A review of the possible prognostic values of biochemical changes in patients with SARS-CoV-2 infections

Because of high mortality and long-term hospital stay among patients with SARS-CoV-2 infections, it is important to search for biochemical changes in different organs and systems that could be useful in diagnosis and prognosis of COVID-19. We conducted a literature search of online databases including PubMed, Web of Science, Scopus and Google scholar for relevant materials on biochemical changes in SARS-COV-2 infections published between December 2019 and March 2021. The review shows that SARS-COV-2 uses the angiotensin converting enzyme 2 (ACE2) for attachment and entry into host cells. These ACE2 are abundantly expressed by the epithelial cells of the respiratory tract and moderately expressed by the epithelial cells of the esophagus, stomach, duodenum, ileum, rectum, cholangiocytes, liver hepatocytes, pancreatic beta cells, and kidney tubular cells. This explains the systemic nature of SARS-COV-2 infection, and the high morbidity and mortality associated with COVID-19. Although, tests to assess biochemical changes are not specific enough for the diagnosis of SARS-CoV-2 infection, they may be useful for predicting outcome of COVID-19. This review highlights biochemical parameters that are significantly elevated or reduced in SARS-COV-2 infections, and which can be used as predictive factors of the severity and prognosis in COVID-19 patients.

Basic fibroblast growth factors as a biomarker of focal segmental glomerulosclerosis in HIV-positive and HIV-negative children

Background. HIV infection can lead to the development of HIV-associated nephropathy (HIVAN) with the majority of patients progressing to end-stage kidney disease. Previous studies have recognised basic fibroblast growth factor (bFGF) as a biomarker for HIVAN, since significant levels of bFGF low-affinity receptors have been found in the kidneys of HIV-infected children.Objective. To assess the association between bFGF and kidney disease in the development of focal segmental glomerulosclerosis (FSGS) in HIV-positive and negative children.Methods. The study group consisted of 31 children; HIVAN (n=11) and idiopathic FSGS (n=20). The control group consisted of both HIV-positive (n=20) and HIV-negative (n=20) children with no kidney disease. Serum samples from all patients in both the study and control groups were analysed for bFGF.Results. The concentration of bFGF was higher, in comparison with idiopathic FSGS children, in HIVAN children (p=0.0167). There was also a significant elevation of serum bFGF levels in children with HIVAN when compared with HIV-positive (p=0.0288) and HIV-negative (p=0.0043) control groups.Conclusion. This study demonstrated statistically significant differences between bFGF levels in children with HIVAN and a control group, although it failed to distinguish significant differences in bFGF levels between HIVAN and idiopathic FSGS children

Blood cellular markers of inflammation in Breast Cancer and response to Neoadjuvant Chemotherapy

Background:Breast cancer is the most common female malignancy in Nigeria. Neoadjuvant chemotherapy is the first line treatment for locally advanced breast cancer. The advancement of many cancers is accompanied by inflammation, and inflammatory cells play an essential role in the progression.Objective:To determine if haematological parameters can predict the responsiveness of breast cancer to neoadjuvant chemotherapy regime.Method:A prospective cohort study of all breast cancer patients who had neoadjuvant chemotherapy betweenJuly 2017 andDecember 2018was carried out. Haematological parameters of red cell count (RCC), white cell count(WCC), neutrophil count (NC), lymphocyte count (LC), platelet count (PC), red cell distribution width (RCDW), mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were measured. Response to chemotherapy was assessed by measuring the longest diameter of the lump and largest lymph node and applying the UICC criteria.Results: Thirty-five females with breast cancer with the age range of 33-82 years and mean age of 48± 11yearswere studied. The overall clinical response rate was 80% consisting of 40% complete clinical response, 40% partial clinical response, 8.6% stable disease and 11.4% progressive disease. Eleven (78.6%) with PLR values below average had good clinical response while 21.4% of those with PLR value above average had a good clinical response(χ2= 8.4, p =0.006)Conclusion: The study showed that PLR is associated with complete clinical response to neoadjuvant chemotherapy and should be used as part of routine assessment before chemotherapy

Biomarkers, shock index and modified early warning score among older medical hospital inpatients in Nigeria

Background: Biomarkers, shock index and modified early warning score (MEWS) are of public health importance because identification and prompt attention to them have been found to reduce mortality among older patients oadmission.Objectives: A study was undertaken to determine the biomarkers, shock index and MEWS that predict mortality on admission among older medical hospital inpatients.Methods: This was a prospective study of 450 patients (≥ 60 years) on the medical wards of University College Hospital, Ibadan.Biomarkers recommended by the National Institute on Aging such as blood pressure, heart rate and pulse rate (cardiovascular functioning); cholesterol and triglycerides (metabolic processes); T-cell counts (immune system status) and weight, body mass index and waist-to-hip ratio (indicators of obesity, chronic metabolic disorders and fat deposits) were assessed. Vital signs were recorded on admission and used to calculate the shock index and MEWS. Multivariate and survival analyses were carried out at p < 0.05.Results: Baseline temperature ≥ 39.0°c (p = 0.049), pulse rate ≥ 100 beats/minute (p = 0.034), systolic blood pressure (SBP) <120 mmHg (p = 0.048), shock index ≥1.0 (p = 0.041), age shock index (p = 0.032) and critical illness score (MEWS ≥5) p = 0.019 were significantly associated with mortality. Independent predictors of mortality on Cox regression analysis were temperature ≥ 39.0°C (HR = 3.317 [1.281­8.590]) and SBP < 120 mmHg (HR = 1.845 [1.025­3.322]).Conclusion: Prompt identification and management of fever and low blood pressure should improve the survival of older medical hospital inpatients

Statut des marqueurs du stress oxydatif au service de médecine interne et d'endocrinologie de l'hôpital du Mali

Introduction : Le stress oxydant est un déséquilibre entre les défenses antioxydantes endogènes etla production de molécules pro-oxydantes. L'objectif principal était d'étudier les différents marqueurs du stress oxydatif (oxydant et antioxydant) chez les sujets diabétiques et non diabétiques au niveau du service de médecine interne et d'endocrinologie de l'hôpital du Mali à Bamako. Matériels et méthodes : l'étude était transversale avec comparaison entre 30 sujets diabétiques et 30 sujets non diabétiques. Les marqueurs étudiés : Glutathion peroxydase érythrocytaire (GPX), la Superoxyde dismutase (SOD) intra érythrocytaire, l'acide urique plasmatique, Les bilirubines directes et totales, l'albumine ainsi que quelque marqueur de diagnostic et de suivi du diabète. Résultats. Trois pour cent de nos diabétiques avaient un taux de glutathion peroxydase élevé contre 9% des non diabétiques (p =0,005) ; augmentation de la Superoxyde dismutase des diabétiques 73,3% contre 40% des non diabétiques (p =0). Taux d'albumine, acide urique et la bilirubine identiques dans les deux populations ; hémoglobine glyquée était corrélée significativement aux complications dégénératives micro angiopathies (p=0,0058) et macro angiopathies (p=0,00017) chez les diabétiques. Conclusion : l'étude a montré une augmentation des défenses antioxydantes chez les trente diabétiques par l'élévation de la Superoxyde dismutase et normalisation relative du glutathion peroxydase

The integrated effect of moderate exercise on coronary heart disease

Background: Moderate exercise is associated with a lower risk for coronary heart disease (CHD). A suitable integrated model of the CHD pathogenetic pathways relevant to moderate exercise may help to elucidate this association. Such a model is currently not available in the literature.Methods: An integrated model of CHD was developed and used to investigate pathogenetic pathways of importance between exercise and CHD. Using biomarker relative-risk data, the pathogenetic effects are representable as measurable effects based on changes in biomarkers.Results: The integrated model provides insight into higherorder interactions underlying the associations between CHD and moderate exercise. A novel 'connection graph' was developed, which simplifies these interactions. It quantitatively illustrates the relationship between moderate exercise and various serological biomarkers of CHD. The connection graph of moderate exercise elucidates all the possible integrated actions through which risk reduction may occur.Conclusion: An integrated model of CHD provides a summary of the effects of moderate exercise on CHD. It also shows the importance of each CHD pathway that moderate exercise influences. The CHD risk-reducing effects of exercise appear to be primarily driven by decreased inflammation and altered metabolism

Taux de séroprévalence des marqueurs viraux (VIH/VHB/VHC) chez les donneurs du sang au Centre Provincial de Transfusion Sanguine de Matadi, Province du Kongo-Central

Contexte et objectif. La transmission des agents infectieux comme le virus de l?immunodéficience humaine (VIH), le virus de l?hépatite B (VHB) et le virus de l?hépatite C (VHC) représente une grande menace pour la sécurité transfusionnelle. L?objectif du présent travail était de déterminer le taux de séroprévalence des marqueurs des virus de l?immunodéficience humaine (VIH), de l?hépatite B (VHB) et de l?hépatite C (VHC) chez les donneurs du sang. Méthodes. Il s?agissait d?une étude documentaire basée sur le registre des donneurs du sang dans la période du 1erjanvier au 31 décembre 2016 au CPTS de Matadi (une ville portuaire) au Kongo- Central (RD Congo).Résultats : Les données des 95 donneurs du sang ont été analysées. Leur âge moyen était de 37,439,6 ans avec un sex ratio de 4 hommes pour 1 femme. Chez les 16 donneurs volontaires, le taux de séroprévalence était respectivement de 6,3% (VIH); 50% (AgHBs) et 31,3% (VHC). Pour les 61 familiaux, c?était 21,3% (VIH) ; 50,8% (AgHBs) et 26,2% (VHC). Et chez les 18 donneurs rémunérés : 22,2% (VIH); 61,1% (AgHBs) et 27,8% (VHC).Les co-infections ont été : VHB/C chez les donneurs volontaires (6,3%), VIH/VHB et VHB/C chez les familiaux (3,3% respectivement) et VIH/VHB et VHB/C chez les rémunérés (5,6% respectivement).Conclusion. Le taux de séroprévalence des marqueurs viraux (VIH/VHB/VHC) est élevé chez les donneurs du sang au CPTS de Matadi. Ces résultats sont liés soit à la séroprévalence desdits virus dans la communauté soit à une mauvaise sélection des donneurs du sang soit aux deux facteurs

Serious Bacterial Infections in Febrile Young Children: Lack of Value of Biomarkers

Background. Serious infections in children are difficult to determine from symptoms and signs alone. Fever is both a marker of insignificant viral infection; as well as more serious bacterial sepsis. Therefore; seeking markers of invasive disease; as well as culture positivity for organisms; has been a goal of paediatricians for many years. In addition; the avoidance of unnecessary antibiotics is important in this time of emerging multiresistant micro-organisms. Objective. To ascertain whether acute-phase reactant tests predict positive culture results.Methods. A prospective; cross-sectional study over a 1-year period included all documented febrile childre nunder the age of 5 years (with an axillary temperature =38oC) who presented to Steve Biko Academic Hospital; Pretoria; with signs and symptoms of pneumonia; meningitis and/or generalised sepsis. Every child had clinical signs; chest radiograph findings; urine culture; blood testing (full blood count; C-reactive protein; procalcitonin) and blood culture results recorded. Results. A total of 63 patients were enrolled; all of whom had an axillary temperature =38oC. C-reactive protein; procalcitonin and white cell count did not predict the presence of positive blood culture or cerebrospinal fluid culture results; nor infiltrates on chest radiographs. No statistically significant correlations were found between the duration of hospital stay and the degree of fever (p=0.123); white cell count (p=0.611); C-reactive protein (p=0.863) or procalcitonin (p=0.392). Conclusion. Biomarkers do not seem to predict severity of infection; source of infection; or duration of hospitalisation in children presenting to hospital with fever. The sample size is however too small to definitively confirm this viewpoint. This study suggests that clinical suspicion of serious infection and appropriate action are as valuable as extensive testing

Lactic Acidosis; Risk Factors and Predictive Laboratory Markers: a Nested Case Control Study in South Africa

Background: The incidence of antiretroviral therapy (ART)-induced lactic acidosis and its associated mortality may be reduced by appropriate dosing; risk stratification and early detection. Objectives: To describe the epidemiology of lactic acidosis; define the risk factors and identify predictive laboratory markers in the context of the roll-out of ART in South Africa. Design: A nested case control study. Risk factor analysis was adjusted for the established risk factors of weight and gender.Setting and subjects: Persons commenced on stavudine-containing therapy between 2004 and 2007 at Port Shepstone Hospital in KwaZulu-Natal were included. Persons with a body weight above 60 kg received Stavudine 40 mg twice daily; and those with a body weight below 60 kg; 30 mg twice daily.Outcome measures: Assessed risk factors included weight; gender; age; alanine transaminase (ALT); urea; creatinine; albumin; cholesterol; triglyceride (TG) levels; CD4 counts and viral loads.Results: Lactic acidosis occurred in 79 (17 per 1 000 person-years) of 1 762 people living with HIV on ART. Significant factors were being female [adjusted odds ratio (AOR) of 5.4] and increased body weight (adjusted OR of 1.1 per kg). The risk of lactic acidosis increased 6.6; 6.9 and 95 times (adjusted ORs) as weight increased from a baseline weight of 60 kg to 60-69 kg; 70-79 kg or 80 kg; respectively. Six months into therapy; predictors of developing lactic acidosis were an ALT 50 IU/l (adjusted OR of 11.1) and a higher TG (adjusted OR of 8.8 per mmol/l). No associations were found with regard to age; CD4 count; viral load; and creatinine or albumin levels.Conclusion: Obese females are at greatest risk of lactic acidosis; with an exponential increase in risk above 80 kg. The 30-mg dose may be preferable; given that a sharp increase in risk occurred at 60 kg; was most likely dose related; and that 30 mg has been shown to provide adequate virological suppression. Additional risk factors for lactic acidosis include a high ALT and TG levels at treatment

Classification moleculaire du cancer du sein au Maroc

La classification moleculaire des cancers du sein basee sur l'expression genique puis sur le profil proteique a permis de distinguer cinq groupes moleculaires: luminal A; luminal B; Her2/neu; basal-like et non-classees. L'objectif de cette etude realisee au CHU Hassan II de Fes est de classer 335 cancers du sein infiltrant en groupes moleculaires; puis de les correler avec les caracteristiques clinicopathologiques. Methodes Etude retrospective etalee sur 45 mois; comportant 335 patientes colligees au CHU pour le diagnostic et le suivi. Les tumeurs sont analysees histologiquement et classees apres une etude immunohistochimique en groupes: luminal A; luminal B; Her2+; basal-like et non-classees. Resultats 54.3 des tumeurs sont du groupe luminal A; 16des tumeurs sont du groupe luminal A; 16 luminal B; 11.3 Her2+; 11.3 basal-like et 7 non-classees. Le groupe luminal A renferme le plus faible taux de grade III; d'emboles vasculaires ainsi que de metastases ; alors que le groupe des non-classees et basal-like representent un taux eleve de grade III; une faible proportion d'emboles vasculaires et d'envahissement ganglionnaire. Ces facteurs sont significativement eleves dans les groupes luminal B et Her2+ avec un taux de survie globale de 78 et 76 respectivement. Dans le groupe luminal A; la survie globale des patientes est elevee (87) alors qu'elle n'est que de 49 dans le groupe des triples negatifs (basal-like et non-classes). Conclusion Le groupe luminal B est different du luminal A et il est de pronostic pejoratif vis a vis du groupe Her2+. Les caracteristiques clinicopatho- logiques concordent avec le profil moleculaire donc devraient etre pris en consideration comme facteurs pronostiques

Identification of Interaction Tests of Predictive Biomarkers in Cancer Clinical Trials

Predictive biomarkers are covariates that interact with treatment in relation to the outcome and thus; predictive biomarkers are characterized by interactions between the treatment and covariates. Many questions remain unanswered in this topic: What is the best design for detecting and validating a predictive biomarker? What can be the sample size required? What could be the statistical methods used to identify those interactions? The major problem of interaction tests is that they lack power; so that a very large trial would be required for the test to reach significance. The identification of a predictive factor becomes difficult if interactions of higher orders have to be investigated. We discussed the use of Martingale residuals combined with the classification and regression trees (CART) to identify which could be the optimal cut point in a continuous marker through data simulation. Our findings using these methods were very close to the expected results given the parameters of the simulation. Our conclusion is that the CART applied to Martingale residuals can be the good alternative of identifying predictive biomarkers. In practice we may need a cut point for a predictive biomarker so that we can know who among patients can benefit from the treatment and those who may be harmed by the treatment; especially when drugs are highly toxic

Monitorage de l'infection active a CMV par deux methodes : antigenemie PP65 et PCR qualitative sur plasma

Au cours de ce travail nous avons evalue deux methodes diagnostiques de l'infection active a CMV (antigenemie pp65 CMV et PCR qualitative) quant a leur utilite dans le monitorage de cette infection. Notre travail a porte sur 31 patients allogreffes de moelle osseuse dont 22 ont developpe une infection active a CMV. Le pourcentage des antigenemies positives etait de 59contre 28PCR positives. En mediane; les PCR se sont positivees 14 jours apres l'antigenemie. La duree de positivite de l'antigenemie etait de 5 semaines contre une semaine pour la PCR et la positivite de la PCR n'etait jamais isolee. Le taux de concordance de 61;5entre les deux techniques et le coefficient ( = 0.50) modere temoignerait d'un degre moyen de precision des resultats. La PCR sur plasma a presente une association plus importante avec la maladie a CMV (p= 0;014). La GVHD etait le seul facteur favorisant l'infection active a CMV (p=0;02). Cette derniere (p= 0;001) et la maladie a CMV (p= 0;04) ont presente des facteurs de mauvais pronostic chez nos patients. L'antigenemie constitue une methode de choix pour le diagnostic et le monitorage de l'infection active a CMV. Alors que la PCR qualitative sur plasma ne presente pas d'interet dans ce contexte

Les marqueurs sanguins dans la fibrose hepatique (A propos de 112 cas colliges au Centre Hospitalier Universitaire de Cocody)

INTRODUCTION: La Ponction Biopsie Hepatique (PBH) est un examen essentiel pour etablir le diagnostic; le pronostic et les indications therapeutiques de nombreuses maladies du foie. C'est aussi un examen invasif qui expose a des complications. C'est pourquoi des marqueurs biologiques sont proposes pour remplacer la PBH dans certaines indications. OBJECTIFS: Le but de notre travail est de determiner la relation entre des marqueurs seriques et un score anatomo pathologique de fibrose hepatique; d'etudier des marqueurs sanguins dans l'evolution de la fibrose hepatique. METHODOLOGIE:Cette etude retrospective s'est deroulee dans le service d'Hepato gastro enterologie du Centre Hospitalier Universitaire de Cocody. 112 dossiers de patients admis durant la periode de septembre 1998 en decembre 2004 ont ete inclus dans notre etude Les parametres etudies etaient: *Histologie: Relation Ponction Biopsie Hepatique avec classification Metavir des lesions histologiques associe au taux de prothrombine; taux des plaquettes; transaminases et au rapport ASAT/ALAT ; *Virologie: Dosage des Antigenes HBs et HBe; anticorps anti VHC ; *Biologie : Taux de prothrombine; plaquettes; transaminases; ASAT/ALAT. Les resultats sont les suivants: 50pour cent des patients avaient un TP compris entre 86-lOO'~/o. Le rapport ASAT/ALATl etait retrouve dans 46;7pour cent des cas. Il ressort de ce travail une hypertransaminasemie chez 2/3 des malades et 69pour cent des plaquettes sont abaissees. Conclusion : Notre etude montre que: 1. les transaminases sont augmentees pour un stade d'activite et fibrose 1 ; 2. le tata de Prothrombine n'est pas predictif de cirrhose ; 3. les plaquettes sont normales quel que soit le stade ; 4. le rapport ASAT/ALAT est predictif de cirrhose

Effects of Cassia occidentalis Aqueous Leaf Extract on Biochemical Markers of Tissue Damage in Rats

Purpose: Among the Hausas of Northern Nigeria; it is claimed by local (traditional) healers that the infusion of C. occidentalis leaves is used as a cure for hepatitis. This study was designed to evaluate the possible negative effects of the aqueous extract of this herb on serum total proteins; albumin; bilirubin; alanine amino transferase (ALT); aspartate amino transferase (AST) and alkaline phosphatase (ALP); as part of a larger study undertaken by these authors to ascertain the hepatoprotective potential of the plant extract. Methods: Fresh leaves of C. occidentalis were extracted with water and screened for phytochemical components. The extract was used for the treatment of 18 albino rats. Serum from these animals was used for the determination of the test parameters. Results: The extract showed hypoproteinaemic effect. ALT; AST and ALP levels were significantly elevated (P 0.05). Conclusion: Hypoproteinaemic effects; and increase in ALT; AST and ALP are indications that the crude extract of C. occidentalis leaves may be slightly toxic as a concoction for liver ailments

Determination des marqueurs de la lipoperoxydation par fluorimetrie et des vitamines antioxydantes par HPLC chez des africains residant a Bordeaux (France)

Le stress oxydant est le desequilibre entre le systeme antioxydant et le systeme radicalaire lie soit a une production excessive de radicaux libres soit a une diminution des moyens de leur degradation; entrainant ainsi des lesions biochimiques. Dans cette etude; nous nous sommes interesses a: - l'evaluation des taux plasmatiques moyens des marqueurs de la Lipoperoxydation (MDAL; MDAT et TBARS) et des vitamines Antioxydantes (vitamines A; E et B carotenes). - l'evaluation des taux moyens des vitamines antioxydantes dans les LDL.- la comparaison de tous les taux moyens a leurs valeurs usuelles d'une part; et la comparaison des taux moyens des vitamines antioxydantes dans le plasma ainsi que dans les LDL d'autre part. - une etude comparee entre les taux de TBARS des africains vivant en France et ceux vivant en cote d'Ivoire. - l'etude des correlations entre les marqueurs de la Lipoperoxydation et le sexe; l'age ainsi que les vitamines antioxydantes. Il ressort de celle etude les constats suivants: - le profil des marqueurs de la lipoperoxydation est plus eleve chez les africains vivant en France (2.08 nmol/ml) que celui de leurs compatriotes vivant en cote d'ivoire (1;12nmol/ml); d'ou l'apparition d'un stress oxydant. - l'apparition du stress oxydant est due soit a une augmentation des marqueurs de la lipoperoxydation (MDAL;MDAT et TBARS) soit a une diminution des piegeurs de radicaux libres (vitamines A; E et Beta carotenes).- le profil de la lipoperoxydation d'un individu depend de son age mais pas de son sexe

Markers in HIV Associated Tuberculosis in Kenya

Tuberculosis is one of the most frequent opportunistic infections in HIV-infected patients in developing countries. In some instances; manifestations of pulmonary tuberculosis precede all other HIV related signs and symptoms because of the high virulence of M. tuberculosis. In order to characterise the interaction between these two pathogens; clinical and immunological parameters in pulmonary tuberculosis patients with and without HIV infection were compared. Amongst newly diagnosed pulmonary tuberculosis patients the association of some of these changes with the clinical outcome were evaluated. Of these; 44were co-infected with HIV. Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone; P= 0.0292. Low CD4+ lymphocyte counts; lymphadenopathy and BCG scar absence could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients

A propos des marqueurs du VIH : marqueurs biologiques de suivi au cours de l'infection par le virus de l'immunodeficience humaine

"L'infection par le VIH evolue classiquement en trois phases : seroconversion; phase de latence clinique; apparition des signes cliniques de ""presida"" puis SIDA. entre l'etape du diagnostic serologique et la periode de la maladie ou sont utilisables les differentes classifications cliniques; peut donc exister une longue periode de latence clinique. Mais l'infection par le VIH est une maladie chronique et l'erosion du systeme immunitaire commence des la seroconversion et va se traduire par des anomalies biologiques. Ces anomalies seront autant de marqueurs utilisables pour determiner precocement le degre d'evolutivite de l'infection par le virus de l'immunodeficience humaine (VIH). De tels marqueurs sont indispensables pour la prise en charge des malades. Parmi ceux-ci quatre marqueurs biologiques independants; predictifs d'evolutions pejoratives a court terme (36 mois) peuvent etre utilises : deux marqueurs specifiques du VIH; l'antigenemie p24 et le titre en anticorps anti p24; deux marqueurs indirects non specifiques du VIH: la B2 microglobulinemie et le nombre absolu des lymphocytes CD4 circulants. En dehors de ces marqueurs biologiques classiques; de nombreux autres marqueurs ont ete evalues sans que leur interet pratique n'ait ete bien defini. Dans le futur les criteres biologiques previsionnels actuels seront certainement completes voire remplaces par l'evaluation virologique quantifiee de la charge virale"