Abstract des Travaux Scientifiques

Do viral load and CD8 cell count at initiation of tritherapy influence the increase of CD4 T-cell count?Keita-Perse O, Roger PM,Pradier C, Pugliese P, Cottalorda J, Dellamonica P. AIDS 1998 Oct 22;12(15):F175-9


BACKGROUND:
Tritherapies including protease inhibitors improve clinical status and usually increase CD4 T cell count. However, the dissociation between the marked decreases in viral load and the  incomplete restoration of CD4 cell counts with a three-drug combination has been reported. We  assessed this potential difference among our patients.
METHODS
Patients were enrolled when a protease inhibitor was prescribed to them for the first time. Using a computerized medical record (ADDIS), we retrospectively assessed a potential relationship between the increase in CD4 T cells (deltaCD4) at M3, M6 and variables including sex, age, CDC staging, protease inhibitor, prior antiviral therapy, CD8 and viral load at baseline. We used Epi-Info 6.4 and BMDP software.
RESULTS:
Data were analyzed on 154 patients. The median CD4 T cell count was 157 at baseline, 215 at month 3 and 202 at month 6. The median viral load was 52000 copies at baseline, 530 at month 3 and 500 at month 6. In a univariate analysis, a significant relationship was found between deltaCD4 and CD8 at baseline. A statistically significant negative correlation appeared between the CD8 cell count at baseline and deltaCD4 at M6 (r=-0.28, Pearson). Moreover, we found that there also was a relationship between deltaCD4 and viral load at baseline. There was a correlation between deltaCD4 at M6 and the viral load at M0 (r=0.37, Pearson). In a multiple regression model, after CD8 count at baseline had been accounted for, we found a significant correlation between deltaCD4 and viral load at baseline (multiple r=0.33 at M3, and 0.40 at M6).
CONCLUSIONS:
Patients with a low viral load do not benefit from as great an increase in CD4 T cell count as others when they receive a tritherapy including protease inhibitors. These results suggest that another mechanism rather than direct viral pathogenicity leads to CD4 T cell destruction. This mechanism may not be efficiently stopped by antiviral therapy, especially protease inhibitors.
 
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Improving patients' enrollment into clinical trials: the experience of a computerized medical record (ADDIS).
Pugliese P; Wehrlen S; Pradier C; Keita-Perse O; Chambon JF; Mousnier A; Dellamonica P
Int Conf AIDS. 1998;12:814 (abstract no. 42207).


OBJECTIVES
to assess the efficacy of an expert system implemented in a computerized medical record in order to facilitate patients' enrollment into clinical trials and to avoid inadequate antiretroviral prescriptions.
METHODS:
We compared the number of patients enrolled in A.N.R.S. clinical trials and the rate of errors in antiretroviral prescriptions before and after implementation of an expert system. This expert system automatically suggests patients' enrollment into specific clinical trials or cohort studies on the basis of patient's current and prior treatment, CDC stage, CD4 cell-count and HIV viral load. Moreover it displays a warning signal before printing antiretroviral prescriptions (after comparison with guidelines).
RESULTS:
ADDIS has been operating since 1994 with a total of 1283 patients and 5860 records. Two 5-month periods were compared. The number of enrollments into A.N.R.S clinical trials increased (from 14 to 59). Moreover the prescriptions error rate was 6% before the expert system implementation and 0% after.
CONCLUSIONS:
Our computerized HIV medical record (ADDIS) already improves quality of care through its user-friendly  interface and numerous capabilities. It now allows physicians to be more aware of possibilities of enrollment into clinical trials or cohort studies and improves safety for antiretroviral prescriptions.

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Persistence of Pneumocystis carinii after effective treatment of P. carinii pneumonia is notrelated to relapse or survival among patients infected with human immunodeficiency virus.
Roger PM; Vandenbos F; Pugliese P; De Salvador F; Durant J; Le Fichoux Y;Dellamonica P
Clin Infect Dis. 1998 Feb;26(2):509-10.
  


Objective:
To determine the clinical relevance of the recovery of Pneumocystis carinii (PC) after treatment for acute Pneumocystis carinii pneumonia (PCP).
Methods:
Retrospective study of HIV-patients who were successfully treated for a first documented PCP and who benefit from a second broncho-alveolar lavage (BAL2).
Results:
Fifty-three patients, 38 male and 15 female (mean age 36 plus or minus 10 years) were eligible. Risks factors for HIV were IVDA: 23 patients (pts) heterosexuality: 16 pts, homosexuality: 12 pts and transfusion: 2 pts. Before diagnosis of PCP, 12 pts were on stage C but all had CD4 count less than 200/mm(3). Thirty-seven pts had not received primary prophylaxis against PCP, 15 pts had aerosolized pentamidine, 1 pt cotrimoxazole. This last drug was used as first-line treatment in all cases. Twenty height pts received steroid therapy for severe hypoxaemia. Twenty-three pts had adverse effects and required alternative treatment. BAL2 was conducted on day 21 plus or minus 4 after initiation of specific therapy. PC was still detectable in 34 pts (65%). Its presence was correlated with CD4 count: 36 plus or minus 39/mm(3) vs 69 plus or minus 47/mm(3) in case of negative BAL2 (p=0.012) and not with the severity of PCP nor with the need for steroid or second-line treatment. Four pts were readmitted for PCP at month 7, 8, 20 and 22 respectively; two of them had positive BAL2. All of these 4 pts had received pentamidine aerosol as secondary prophylaxis. Twenty height pts are alive at the time of study end point with a mean follow up of 19 plus or minus 13 months; mortality did not appear to be related to the positive result of LBA2: 22 pts died vs 10 for negative BAL2.
Conclusions:
1) PC on follow up BAL is frequently observed; 2) Positive BAL2 is related to immunological status; 3) Positive BAL2 is not predictive of recurrence or shortened survival; and 4) in the absence of clinical improvement during PCP treatment, persistent PC is generally not indicative of ineffective therapy and another aetiology must be sought.

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Dossier médical informatisé pour les patients atteints d’infection par le VIH (ADDIS) : l’expérience du Service des Maladies Infectieuses du CHU de Nice.
Pradier C, Pugliese P, Caissotti C, S Wehrlen-Martini, Huynh-Van E, Pueyo B, Dellamonica P.
Méd Mal Inf. 1998 ;28 :291-5.

Objectif
Créer un dossier médical informatisé pour améliorer la qualité de la prise en charge médicale des patients infectés par le VIH, faciliter la communication entre les différents intervenants et constituer une base de données utiles à la recherche et à l’évaluation des pratiques médicales. Le projet est en cours dans le Service des Maladies Infectieuses et Tropicales du professeur Dellamonica au CHU de Nice, qui a une file active annuelle de 940 patients.

Méthode
Afin de faciliter l’acceptation des changements inhérents à la mise en place du logiciel, les référents du projets ont réalisé une maquette conviviale, simple d’utilisation, compatible avec les bases de données existantes, et évolutive (système de gestion des données DB2/2; système d’exploitation et de gestion des écrans: OS/2 V2.1 avec CM2). Les utilisateurs ont apporté des améliorations à la version initiale du logiciel, qui a ensuite été installée dans les unités de soins. Des modifications ont été alors réalisées sur site en fonction des remarques soulevées par les premiers utilisateurs.

Résultats
Le logiciel est fonctionnel depuis juin 1994 (1283 patients, 5860 recours). Il permet la saisie en temps réel des données par les médecins et l’envoi des informations par des interfaces, vers les bases de données interne et externes (PMSI, DMI-2). Il crée les ordonnances de prescription et les lettres pour les médecins de ville. Des projets de recherche sont en cours à partir des données recueillies.

Conclusions
Le logiciel ADDIS est bien accepté par l’équipe médicale du fait de sa simplicité d’utilisation et de ses nombreuses fonctionnalités. La fiabilité des informations recueillies permet d’utiliser les données à des fins de recherche et d’évaluer les pratiques médicales. L’extension du logiciel pour d’autres pathologies que l’infection par le VIH est envisagée.

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Relationship between immune status and histological course of hepatitis C in HIV-infected patients.
Pierre-Marie R; St Paul MC; Pugliese P; Fuzibet JG; Mondain V; Michiels JF; Dellamonica P
Int Conf AIDS. 1996 Jul 7-12;11(1):301 (abstract no. Tu.B.2210).

Objective:
To determine the influence of immune status on the histological lesions of the liver observed during hepatitis C in HIV-infected patients.
Methods:
A retrospective study of HIV-infected patients in whom a liver biopsy (LB) was performed for chronic hepatitis C or long-term pyrexia investigation. Hepatitis C Virus (HCV) status was determined by second generation ELISA testing. Data were reviewed from patients' charts. None of the patients had received acknowledged effective therapy for hepatitis C prior to LB. Presumed date of HCV contamination was that of first exposure to a risk factor.
Results:
The population consisted of 50 patients (74% male) with mean age 33 plus or minus 9 yrs; HIV contamination was through IV drug use in 78% of cases. Duration of VHC carriage was 8.4 plus or minus 2 yrs [range: 5-13]. Thirty one patients (62%) were at stage C3 according to CDC classification. Mean CD4 lymphocyte count was 213 plus or minus 328/mm3 [range: 1-1700], mean CD8 lymphocyte count was 500 plus or minus 382/mm3 [range: 35-1500]. Histological examination revealed cirrhosis in 7 cases (14%), chronic active hepatitis in 19 cases (39%), non-specific lobular hepatitis in 17 cases; LB was normal in 7 patients. Presence of chronic active hepatitis was associated with highest CD4 and CD8 lymphocyte count compared to non-progressive hepatitis: CD4 396 plus or minus 435 vs 104 plus or minus 165/mm3 (p=0.018), and CD8 754 plus or minus 423 vs 342 plus or minus 260/mm3 (p is less than 10-3) respectively. Presence of cirrhosis or chronic active hepatitis was not correlated to duration of viral hepatitis C disease.
Conclusions:
Histological lesions of the liver observed during the course of hepatitis C among HIV-infected patients depend on patient immune status, and are more severe when CD4 and CD8 lymphocyte sub-population counts are not deeply depressed.

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Nutritional status (NS) of HIV-infected patients.
Pugliese P; Pradier C; Carles M; Delpech D; Bernard E; Dellamonica P
Int Conf AIDS. 1994 Aug 7-12;10(2):223 (abstract no. PB0906).


OBJECTIVE:
to describe progression of HIV patients' NS according to their immunological status (IS)
METHODS:
descriptive cross-sectional survey on a stratified random sample. Stratification concerns IS determined by TCD4 count. GI: TCD4 < 50/mm3, GII: 50 < or = TCD4 < 150, GIII: 150 < or = TCD4 < 350, GIV: TCD4 or = 350/mm3. Assessment involves clinical condition, anthropometric and biological data, nutritional intake. Statistical tests: Epi-Info V5 software.
RESULTS:
42 patients included (mean age = 33+/-2.2 years). I.v. Drug Use = 28, homosexuality = 11, other = 3. TABULAR DATA, SEE ABSTRACT VOLUME. Difference is not significant for mineral elements (Phosphorus, Zinc, erythrocyte Magnesium). There appears an early alteration of anthropometric nutritional criteria (G III) as well as a reduction of daily Cal intake. Among the biological criteria studied, none allows a satisfactory assessment of NS.
CONCLUSIONS:
this early alteration pleads in favour of providing HIV patients with nutritional supplements before alteration of their IS. Adequate biological parameters remain to be determined.

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Development and installation of a computerized HIV medical file: the infectious diseases department experience in Nice, France.
Pugliese P; Pradier C; Huynh-Van E; Caissotti C; Berger J; Martini S; Pueyo B; Dellamonica P
Int Conf AIDS. 1996 Jul 7-12;11(1):149 (abstract no. Mo.C.1549).


Objectives:
To develop a computerised medical file in order to improve the quality of HIV patient management, facilitate communication between various staff members and create a useful data-base for research and evaluation of medical practices. The project is in progress within the Infectious Diseases Department in Nice, where 940 HIV patients are currently treated.
Methods
To ensure acceptability by the medical staff of changes linked with the installation of this software (rigour, standardisation.) the referees for the project (a physician, a secretary and a computer engineer) created a user-friendly model that was both compatible with existing data-bases and flexible (DB2/2 data-base management system; operating-and network management system: OS/2 V2.1 with CM2). The users (physicians, secretaries) modified this model which was subsequently installed in the care-units (nine servers). Improvements were added on site on the basis of initial user suggestions.
Results:
The system has been operating since June 1994 (421 patients, 823 entries). It ensures real-time data entry by hospital practitioners and dispatch of information via interfaces towards internal (infectious diseases department) and external (hospital and national) data-bases. It produces prescriptions and letters to the various persons concerned. Many functions facilitate patient management (decision AIDS, inclusion criteria for drug trials, drug interactions, stage classification.). Research projects based on collected data are in progress.
Conclusions:
The software is well accepted by the medical staff thanks to the strategy chosen for its implementation, its simple use and its multiple functions. Reliability of collected data provides the opportunity to use the information for research, and to evaluate medical practices with regard to recommendations concerning HIV patients management. Extension of the system to other units catering for HIV patients and use of this tool in other pathologies are contemplated.

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Natural killer cells at different clinical stages of human immunodeficiency virus infection: a one year prospective study of 163 patients.
Ticchioni M; Sapir J; Pugliese P; Durant J; Dellamonica P; Bernard A
Int Conf AIDS. 1993 Jun 6-11;9(1):226 (abstract no. PO-A24-0552).


OBJECTIVES: Deficiency in natural killer (NK) cells is observed in AIDS related disease and may be of prognostic relevance since NK cells are involved in protection against viral infection and tumor. Therefore, we investigated, in a one year prospective study, whether NK cells determination would be of pronostic relevance in the follow up of HIV infected-patients. METHODS: 163 patients (125 males, 38 females, 36 +/- 7 years old, stage CDC II/III: 14.7%, stage CDC IVc2, IVa: 44.17%, A.I.D.S: 44.1%) were included in the study. NK cells were determined by flow cytometry (FACScan, Becton-Dickinson) using CD3, CD16, CD56 mAb (Simulset, Becton-Dickinson).RESULTS: at baseline (M0), CD4 cells count/mm3 was 145 +/- 160 and NK cells/mm3 126 +/- 121 and at the end of the study (M12) 100 +/- 131and 101 +/- 84. No statistical correlation was observed between the relative decrease of NK cells (NK12-NK0/NK12) and survival. However, absolute NK cells number was correlated with the related decrease of CD4 cells counts (p < 0.003) implicating that a longer follow up is still necessary to evaluate prognostic value of NK cells in survival of HIV infected patients.

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Malaria attacks after returning from endemic areas:Failure or inadequate chemoprophylaxis?
Pugliese P, Martini-Wehrlen S, Roger PM, Fouche R, Pradier C, Carles M, Marty P, Fournier JP, Mousnier A, Dellamonica P
Presse Med 1997 Oct 4;26(29):1378-80

OBJECTIVE: Determine the causes of malaria attacks in subjects who have returned from endemic areas by assessing prescriptions for chemical prophylaxis and compliance.PATIENTS AND METHODS:All patients who developed a paroxysmal episode of malaria diagnosed at the University of Nice hospital in 1995 answered specific questions concerning their anti-malaria prophylaxis.RESULTS: Thirty-three patients were hospitalized for paroxysmal episodes of malaria in 1995. In 32 cases (97%) the attack resulted from either the lack of any prophylaxis (17 cases, 52%), inadequate prescription (11 cases, 12%) or poor compliance (4 cases, 12%). The prescribed chemical prophylaxis was not adapted to the chloroquinone-resistant area in 8 cases (24%) and medical recommendations concerning administration rules were inadequate in 3 cases (9%). Only one patient developed a paroxysmal episode despite correct compliance to a chloroquine-resistant zone-adapted well-conducted prescription. The cost of poor prophylaxis in terms of human suffering and financial cost was high for this preventable disease. Four patients had to be hospitalized in the intensive care unit and one died during hospitalization. The cumulative cost of hospitalization for these 33 cases was evaluated at 660,000 FF. CONCLUSION: Preventive measures for malaria must include better information for physicians on changing recommendations for chemical prophylaxis as well as better information for travelers provided by all those involved in organizing travel to endemic areas.

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