A PROGRAM OF ACTION AND COOPERATION: Since 2001, a series of measures have been taken by the Memb... more A PROGRAM OF ACTION AND COOPERATION: Since 2001, a series of measures have been taken by the Member States, the European Union and the International authorities to reinforce the preparation and response to biological and chemical terrorist acts. It is essential that the Member States can mutually consult and coordinate their preparation and response as widely as possible. THE ROLE OF THE HEALTH SECURITY COMMITTEE: Together with the health security committee, the European Union has setup a mechanism of consultation and coordination that can be recommend and guide joint action in an emergency, and guarantee the coherence of the counter-actions throughout the Union. This is a committee also constitutes the framework within which the emergency strategies and model-simulations are exchange, and in which assistance in the form of expertise and other resources can be obtained among the Member States. IN THE YEARS TO COME: The future European Centre for the prevention and control of disease, the implantation and functioning of which will start in Sweden in 2005, will play a fundamental part in the harmonisation of the European response to any eventual terrorist acts, whether biological or chemical.
We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV encephalitis diagnosis. ... more We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV encephalitis diagnosis. 110 HIV-1 infected patients (mean age: 39 years; sex-ratio M/F: 94/16) were tested for HIV-1 RNA in plasma and CSF. Lumbar punctures were performed to explore cognitive deficit, seizure or fever. HIV encephalitis was diagnosed in 15 patients (14%), other CNS disease in 34 (31%), and fever without CNS disease in 61 (55%). HIV-1 RNA was detectable in 93% of the plasma and in 62% of the CSF. No significant difference was observed in CSF HIV-1 RNA between patients with or without HIV encephalitis. CSF HIV-1 RNA was correlated with plasma HIV-1 RNA (p < 0.01), CSF protein (p < 0.01) and CSF white cell counts (p < 0.01). The absence of any significant difference between patients with or without HIV encephalitis, suggests that the CSF HIV-1 RNA level is not a good marker for its diagnosis.
Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Am... more Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.
FREQUENT MUTATIONS: Associated with the high turnover rate of the HIV, frequent inverse transcrip... more FREQUENT MUTATIONS: Associated with the high turnover rate of the HIV, frequent inverse transcriptase errors lead to a wide range of possible mutations. Certain mutations can modify the response to antiretroviral agents. The development of resistant strains is mediated by the selection pressure of antiretroviral agents and occurs at a very variable rate depending on the antiretroviral agent used. TO LOWER THE RISK OF RESISTANCE: Persistent replication, whatever the cause, favors the emergence of resistant mutants. Thus the antiretroviral treatment must be initiated early and with the most powerful protocol possible in order to reduce viral replication as quickly as possible. CONTRIBUTION OF VIROLOGY TESTS: It is not always possible to predict the efficacy of antiviral agents from phenotyping and genotyping results. Their use is currently limited to cases of treatment failure. Their contribution in everyday clinical practice remains to be defined.
KAPOSI'S DISEASE: HHV-8 sequences have been found in all the epidemiological forms of Kap... more KAPOSI'S DISEASE: HHV-8 sequences have been found in all the epidemiological forms of Kaposi's disease. There is a direct relationship between HHV-8 infection and PBMC and later development of Kaposi's disease. The HHV-8 sequences can be found in spindle cells or endothelial cells in Kaposi lesions. OTHER DISEASES: HHV-8 is also associated with certain lymphomas including body-cavity-based lymphomas and Castleman's disease. It has also been put forward that there is a relationship between HHV-8 and multiple myeloma, epithelial tumors in kidney transplant recipients, angiosarcoma, and angiolymphoid hyperplasia.
A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the sma... more A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the smallpox virus represents a sufficiently high risk, which is difficult to manage and must be seriously taken into account. Two viral strains of the smallpox virus, which belong to the Poxviridae and orthopoxvirus-type families, are known. They are associated with various clinical presentations of smallpox, i.e., variola major and variola minor or "alastrim". Five clinical forms of varying prognosis are described. Common smallpox, haemorrhagic smallpox (the most severe form of the disease), mild smallpox (predominantly observed in vaccinated patients), flat-type smallpox (defined by coalescent and slowly progressive lesions) and so-called "sine eruptione" smallpox. This form is not as severe as variola major and the mortality rate is lesser. Smallpox must be systematically evoked on clinical elements and confirmed by electronic microscopy of a sample of liquid from a vesicle or pustule or a scab. The strains can be characterised by PCR (Polymerase Chain Reaction). It is symptomatic. Early vaccination, within 4 days following exposure to the virus, permits the reduction in mortality by 50%. The only efficient prevention is vaccination prior to any exposure to the virus. In the case of a bioterrorist attack, the United States and most of the EC countries propose to vaccinate only the health professionnals most exposed to the virus and those having contacted identified cases.
To describe the epidemiological characteristics of primary central nervous system lymphoma (PCNSL... more To describe the epidemiological characteristics of primary central nervous system lymphoma (PCNSL) and the evolution of the incidence of this lymphoma in HIV-infected patients with a more than 17-year follow-up. Eighty cases of PCNSL were analyzed from a data base of 2,263 AIDS subjects followed from 1983 to 1999 (3.5% of the patients with AIDS). At the time of diagnosis, PCNSL was the first AIDS defining event in 36% of the cases, median CD4 count was 9/mm3 (0-134); 82% of the patients were given antiretroviral therapy (HAART = 0). Only eight cases of PCNSL were observed after 1996 (median HIV RNA level: 250,000 copies/mL (24,000-1,500,000)). The incidence was 39 per 100 patients-year in 1991 and decreased to 1.9 in 1999. At the end of the study, 78 patients had died (98%). The median survival was one month before 1996 ([0-27], n = 72), and was ten months after ([0-44], n = 8). Two patients were still alive 38 and 44 months after diagnosis. After 1996, survival was increased in patients with good response to antiretroviral treatment and in patients with high CD4 count at the moment of diagnosis. After the introduction of HAART (1996), the incidence of PCNSL has decreased drastically and survival was increased.
A COMMON SITUATION: Among HIV-infected patients treated with antiretroviral regimens, 20% to 50% ... more A COMMON SITUATION: Among HIV-infected patients treated with antiretroviral regimens, 20% to 50% escape therapeutic control. The principal factors predictive of treatment failure are low CD4 counts and high viral load prior to institution of the antiretroviral treatment. Several virological and pharmacological mechanisms are implicated. Genotyping is particularly useful to optimize treatment in HIV-infected patients who escape therapeutic control, irrespective of the therapeutic strategy. A committee of experts has developed a scheme for adapting treatment to the very complex results of genotyping tests. The benefit of phenotyping remains to be established. Serum concentrations of antiretroviral agents should be determined and adapted in order to maximize the treatment effect. However, to manage therapeutic escape, the only method with a proven impact is genotyping. The possible usefulness of regular drug assays for adjusting treatment doses in case of therapeutic escape remains to be assessed in prospective trials.
A PROGRAM OF ACTION AND COOPERATION: Since 2001, a series of measures have been taken by the Memb... more A PROGRAM OF ACTION AND COOPERATION: Since 2001, a series of measures have been taken by the Member States, the European Union and the International authorities to reinforce the preparation and response to biological and chemical terrorist acts. It is essential that the Member States can mutually consult and coordinate their preparation and response as widely as possible. THE ROLE OF THE HEALTH SECURITY COMMITTEE: Together with the health security committee, the European Union has setup a mechanism of consultation and coordination that can be recommend and guide joint action in an emergency, and guarantee the coherence of the counter-actions throughout the Union. This is a committee also constitutes the framework within which the emergency strategies and model-simulations are exchange, and in which assistance in the form of expertise and other resources can be obtained among the Member States. IN THE YEARS TO COME: The future European Centre for the prevention and control of disease, the implantation and functioning of which will start in Sweden in 2005, will play a fundamental part in the harmonisation of the European response to any eventual terrorist acts, whether biological or chemical.
We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV encephalitis diagnosis. ... more We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV encephalitis diagnosis. 110 HIV-1 infected patients (mean age: 39 years; sex-ratio M/F: 94/16) were tested for HIV-1 RNA in plasma and CSF. Lumbar punctures were performed to explore cognitive deficit, seizure or fever. HIV encephalitis was diagnosed in 15 patients (14%), other CNS disease in 34 (31%), and fever without CNS disease in 61 (55%). HIV-1 RNA was detectable in 93% of the plasma and in 62% of the CSF. No significant difference was observed in CSF HIV-1 RNA between patients with or without HIV encephalitis. CSF HIV-1 RNA was correlated with plasma HIV-1 RNA (p < 0.01), CSF protein (p < 0.01) and CSF white cell counts (p < 0.01). The absence of any significant difference between patients with or without HIV encephalitis, suggests that the CSF HIV-1 RNA level is not a good marker for its diagnosis.
Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Am... more Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.
FREQUENT MUTATIONS: Associated with the high turnover rate of the HIV, frequent inverse transcrip... more FREQUENT MUTATIONS: Associated with the high turnover rate of the HIV, frequent inverse transcriptase errors lead to a wide range of possible mutations. Certain mutations can modify the response to antiretroviral agents. The development of resistant strains is mediated by the selection pressure of antiretroviral agents and occurs at a very variable rate depending on the antiretroviral agent used. TO LOWER THE RISK OF RESISTANCE: Persistent replication, whatever the cause, favors the emergence of resistant mutants. Thus the antiretroviral treatment must be initiated early and with the most powerful protocol possible in order to reduce viral replication as quickly as possible. CONTRIBUTION OF VIROLOGY TESTS: It is not always possible to predict the efficacy of antiviral agents from phenotyping and genotyping results. Their use is currently limited to cases of treatment failure. Their contribution in everyday clinical practice remains to be defined.
KAPOSI'S DISEASE: HHV-8 sequences have been found in all the epidemiological forms of Kap... more KAPOSI'S DISEASE: HHV-8 sequences have been found in all the epidemiological forms of Kaposi's disease. There is a direct relationship between HHV-8 infection and PBMC and later development of Kaposi's disease. The HHV-8 sequences can be found in spindle cells or endothelial cells in Kaposi lesions. OTHER DISEASES: HHV-8 is also associated with certain lymphomas including body-cavity-based lymphomas and Castleman's disease. It has also been put forward that there is a relationship between HHV-8 and multiple myeloma, epithelial tumors in kidney transplant recipients, angiosarcoma, and angiolymphoid hyperplasia.
A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the sma... more A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the smallpox virus represents a sufficiently high risk, which is difficult to manage and must be seriously taken into account. Two viral strains of the smallpox virus, which belong to the Poxviridae and orthopoxvirus-type families, are known. They are associated with various clinical presentations of smallpox, i.e., variola major and variola minor or "alastrim". Five clinical forms of varying prognosis are described. Common smallpox, haemorrhagic smallpox (the most severe form of the disease), mild smallpox (predominantly observed in vaccinated patients), flat-type smallpox (defined by coalescent and slowly progressive lesions) and so-called "sine eruptione" smallpox. This form is not as severe as variola major and the mortality rate is lesser. Smallpox must be systematically evoked on clinical elements and confirmed by electronic microscopy of a sample of liquid from a vesicle or pustule or a scab. The strains can be characterised by PCR (Polymerase Chain Reaction). It is symptomatic. Early vaccination, within 4 days following exposure to the virus, permits the reduction in mortality by 50%. The only efficient prevention is vaccination prior to any exposure to the virus. In the case of a bioterrorist attack, the United States and most of the EC countries propose to vaccinate only the health professionnals most exposed to the virus and those having contacted identified cases.
To describe the epidemiological characteristics of primary central nervous system lymphoma (PCNSL... more To describe the epidemiological characteristics of primary central nervous system lymphoma (PCNSL) and the evolution of the incidence of this lymphoma in HIV-infected patients with a more than 17-year follow-up. Eighty cases of PCNSL were analyzed from a data base of 2,263 AIDS subjects followed from 1983 to 1999 (3.5% of the patients with AIDS). At the time of diagnosis, PCNSL was the first AIDS defining event in 36% of the cases, median CD4 count was 9/mm3 (0-134); 82% of the patients were given antiretroviral therapy (HAART = 0). Only eight cases of PCNSL were observed after 1996 (median HIV RNA level: 250,000 copies/mL (24,000-1,500,000)). The incidence was 39 per 100 patients-year in 1991 and decreased to 1.9 in 1999. At the end of the study, 78 patients had died (98%). The median survival was one month before 1996 ([0-27], n = 72), and was ten months after ([0-44], n = 8). Two patients were still alive 38 and 44 months after diagnosis. After 1996, survival was increased in patients with good response to antiretroviral treatment and in patients with high CD4 count at the moment of diagnosis. After the introduction of HAART (1996), the incidence of PCNSL has decreased drastically and survival was increased.
A COMMON SITUATION: Among HIV-infected patients treated with antiretroviral regimens, 20% to 50% ... more A COMMON SITUATION: Among HIV-infected patients treated with antiretroviral regimens, 20% to 50% escape therapeutic control. The principal factors predictive of treatment failure are low CD4 counts and high viral load prior to institution of the antiretroviral treatment. Several virological and pharmacological mechanisms are implicated. Genotyping is particularly useful to optimize treatment in HIV-infected patients who escape therapeutic control, irrespective of the therapeutic strategy. A committee of experts has developed a scheme for adapting treatment to the very complex results of genotyping tests. The benefit of phenotyping remains to be established. Serum concentrations of antiretroviral agents should be determined and adapted in order to maximize the treatment effect. However, to manage therapeutic escape, the only method with a proven impact is genotyping. The possible usefulness of regular drug assays for adjusting treatment doses in case of therapeutic escape remains to be assessed in prospective trials.
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Papers by Philippe Bossi