RESUMO
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos.
Assuntos
Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ácido Ascórbico/uso terapêutico , Avaliação da Tecnologia Biomédica , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Vacina BCG/uso terapêutico , Colchicina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Interferon gama/uso terapêutico , Corticosteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Ritonavir/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lopinavir/uso terapêutico , Interferon alfa-2/uso terapêutico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêuticoRESUMO
Patient-derived xenografts are a useful tool in cancer immunology, as they allow researchers to study human cancers in vivo when starting with a relatively small amount of human tumor tissue. These models make it possible to study tumor cell-intrinsic changes that occur in response to external stimuli including cytokines like interferon gamma (IFNγ) that are important for effective anti-tumor immune responses. IFNγ responsiveness can be measured by assessing surface expression of MHC class I on tumor cells, the molecule on which tumor antigens are presented to cytotoxic T cells in the tumor microenvironment. Low levels of MHC class I and lack of responsiveness have been associated with resistance to T-cell directed therapies like immune checkpoint inhibitors. In this chapter, we present a protocol for an assay to screen patient-derived xenografts for their responsiveness to IFNγ. The results of this assay can be used as a starting point for uncovering cancer cell-intrinsic mechanisms of resistance to immunotherapies in patient tumors.
Assuntos
Testes Imunológicos de Citotoxicidade/métodos , Imunoterapia , Interferon gama/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Neoplasias/terapia , Animais , Antígenos de Neoplasias , Linhagem Celular Tumoral , Humanos , Interferon gama/farmacologia , Ativação Linfocitária/imunologia , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Interpretação Estatística de Dados , Indústria Farmacêutica/ética , Fraude/ética , Ensaios Clínicos como Assunto/ética , Indústria Farmacêutica/normas , Indústria Farmacêutica/tendências , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Interferon gama/uso terapêutico , Proteínas Recombinantes/uso terapêuticoRESUMO
Semiparametric transformation models provide a very general framework for studying the effects of (possibly time-dependent) covariates on survival time and recurrent event times. Assessing the adequacy of these models is an important task because model misspecification affects the validity of inference and the accuracy of prediction. In this paper, we introduce appropriate time-dependent residuals for these models and consider the cumulative sums of the residuals. Under the assumed model, the cumulative sum processes converge weakly to zero-mean Gaussian processes whose distributions can be approximated through Monte Carlo simulation. These results enable one to assess, both graphically and numerically, how unusual the observed residual patterns are in reference to their null distributions. The residual patterns can also be used to determine the nature of model misspecification. Extensive simulation studies demonstrate that the proposed methods perform well in practical situations. Three medical studies are provided for illustrations.
Assuntos
Modelos Estatísticos , Bioestatística , Quimioterapia Adjuvante , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Doença Granulomatosa Crônica/tratamento farmacológico , Humanos , Interferon gama/uso terapêutico , Método de Monte Carlo , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
The hypereosinophilic syndromes continue to challenge our clinical acumen and skills. Prednisone, hydroxyurea, and interferon alpha 2b are three of the oldest agents that allow control of eosinophilia and its devastating clinical consequences. They still work. As our experience with them has grown, it has become evident that use of these agents in combination will control eosinophilia in most patients. Moreover, with time, the doses can frequently be reduced. Even with the advent of newer agents for treatment of hypereosinophilic syndromes, these three medications still afford an excellent, cost-effective avenue for disease management.
Assuntos
Hidroxiureia/uso terapêutico , Síndrome Hipereosinofílica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Prednisona/uso terapêutico , Receptores de Glucocorticoides/metabolismo , Apoptose , Humanos , Hidroxiureia/economia , Síndrome Hipereosinofílica/economia , Síndrome Hipereosinofílica/fisiopatologia , Interferon-alfa/economia , Interferon gama/uso terapêutico , Prednisona/economiaRESUMO
The different manifestations of Candida albicans infection are dictated by an underlying defect in the immune response of the host. Protective immunity to disseminated candidiasis, the manifestation of C. albicans infection discussed in this review, has traditionally been ascribed to innate immunity with emphasis on the role of granulocytes. Lately, however, immunological studies have learned that host defence against disseminated candidiasis is based on a complex interplay between innate and cell-mediated immunity. Despite the availability of new antifungal agents, mortality associated with disseminated C. albicans infection remains high. Immunotherapy that augments host defence is an important strategic option in the battle against disseminated candidiasis. Here, the authors review the chronological events in the pathogenesis of disseminated candidiasis that aid in predicting the impact of existing immunotherapy and the development of future immunomodulating strategies.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antifúngicos/uso terapêutico , Candida albicans , Candidíase/tratamento farmacológico , Adjuvantes Imunológicos/economia , Animais , Candida albicans/imunologia , Candidíase/imunologia , Candidíase/prevenção & controle , Proteínas do Sistema Complemento/imunologia , Células Dendríticas/imunologia , Quimioterapia Combinada , Fluconazol/uso terapêutico , Vacinas Fúngicas/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Interferon gama/uso terapêutico , Células Matadoras Naturais/imunologia , Fagócitos/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Receptores de Reconhecimento de Padrão/imunologia , Proteínas Recombinantes , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Human immunodeficiency virus type 1 (HIV-1) infection results in different patterns of viral replication in pediatric compared to adult populations. The role of early HIV-1-specific responses in viral control has not been well defined, because most studies of HIV-1-infected infants have been retrospective or cross-sectional. We evaluated the association between HIV-1-specific gamma interferon (IFN-gamma) release from the cells of infants of 1 to 3 months of age and peak viral loads and mortality in the first year of life among 61 Kenyan HIV-1-infected infants. At 1 month, responses were detected in 7/12 (58%) and 6/21 (29%) of infants infected in utero and peripartum, respectively (P = 0.09), and in approximately 50% of infants thereafter. Peaks of HIV-specific spot-forming units (SFU) increased significantly with age in all infants, from 251/10(6) peripheral blood mononuclear cells (PBMC) at 1 month of age to 501/10(6) PBMC at 12 months of age (P = 0.03), although when limited to infants who survived to 1 year, the increase in peak HIV-specific SFU was no longer significant (P = 0.18). Over the first year of life, infants with IFN-gamma responses at 1 month had peak plasma viral loads, rates of decline of viral load, and mortality risk similar to those of infants who lacked responses at 1 month. The strength and breadth of IFN-gamma responses at 1 month were not significantly associated with viral containment or mortality. These results suggest that, in contrast to HIV-1-infected adults, in whom strong cytotoxic T lymphocyte responses in primary infection are associated with reductions in viremia, HIV-1-infected neonates generate HIV-1-specific CD8+-T-cell responses early in life that are not clearly associated with improved clinical outcomes.
Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Interferon gama/uso terapêutico , Sequência de Aminoácidos , Antivirais/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/mortalidade , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Quênia , Fragmentos de Peptídeos/química , Gravidez , Complicações Infecciosas na Gravidez/virologia , Carga ViralRESUMO
Protein Design Labs is developing fontolizumab, a humanized anti-interferon gamma monoclonal antibody, for the potential treatment of autoimmune diseases. By February 2003, the company was actively seeking to outlicense the development and commercialization rights to fontolizumab outside of the US and Canada.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Interferon gama/antagonistas & inibidores , Interferon gama/uso terapêutico , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais Humanizados , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Desenho de Fármacos , Indústria Farmacêutica/organização & administração , Humanos , Interferon gama/químicaRESUMO
In medical studies, we commonly encounter multiple events data such as recurrent infection or attack times in patients suffering from a given disease. A number of statistical procedures for the analysis of such data use the Cox proportional hazards model, modified to include a random effect term called frailty which summarizes the dependence of recurrent times within a subject. These unobserved random frailty effects capture subject effects that are not explained by the known covariates. They are typically modelled constant over time and are assumed to be independently and identically distributed across subjects. However, in some situations, the subject-specific random frailty may change over time in the same manner as time-dependent covariate effects. This paper presents a time-dependent frailty model for recurrent failure time data in the Bayesian context and estimates it using a Markov chain Monte Carlo method. Our approach is illustrated by a data set relating to patients with chronic granulomatous disease and it is compared to the constant frailty model using the deviance information criterion.
Assuntos
Teorema de Bayes , Biometria , Doença Granulomatosa Crônica/tratamento farmacológico , Humanos , Interferon gama/uso terapêutico , Cadeias de Markov , Modelos Estatísticos , Método de Monte Carlo , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Proteínas RecombinantesRESUMO
In this paper, the author argues that the requirement to conduct randomised clinical trials to inform policy in cases where one wants to identify a cheaper alternative to known effective but expensive interventions raises an important ethical issue. This situation will eventually arise whenever there are resource constraints, and a policy decision has been made not to fund an intervention on cost effectiveness grounds. It has been thought that this is an issue only in extremely resource poor settings. This paper gives an example from the United Kingdom illustrating that this is also a problem faced by richer countries.
Assuntos
Ética em Pesquisa , Medicina Baseada em Evidências/ética , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Grupos Controle , Análise Custo-Benefício/ética , Atenção à Saúde/economia , Atenção à Saúde/ética , Alocação de Recursos para a Atenção à Saúde/ética , Alocação de Recursos para a Atenção à Saúde/métodos , Humanos , Interferon gama/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Organizações de Normalização Profissional/ética , Qualidade de Vida , Projetos de Pesquisa/normas , Medicina Estatal/economia , Medicina Estatal/ética , Reino UnidoRESUMO
Visceral leishmaniasis (VL) is a severe disease associated with infection of the reticuloendothelial system by Leishmania species. The infection is acquired through sandfly bites. Recent large scale epidemics of VL in east Africa and India and the emergence of a HIV epidemic make VL a priority for the World Health Organization. Pentavalent antimonials have been cornerstone of treatment for the last six decades. The appearance of antimonial-resistance and the development of lipid formulations of amphotericin B have changed the pattern of VL treatment. Within the past five years, miltefosine has been demonstrated as the first effective and safe oral treatment against VL. The price of miltefosine is yet to be determined. However, miltefosine will certainly be cheaper than lipid formulations of amphotericin B, which are beyond the financial capacity of the poor countries. Because it can be administered orally, miltefosine is suited for the treatment of large number of patients who get affected during epidemics, particularly in regions where the parasites are resistant to the currently used agents. Here, we recommend different treatment schedules according to the resistance pattern and the region-specific socio-economical and cultural factors.
Assuntos
Antiprotozoários/uso terapêutico , Leishmania/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Animais , Antiprotozoários/economia , Antivirais/economia , Antivirais/uso terapêutico , Resistência a Medicamentos , Infecções por HIV/complicações , Humanos , Interferon gama/economia , Interferon gama/uso terapêutico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/epidemiologiaAssuntos
Aprovação de Drogas/legislação & jurisprudência , Indústria Farmacêutica/economia , Interferon gama/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Biotecnologia , Ensaios Clínicos Fase III como Assunto , Custos de Medicamentos , Indústria Farmacêutica/legislação & jurisprudência , Humanos , Interferon gama/economia , Investimentos em Saúde , Proteínas Recombinantes , Estados Unidos , United States Food and Drug AdministrationRESUMO
Randomized clinical trial designs commonly include one or more planned interim analyses. At these times an external monitoring committee reviews the accumulated data and determines whether it is scientifically and ethically appropriate for the study to continue. With failure-time endpoints, it is common to schedule analyses at the times of occurrence of specified landmark events, such as the 50th event, the 100th event, and so on. Because interim analyses can impose considerable logistical burdens, it is worthwhile predicting their timing as accurately as possible. We describe two model-based methods for making such predictions during the course of a trial. First, we obtain a point prediction by extrapolating the cumulative mortality into the future and selecting the date when the expected number of deaths is equal to the landmark number. Second, we use a Bayesian simulation scheme to generate a predictive distribution of milestone times; prediction intervals are quantiles of this distribution. We illustrate our method with an analysis of data from a trial of immunotherapy in the treatment of chronic granulomatous disease.
Assuntos
Modelos Biológicos , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Teorema de Bayes , Simulação por Computador , Doença Granulomatosa Crônica/tratamento farmacológico , Doença Granulomatosa Crônica/imunologia , Humanos , Imunoterapia , Interferon gama/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/mortalidade , Fatores de TempoRESUMO
In this paper we propose formulae for calculating the expected number of events or, alternatively, the required trial duration, for clinical trials involving two treatment groups in which patients may potentially experience multiple events and the data will be analysed using a multiplicative intensity (MI) model. We use a partial likelihood-based approach and examine in detail two MI models: one that includes a binary treatment variable as the only covariate and a three-state Markov process model in which a binary time-varying covariate is added to the previous model. For the simpler model, our formula coincides with those derived by Cook using full likelihood methods. We present applications of the derived formulae to chronic granulomatous disease and breast cancer data sets.
Assuntos
Modelos Biológicos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Criança , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Fluoximesterona/uso terapêutico , Doença Granulomatosa Crônica/tratamento farmacológico , Humanos , Interferon gama/uso terapêutico , Funções Verossimilhança , Cadeias de Markov , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Tamanho da Amostra , Tamoxifeno/uso terapêuticoRESUMO
A 20-year-old patient suffering from chronic granulomatous disease developed pulmonary aspergillosis with thoracic wall invasion. Treatment with itraconazole combined with 3-weekly injections of interferon gamma (INF gamma) improved the patient's general state of health within two months. Functional signs resolved totally and x-ray images continued to improve for 6 months. INF gamma was withdrawn after 11 months and was replaced with cotrimoxasole. Itraconazole was continued in a long-term regimen. Four years after onset of treatment, the clinical status of the patient remained satisfactory, and the radiological aspect was unchanged. Pulmonary aspergillosis affects up to 40% of patients suffering from chronic granulomatous disease. Mortality is high, to the order of 25%. The classical treatment is based on amphotericin B, but this case points out the significant contribution of itraconazole as first-line therapy. This antimycotic has been suggested for prophylaxis. The combined use of INF gamma can be discussed due to the uncertainties about its long-term effects and because of the requirement for 3-weekly injections. High cost is another important consideration.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/etiologia , Granuloma/complicações , Interferon gama/uso terapêutico , Itraconazol/uso terapêutico , Pneumopatias Fúngicas/etiologia , Sepse/complicações , Adulto , Aspergilose/tratamento farmacológico , Aspergilose/patologia , Doença Crônica , Análise Custo-Benefício , Custos de Medicamentos , Granuloma/microbiologia , Humanos , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/patologia , Masculino , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: Several clinical studies have focused on the therapeutic effects of interferon gamma (IFN-gamma) in patients with severe atopic dermatitis (AD), although the dosage of recombinant IFN-gamma (rIFN-gamma), therapeutic schedule, and the degree of clinical improvement were different among studies. Although the exact mechanism of action of IFN-gamma therapy in AD is not clear, the beneficial effects of IFN-gamma have been attributed mainly to an immunomodulating effect on the expression of certain immunologic markers. OBJECTIVE: Our purpose was to study the therapeutic effect of two different dosages of rIFN-gamma on AD and to investigate the change of lesional expression of infiltrating inflammatory cell markers associated with rIFN-gamma therapeutic efficacy. METHODS: Fifty-one patients with severe recalcitrant AD were treated with rIFN-gamma. Twenty patients were treated with 0.5 x 10(6) IU/m(2) of rIFN-gamma (low-dose [LD] group); 21 patients received 1.5 x 10(6) IU/m(2) of rIFN-gamma (high-dose [HD] group); and 10 patients received placebo. The patients were injected subcutaneously 3 times a week for 12 weeks. Immunohistochemical study was performed in 20 patients of the HD group in the initial visit and after completion of rIFN-gamma therapy with a panel of 14 monoclonal antibodies as markers of inflammatory cells and cytokines. RESULTS: The disease severity of the 2 groups treated with rIFN-gamma was reduced significantly at the end of treatment compared with that of the placebo group (P<.05). More rapid clinical improvement and more effective treatment outcome were seen in the HD group than in the LD group for the initial 6-week treatment period; however, the clinical improvement in both of the treated groups was stable and maintained after week 8 of treatment. Immunohistochemical findings showed statistically significant reduction in the lesional expression of CD25 and EG2 cells that infiltrated into skin after rIFN-gamma therapy. CONCLUSION: This study demonstrated that rIFN-gamma therapy for AD is safe and effective. In the early phase of therapy, a higher dosage of rIFN-gamma is more effective; and for the maintenance of clinical improvement, a lower dosage of rIFN-gamma is recommended when high cost and effectiveness of rIFN-gamma are considered. The therapeutic efficacy of rIFN-gamma in AD might be in part related to the decreased number of CD25(+) and EG2(+) inflammatory cells infiltrated into skin.
Assuntos
Antineoplásicos/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Interferon gama/uso terapêutico , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Biomarcadores/análise , Análise Custo-Benefício , Citocinas/análise , Dermatite Atópica/imunologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Imuno-Histoquímica , Interferon gama/administração & dosagem , Linfócitos/imunologia , Masculino , Receptores de Interleucina-2/análise , Resultado do TratamentoRESUMO
CORRESPONDENCE TO: Professor J P Galmiche, Hépato-Gastroentérologie, Hôtel Dieu, CHU de Nantes, 44035 Nantes Cedex, France (email: galmiche@easynet.fr). This consensus conference followed the rules developed by the French Agence Nationale pour le Développement de l'Evaluation Médicale (ANDEM). Briefly, this required an organising committee, a working group whose task was to make a comprehensive critical review of the literature before the conference was held, a panel of experts, and a jury. The conference was held over two days and included (a) a public session with presentations by experts working in areas relevant to the consensus questions, (b) questions and statements from conference attendees, and (c) deliberation by the jury, followed by the drafting of conclusions and recommendations. (GUT 1998;:892-898)
Assuntos
Hepatite C/prevenção & controle , Programas de Rastreamento , Doença Crônica , França , Hepatite C/diagnóstico , Hepatite C/terapia , Humanos , Interferon gama/uso terapêutico , Programas de Rastreamento/economia , Fatores de RiscoRESUMO
A number of novel biologic agents are being introduced to replace, enhance, or modulate immune responses in medical illnesses. The use of these therapies has become crucial in treating some of these diseases, yet there is relatively little available information about their cost-effectiveness. Two examples are presented. Interferon gamma, used in chronic granulomatous disease, costs about $140 for a 100-microg vial; yearly costs average $21840 per patient. Study data estimated a 69% to 76% reduction in serious illness with interferon gamma treatment; a reduced incidence of infections could cover drug costs. Intravenous immunoglobulin is used lifelong in antibody deficiency and clearly reduces the number of serious illnesses. Projected savings derive from fewer hospital admissions and reduced organ damage, but infusion costs vary widely because of the prices charged for the drug and infusion services.
Assuntos
Doenças do Sistema Imunitário/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Adjuvantes Imunológicos/economia , Adjuvantes Imunológicos/uso terapêutico , Custos e Análise de Custo , Custos de Cuidados de Saúde , Humanos , Doenças do Sistema Imunitário/economia , Imunoglobulinas Intravenosas/economia , Imunoglobulinas Intravenosas/uso terapêutico , Interferon gama/economia , Interferon gama/uso terapêutico , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Estados UnidosRESUMO
The most frequent bacterial infections in patients infected with HIV and suffering from AIDS are non-tuberculous mycobacterial infections. Their incidence is increasing all the more as the survival of profoundly immunocompromised patients is prolonged. There are unknown factors as regards the precise origin of these infections and as to the exact epidemiology of atypical mycobacteria. It is known that 95 per cent of atypical mycobacterial infections are due to M. avium. If the pathophysiology of the infection (involving the intervention of cytokines and also factors in relation to the virulence of the germ) is imperfectly understood, the atypical mycobacteria are an independent cause of mortality in advanced stages of the disease. The clinical picture is that of a low grade fever with weight loss and a deterioration in the general physical state. There are subtle physical signs such as a fall in the functional capacity accompanied by weight loss and an unexplained anaemia these should also suggest a diagnosis. More rarely the infection will be localised. The clinical diagnosis will be confirmed by bacteriology which has been aided by recent progress in molecular biology. With the arrival of the newer macrolides it has been shown that treatment prolongs survival in a significant manner. Current recommendations consist of a treatment with a combined regime including a minimum of Clarithyromycin and Ethambutol. The place for polychemotherapy remains to be determined in particular the role for Rifabutine and Amikacine. Immunomodulation by interferon-gamma or GCSF are also under review. The duration of treatment and the necessity of long term suppressive treatment is the object of randomised studies. Prophylaxis is currently recommended for patients with CD4 < 75/mm3. The role of Rifabutine and the new macrolides remains to be determined. Finally, in a large European study the objective is to compare prophylaxis to systematic bacteriological surveillance both as regards efficacy, tolerance, and in terms of pharmaco-economics.