin/levofloxacin MIC, mg/L; genotype): 0.5/0.5 (Cip0.5), 2/1 (Cip2), 4/1.75 (Cip4), 8/1.75 (parC mutation) (Cip8), 10/2 (parC mutation) (Cip10), 64/16 (parC and gyrA mutations) (Cip64), respectively. All the strains induced a crude pneumonia in all rabbits. Significant bacterial reductions at the end of treatment in lung and spleen were observed for the four former strains (P < 0.05) but not for the latter two. An AUC/MIC ratio of at least 32 identified 95% of an at least bacteriostatic effect (P = 0.038) and 76% of a bactericidal effect (P = 0.09). Mutants were detected in treated animals infected with strains harbouring parC mutations (Cip8 and Cip10) and when the AUC/MIC ratio was between 13 and 31. We conclude that levofloxacin is effective against experimental pneumonia due to pneumococci with MIC < 1.5 mg/L, ineffective on experimental pneumonia due to pneumococci with MIC > or = 2 mg/L, and could be associated with the appearance of mutants when a parC mutation is pre-existing.

Animals↗

PubMed2002

New model of ventilator-associated pneumonia in immunocompetent rabbits.

OBJECTIVE: Despite the high rate of therapeutic failures in ventilator-associated pneumonia, up to now there has been no animal model specifically designed for antimicrobial evaluation. A rabbit model of ventilator-associated pneumonia is described for the first time in this study. DESIGN Prospective, randomized experimental study. SETTING: An animal research laboratory. SUBJECTS: Male New Zealand healthy rabbits (n = 44). INTERVENTIONS: After oral intubation and an hour of mechanical ventilation, animals in the ventilator-associated pneumonia group (n = 22) were infected intrabronchially with a calibrated inoculum of. The nonventilated pneumonia group (n = 22) was composed of animals that received the same inoculum in the absence of mechanical ventilation. Rabbits from both groups were randomly killed 3, 6, 12, 24, or 48 hrs after inoculation. Pneumonia evaluation was based on histologic (macroscopic and microscopic score) and bacteriologic (bacterial count) findings. MAIN RESULTS: Infected animals undergoing mechanical ventilation rapidly developed a progressive bilateral and multifocal pneumonia. Lung bacterial mean (sd) concentration was 6.48 (0.71) log10 colony-forming units (cfu) per gram of tissue at the 48th hour, whereas bacteremia occurred in most cases. In the nonventilated pneumonia group, pneumonia was less severe in terms of bacterial count (3.18 [1.86] log10 cfu/g; p <.05), and spleen cultures remained negative. In addition, microscopic examination revealed noninfectious lung injury in the ventilator-associated pneumonia group, especially hyaline membrane filling alveolar spaces. Of note, these features were never observed in the nonventilated pneumonia group. CONCLUSIONS: An animal model of ventilator-associated pneumonia was obtained in immunocompetent rabbits. Histopathologic and bacteriologic features were similar to those found in humans. Obviously, pneumonia was more severe when animals underwent mechanical ventilation, especially in terms of systemic spread. Noninfectious lung injury corresponding to ventilation-induced lung injury may explain the difference. This model emphasizes the strong impact of both mechanical ventilation and infection on lung because they seem to act synergistically when causing alveolar damage. Moreover, it seems well suited to testing antimicrobial effectiveness.

Animals↗

PubMed1997

Efficacy of 5-day cefpodoxime proxetil for recurrent pharyngitis in adults. A comparative study with 10-day penicillin V or amoxycillin---clavulanate.

OBJECTIVE: To compare the clinical and bacteriologic efficacy of a 5-day course of cefpodoxime proxetil (CPD) with that of a 10-day course of penicillin V (PNV) or amoxycillin---clavulanate (AMC) in recurrent pharyngitis in adults. A cost-effectiveness study (reported elsewhere) was carried out at the same time. METHODS: This multicenter, randomized, open label trial involved 580 adult patients consulting general practitioners for clinical recurrent pharyngitis (greater-than-or-equal3 episodes within the last 12 months) regardless of the bacterial etiology. Patients were treated for 5 days with CPD, 100 mg twice daily, or for 10 days with PNV, 1x106 IU three times a day, or for 10 days with AMC, 500 mg (amoxycillin) three times a day. Clinical and bacteriologic outcomes were noted at the end of treatment, and cases of clinical recurrence were recorded during a 6-month follow-up period. RESULTS: At the end of treatment, clinical response was satisfactory in 157 of 170 (92.3%) patients on CPD, 147 of 166 (88.5%) patients on PNV, and 168 of 177 (94.9%) patients on AMC. Group A beta-hemolytic streptococci (GABHS) were eradicated in 22 of 23 (95.65%) patients on CPD, 16 of 16 (100%) patients on PNV, and 19 of 20 (95%) patients on AMC. The rates of clinical success and GABHS eradication were not significantly different between the groups. Compliance (p<0.001) and tolerance (p<0.001) were significantly better in the CPD group than in the other two groups. Among the 389 patients evaluable 6 months after the end of treatment, the recurrence rate of acute pharyngitis (due to any bacterium) was significantly lower in the CPD group (p=0.01 versus PNV; p<0.01 versus AMC). A Kaplan---Meier analysis (469 patients over 6 months) of the rate of non-recurrence, with comparison by the log-rank test, also showed a significant difference in favor of CPD. CONCLUSIONS: A 5-day treatment of recurrent pharyngitis with CPD was as effective and better tolerated than a 10-day treatment with PNV or AMC. The risk of recurrence was lower with CPD.

Journal Article↗

PubMed1997

Toxicity and efficacy of conventional amphotericin B deoxycholate versus escalating doses of amphotericin B deoxycholate---fat emulsion in HIV-infected patients with oral candidosis.

BACKGROUND: Amphotericin B deoxycholate remains the treatment of choice for most systemic fungal infections; however, its clinical use can be limited by infusion-related side effects and nephrotoxicity. New formulations of amphotericin in lipid compounds have been shown to decrease toxicity. We previously showed that a lipid emulsion preparation of amphotericin B deoxycholate was better tolerated than the conventional preparation in dextrose. Therefore, we have now studied the clinical tolerance, renal toxicity and efficacy of higher doses of amphotericin B deoxycholate prepared and infused in a fat emulsion (Intralipid 20%). Thus, this report adds information to the previous publication. METHODS: Forty-two patients infected with HIV and suffering oral candidosis entered the study. The patients received either amphotericin B deoxycholate---glucose 1 mg/kg/day or amphotericin B deoxycholate---lipid emulsion 1 mg/kg/day for 4 days (randomized phase), or amphotericin B deoxycholate---lipid emulsion 2 mg/kg/day or 3 mg/kg/day (escalating-dose phase) for 5 days. Clinical (immediate) side effects and renal (creatinine) tolerance were assessed daily; efficacy against oral candidosis was measured by using a simple clinical score. Serum levels of amphotericin B were also measured. RESULTS: None of the patients receiving amphotericin B deoxycholate---lipid emulsion had treatment interrupted, as compared to four (36%) in the amphotericin B deoxycholate---glucose group (pless-than-or-equal0.01); chills during or after the infusions were significantly less frequent in the amphotericin B deoxycholate---lipid emulsion groups than in the amphotericin B deoxycholate-glucose group (p=0.03). The increase of creatininemia during treatment was significantly higher for patients receiving amphotericin B deoxycholate---glucose than for those receiving amphotericin B deoxycholate---lipid emulsion (p=0.001). The number of patients who had a creatininemia greater-than-or-equal18 mg/L during treatment was significantly higher in both the amphotericin B deoxycholate---glucose group (36%) and in the group receiving the highest dose of amphotericin B deoxycholate---lipid emulsion than in other groups (pless-than-or-equal0.06). The serum concentrations of amphotericin B were lower for the amphotericin B deoxycholate---lipid emulsion regimen than for the amphotericin B deoxycholate---glucose regimen at the same dose of 1 mg/kg/day, but increased with the dose. The change of the oral candidosis score was similar for the same dose of 1 mg/kg/day of amphotericin B deoxycholate infused in either glucose or lipid emulsion; higher doses of amphotericin B deoxycholate---lipid emulsion were more efficacious (p=0.009) and this efficacy seemed to increase with the dose (p=0.06). CONCLUSIONS: The clinical and renal tolerance of amphotericin B deoxycholate are improved when the drug is directly prepared and infused in lipid emulsion (Intrapid) and this preparation allows for greater dosage, up to 3 mg/kg/day, with resultant greater efficacy. This preparation is simple and cost-effective (approximately 7 US $ per 50 mg of amphotercin B) and could be clinically compared to other formulations of amphotericin B.

Journal Article↗

PubMedDate not supplied

Acute liver enzyme elevations in HIV-1-infected patients.

BACKGROUND: Acute liver enzyme elevations (ALEE) have been associated with a first-line highly active antiretroviral therapy (HAART) and/or viral hepatitis coinfections in HIV-infected patients. By comparison, the frequency and the risk factors of ALEE in untreated patients and in patients treated with several antiretroviral regimens need to be assessed. PURPOSE: To describe the long-term frequency and the characteristics of ALEE in antiretroviral treated and untreated patients and to define risk factors for ALEE in a retrospective cohort of HIV-1-infected patients. METHOD: An HIV-infected cohort was retrospectively examined. ALEE was defined as levels of alanine amino transferase and/or alkaline phosphatase rising to at least 2.5 times above baseline values. Hazard ratios (HR) for ALEE were estimated using an extension of the Cox proportional model taking into account recurrent events. RESULTS: Out of 239 assessable patients, 12 (5%) were coinfected with hepatitis B virus (HBV) and 34 (14.2%) with hepatitis C virus (HCV). The incidence rate of ALEE was 9.9/100 patients-year and the cumulative incidence was 20.9%. HCV genotype 3 tended to give a higher risk of ALEE. Independent factors for developing ALEE in multivariate logistic regression were HBV (HR = 4.0) and HCV (HR = 3.4) coinfections, antiretroviral therapy (HR = 2.6), CDC stage C (HR = 2.5), and high alkaline phosphatase baseline values (HR = 1.7). CONCLUSION: The occurrence of ALEE is influenced more by the past medical history and the clinical background of the patients than by antiretroviral therapy. These patient-linked variables must be taken into account to avoid unwarranted treatment withdrawal.

Acute Disease↗

PubMedDate not supplied

Concentration of circulating oxidized LDL in HIV-infected patients treated with antiretroviral agents: relation to HIV-related lipodystrophy.

BACKGROUND: Circulating oxidized LDL (ox-LDL) is associated with clinical manifestations of atherosclerosis. The aim of the study was to investigate the concentrations of ox-LDL in HIV-infected patients under antiretroviral therapy with (HIV-LD) or without (HIV-nLD) HIV-related lipodystrophy. METHOD: A total of 44 HIV-infected men were enrolled in the study. Half of them had HIV-LD. The control group included 12 age- and body mass index (BMI)-matched HIV-uninfected men. Ox-LDL concentration and C-reactive protein level were determined. Insulin sensitivity was measured using the homeostasis model assessment (HOMA-IR). LD was assessed by using a validated score calculated from clinical and biological data. RESULTS: HIV-infected patients had significantly higher ox-LDL concentrations when compared to HIV-negative controls (0.8 +/- 0.3 mg/dL vs. 0.60 +/- 0.1 mg/dL; p = .007). HIV-LD patients had significantly higher ox-LDL concentrations than HIV-nLD patients (0.91 +/- 0.38 and 0.69 +/- 0.16; p = .04). In HIV-LD patients, current therapy with protease inhibitors (PIs); duration of PI therapy; HOMA-IR; and time exposure to stavudine, efavirenz, ritonavir, saquinavir, and amprenavir were significantly higher than in HIV-nLD patients. In multivariate analysis, time exposures to stavudine and ox-LDL concentration were independently related to lipodystrophy. CONCLUSION: The high concentration of ox-LDL was found in HIV-infected patients under antiretroviral therapy, especially in those with lipodystrophy.

Anti-Retroviral Agents↗

PubMedDate not supplied

Usefulness of therapeutic drug monitoring of antiretrovirals in routine clinical practice.

BACKGROUND: Clinical trials have shown that therapeutic drug monitoring (TDM) of antiretrovirals (ARV) improves patient care. However, little is known about the usefulness of TDM in routine practice. METHOD: We reviewed all the trough concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors that were performed for therapeutic failure, suspected drug toxicity, or routine purposes. RESULTS: Between 1998 and 2001, 146 TDMs were done in 109 HIV patients. Of the 48 patients with therapeutic failure, 62% had resistance to ARV with adequate ARV concentrations, 16% had insufficient drug exposure without any ARV resistance mutations, and 16% combined both resistance and suboptimal drug concentrations. Subsequent therapeutic interventions (increasing adherence and/or changing HAART) resulted in an undetectable viral load in 37.5% of the patients (14/48). Five (24%) of 21 patients with suspected drug toxicity had high drug concentrations associated with side effects. In all the cases, adverse events regressed after reduction of drug dosage. Of the 77 TDMs done for routine purposes, 26% were outside the therapeutic range. CONCLUSION: The data show that TDM of ARVs in the clinical setting provides important information that can be used to improve the management of HIV patients receiving antiretroviral therapy.

Diagnostic Tests, Routine↗