Rhinoscleroma causing upper airway obstruction

Rhinoscleroma is a chronic granulomatous condition of the respiratory tract, and is not uncommon in tropical regions; particularly, Mexico, Central America and the Middle East. A few cases have been reported in North America, primarily involving immigrants from endemic countries. The causative organism is Klebsiella rhinoscleromatis, a Gram-negative coccobacillus. Diagnosis is made on the basis of culture of the organism and the characteristic pathology of Mikulicz cells on light microscopy. The condition primarily affects the upper airway, and frequently presents with nasal discharge, nasal obstruction or frontal facial pain. Despite the term 'rhinoscleroma', there may be involvement of the entire respiratory tract. Although the condition is slowly progressive, its natural course portends extensive destruction. Laryngotracheal involvement occurs in approximately 15% to 80% of cases, but patients rarely present with isolated laryngotracheal disease. In the present paper, a case of rhinoscleroma presenting with symptoms of upper airway obstruction is described. A 56-year-old male pharmacist, originally from Egypt, presented with a two-month history of shortness of breath on exertion. He complained of a foreign-body sensation in his throat with associated wheezing but denied chest pain, cough, hemoptysis or hoarseness. He had not experienced fever, weight loss or night sweats. His past medical history was significant for chronic sinusitis since childhood, characterized by long-standing malodourous secretions, crusting and intermittent nasal blockage. He had seen an otolaryngologist and received a tentative diagnosis of immotile cilia syndrome 12 years before his current presentation, although this diagnosis was not proven by biopsy and he was the natural father of two children. He had both hypertension and hyperlipidemia, and no known family history of respiratory illness or malignancy. He quit smoking six weeks before presentation and had a history of one pack/week for 20 years. On physical examination, he appeared well with no evidence of respiratory distress at rest. His blood pressure was 140/90 mmHg. His trachea was midline and he did not have cervical or supraclavicular adenopathy, cyanosis or clubbing. Examination of his chest revealed symmetric chest expansion with normal breath sounds throughout all lung fields, and specifically, an absence of stridor or wheezing. The remainder of his physical examination was normal. A chest x-ray taken at the time of presentation was normal, with no evidence of a mass or parenchymal disease. He had had an x-ray six years previously which appeared the same. He underwent spirometry and produced a flow-volume loop demonstrating classical features of fixed upper airway obstruction A computed tomography scan of the patient's thorax revealed normal lungs with wall thickening of the proximal trachea and an irregular-appearing endoluminal surface at the level of the thyroid. A subsequent computed tomography scan of the head and neck showed moderate circumferential narrowing of the subglottic larynx and superior trachea, as well as nodular thickening at the level of the inferior cricoid resulting in 50% to 60% endoluminal narrowing The patient underwent bronchoscopy, the findings of which were suggestive of a proximal tracheal tumour involving ©2005 Pulsus Group Inc. All rights reserved CASE REPORT the glottis and subglottis. The patient was referred to an otolaryngologist for evaluation of a potential malignancy. Laryngoscopy confirmed that there was a 3 cm tumour of the tracheal lumen, with evidence of cartilaginous destruction. The mid-and distal trachea were clear, as were the supraglottic and glottic larynx. Endoscopic resection was performed to improve the patient's airway and biopsies were sent for pathology. Pathology revealed a packed mucosal infiltrate of histiocytes admixed with inflammatory cells (mainly plasma cells). Silver methenamine and Gram staining revealed numerous Gram-negative bacilli within the histiocytes. The low-power view of the laryngeal biopsy showed an infiltrate of large, vacuolated histiocytes or Mikulicz cells Culture of the tumour specimen confirmed Klebsiella rhinoscleromatis was the causative organism. The patient was started on ciprofloxacin hydrochloride 500 mg twice a day for six weeks. He remained well after resection with no symptoms of upper airway obstruction. Bronchoscopic follow-up at six months demonstrated no recurrence of disease

Oxygen concentrators: a primary oxygen supply source

Equipment Oxygen concentrators: a primary oxygen supply source Purpose: Efforts to harmonize the standards of the CSA and the ISO, as they relate to compressed medical gas supply and piping, prompted us to review ten years experience with oxygen concentrators (OCs) in Canada used as a primary hospital oxygen supply. The goals of this study were; I) To document the number of Canadian OC Hospital sites, 2) to define what impact these units have had on medical practice and patient care, and 3) to explore trends in oxygen costing and utilization at the study sites. Methods: Following a four part mail survey and telephone follow up, site surveys were conducted for all hospitals utilizing an OC. Installation and service records, operating costs, amortization detail, leasing records as well as patient safety were all detailed. P-z~ts: Forty eight of 52 Canadian hospitals utilizing an OC participated. Clinical activity at the surveyed sites of 1996 included 30,642 surgical operations, 9,415 intensive care bed days and 364,529 emergency room visits. The cumulative survey represents 1,026,819 hr of OC operation. Dudng a 24 hr day, OCs operate 55 ---396 of the time. Financial analysis was validated at 43 of the 48 hospital sites. During the study the unit cost of oxygen was reduced by 62~ (P <.0001). An annual increase in oxygen consumption of I 1.5 -20% was documented (P <.0001). No patient care critical incidents related to OCs were reported. Conclusion: An OC installation which is CAN/CSA Z305.6-M92 compliant provides a safe, reliable, cost efficient primary hospital source of oxygen

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: Defining the role of gastroprotective agents

Treatment with anti-inflammatory drugs and the analgesic efficacy of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are compromised by a two-to fourfold increased risk of gastrointestinal complications. This increased risk has resulted in an increasing use of the new selective cyclooxygenase-2 inhibitors or coxibs, which, in clinical trials and outcomes studies, reduced gastrointestinal adverse events by 50% to 65% compared with conventional NSAIDs. However, the coxibs are not available to all patients who need them, and NSAIDs are still widely used. Moreover, treatment with a coxib cannot heal preexisting gastrointestinal lesions, and cotherapy with an antisecretory drug or mucosal protective agent may be required. This paper addresses the management of patients with risk factors for gastrointestinal complications who are taking NSAIDs and makes recommendations for the appropriate use of 'gastroproteccontinued on next pag

Evaluation of asthma control by physicians and patients: Comparison with current guidelines

BACKGROUND: Current asthma consensus guidelines recommend a series of criteria for determining whether asthma is controlled. It is not known whether physicians are using these criteria to assess treatment needs and how effective such assessments are compared with patient assessment of asthma control. OBJECTIVE: To compare the parameters used by physicians and patients with asthma to determine whether asthma control is acceptable, according to the current Canadian asthma consensus guidelines. DATA AND METHODS: A total of 183 Canadian physicians, mostly general practitioners, evaluated 856 patients with mildly to moderately uncontrolled asthma who were not using anti-inflammatory medications at the time of entry in the study. Physician characteristics and patient demographics were obtained. The physicians completed two questionnaires, one assessing the level of asthma control of the patient on an ordinal scale from 1 (very poor) to 5 (very good) and another indicating the parameters that were used to evaluate this level of control. Patients answered an asthma control questionnaire identical to the one completed by the physician and completed a six-question asthma control questionnaire, with each question scored on a 0-to 6-point scale. RESULTS: Although according to current asthma guidelines all patients surveyed had uncontrolled asthma, 66.2% of patients and 43.3% of physicians rated control of asthma symptoms as adequate to very good. The average scores for patient-and physician-rated asthma control were 3.0±0.2 and 2.6±0.2, respectively. The average patient score on the Juniper asthma questionnaire was 12.2±6.3. Physicians used a mean of seven parameters to assess the patient's level of asthma control, mostly beta 2 -agonist need, followed by cough, wheezing, shortness of breath, limitation of physical activities and night-time awakenings. Pediatricians used cough more frequently as an evaluation parameter, and respirologists measured pulmonary function more often than other physcians. Some parameters not usually included in guideline criteria for control, such as fatigue, need to clear throat, colored sputum, headache and dizziness, were sometimes used by physicians. Only 10% and 18% of physicians used measurements of forced expiratory volume in 1 s and peak expiratory flow, respectively, in asthma control assessments. CONCLUSIONS: The present study shows that the selection of asthma control criteria among physicians varies and is not always in keeping with current asthma guidelines. Both patients and physicians often consider asthma to be controlled, when according to current guidelines, it is not, and patients consider their asthma better controlled than do physicians. Objective measures of airflow obstruction are rarely used to assess asthma control. The present study stresses the need for improved disseminationto both patients and physicians -of current recommendations on how asthma control should be determined. Key Words: Asthma control; Asthma treatment; Physicians' assessment Résumé à la page suivante Évaluation de la maîtrise de l'asthme par les médecins et les patients : Comparaison avec les directives actuelles HISTORIQUE : Les directives consensuelles actuelles sur l'asthme pré-conisent l'application d'une série de critères pour déterminer si l'asthme est maîtrisé. On ignore si les médecins utilisent ces critères pour évaluer les besoins thérapeutiques et on ignore quelle est l'efficacité de ces évalu-ations comparativement à l'évaluation que les patients peuvent faire de la maîtrise de leur asthme. OBJECTIF : Comparer les paramètres utilisés par les médecins et les patients asthmatiques pour déterminer si la maîtrise de l'asthme est acceptable selon les directives consensuelles canadiennes sur l'asthme. DONNÉES ET MÉTHODES : En tout, 183 médecins canadiens, la plupart généralistes, ont évalué 856 patients présentant un asthme légèrement à modérément non contrôlé qui n'utilisaient pas d'anti-inflammatoires au moment de leur admission à l'étude. Les caractéristiques des médecins et les données démographiques des patients ont été obtenues. Les médecins ont répondu à deux questionnaires, l'un évalu-ant le degré de maîtrise de l'asthme du patient sur une échelle de 1 (très faible) à 5 (très bonne) et un autre indiquant les paramètres utilisés pour évaluer ce degré de maîtrise. Les patients ont répondu à un questionnaire sur la maîtrise de leur asthme identique à celui qui a été soumis aux médecins et ils ont répondu à un questionnaire de six questions sur la maîtrise de l'asthme, chaque réponse étant reportée sur l'échelle en six points. RÉSULTATS : Bien que selon les directives actuelles en matière d'asthme tous les patients interrogés présentaient un asthme non maîtrisé, 66,2 % des patients et 43,3 % des médecins ont déclaré que les symptômes d'asthme étaient soit adéquatement soit très bien contrôlés. Les scores moyens quant à la maîtrise de l'asthme selon l'évaluation des patients et des médecins ont été de 3,0 ± 0,2 et de 2,6 ± 0,2, respectivement. Le score moyen des patients au questionnaire Juniper sur l'asthme a été de 12,2 ± 6,3. Les médecins ont utilisé en moyenne sept paramètres pour évaluer le degré de maîtrise de l'asthme de leurs patients, principalement le recours aux bêta 2 -agonistes suivi de la toux, des sillements, de l'essoufflement, de la restriction des activités physiques et des réveils nocturnes. Les pédiatres ont utilisé la toux plus souvent comme paramètre d'évaluation et les pneumologues ont mesuré la fonction pulmonaire plus souvent que les autres médecins. Certains paramètres généralement exclus des critères de maîtrise préconisés par les directives, comme la fatigue, les raclements de gorge, les expectorations colorées, la céphalée et les étourdissements, ont parfois été utilisés par les médecins. Seulement 10 % et 18 % des médecins ont utilisé des mesures de VEMS et débit expiratoire de pointe, respectivement, dans leurs évaluations de la maîtrise de l'asthme. CONCLUSION : La présente étude montre que les médecins adoptent différents critères pour mesurer la maîtrise de l'asthme et que ces critères ne concordent pas toujours avec les directives actuelles. Les patients et les médecins considèrent souvent que l'asthme est maîtrisé alors que selon les directives actuelles, il ne l'est pas et les patients considèrent leur asthme mieux maîtrisé que leur médecin. Les mesures objectives d'obstruction bronchique sont rarement utilisées pour évaluer la maîtrise de l'asthme. La présente étude rappelle la nécessité de mieux faire connaître aux médecins et aux patients les recommandations actuelles sur la façon dont on doit mesurer le degré de maîtrise de l'asthme. I t is recommended that asthma treatment be based on the patient's degree of asthma control, and the current asthma consensus guidelines recommend a series of criteria to be used to determine whether asthma is adequately controlled (1,2). These criteria usually include the minimal use of short-acting beta 2 -agonists, minimal or no respiratory symptoms, and the ability to conduct normal daily activities, in addition to optimal pulmonary function. Physicians do not always know practice guidelines, and the guidelines' recommendations are only partially followed (3,4). Although the asthma guidelines only guide practice, some general principles about how to assess asthma control and the need for objective measures of airflow obstruction are important recommendations. However, in their daily practices, physicians use mostly subjective measures to assess asthma control. We do not know, however, whether the criteria suggested by the current guidelines are used regularly in practice and whether a given physician's assessment of asthma control is consistent with that of the patient with asthma. The present study looked at adult and pediatric patients diagnosed with mild to moderate asthma. Its objectives were: to identify the parameters used by physicians in determining asthma control; to compare patient's perception of asthma control with the findings of a validated asthma control questionnaire; to compare physician's and patient's perceptions of asthma control; and to compare those results with recommendations of the 1999 Canadian Asthma Consensus Report on asthma control assessment (1). DATA AND METHODS Patient recruitment and study design The present analysis used baseline data from a noncontrolled, observational, open-label study on changes in asthma control following the introduction of montelukast sodium in patients with uncontrolled asthma who were not using anti-inflammatory medications. Two hundred thirtytwo physicians were asked to recruit prospectively five patients, six years of age and older, with a diagnosis of mild to moderate asthma. Physicians were recruited consecutively from a list of potential investigators. Patients could be enrolled in the program if they were currently using a beta 2 -agonist on demand more than three and less than 15 times a week (eight to 28 inhalations); if they required inhaled corticosteroid therapy but could not or would not use this type of therapy (1); and if, in the treating physician's clinical judgment, they would benefit from leukotriene antagonist therapy. The severity of asthma could be considered mild to moderate according to current criteria (1). After obtaining informed consent, the treating physician and the patient independently completed their asthma questionnaires. Questionnaires The information collected on the questionnaire given to physicians consisted of physician identification and specialty, along with the baseline demographics of the patient: age, sex, race, number of years since the first diagnosis of asthma and status of prior asthma therapy. The physician assessed the patient's level of asthma control on an ordinal scale from 1 (very poor) to 5 (very good). Treating physicians were also asked to indicate, from a list of 20 parameters, the ones that they used to assess each patient's level of asthma control. The choices consisted of 18 asthma-related symptoms and two pulmonary function tests, forced expiratory volume in one second (FEV 1 ) and peak expiratory flow (PEF). The information collected at baseline from the patient came from a six-question asthma control questionnaire developed by Juniper et al (5), where each question was scored on a 0 to 6 scale (better to worse). Using a validated questionnaire provided another means of assessing asthma control. Patients also assessed asthma control on an ordinal scale from 1 (very poor) to 5 (very good). The patients were asked: "How would you rate the control of your asthma symptoms (on a five point scale from very good to very poor)?". For children, parents were asked to answer the questionnaires and assess control. Data collected for each patient were faxed, after each visit, to Symbios RP Inc (Montreal, Quebec) that was responsible for data collection. Data analysis Descriptive statistics were calculated on all data collected during the program. This included verifying data for consistency with expected ranges of all variables, and descriptive statistics (such as means, medians, ranges, standard deviations and percentages) obtained with regard to the identification of the asthma control parameters used by physicians, the number of times that each physician answered yes to each symptom and the rankings of the 20 symptoms (from most commonly used to least commonly used), according to the physician specialty (pediatrician, general practitioner, and community allergist/respirologist). Data were also analyzed by level of asthma control, as assessed by the physician (five categories); level of asthma control, as assessed by the patient (five categories); total asthma symptom score by the patient; and patient age group by either adult (age 15 or older) or child (age 14 or under). The 95% CIs were calculated wherever warranted. For comparison of the patient's perception of asthma control in relation to the Juniper asthma control questionnaire, the overall score for each patient was calculated as the sum of the scores for each question. Because each question was scored from 0 to 6, the maximum possible score was 36 and the minimum was 0. The mean ± SD and percentage of patients with each possible score value were calculated, along with a Spearman's correlation coefficient of this score with the patient's overall control rating (scored from 1 to 5). A similar correlation coefficient was calculated for the physician's overall rating of the patient's control. For comparison of the physician's and patient's perceptions of asthma control, the proportion of the patients reporting each category of control (from 1 [very good] to 5 [very poor]) was compared with the same measurement from the physicians. A paired difference (patient-physician) of the control category was created, where the categories were numbered 1 through 5, and the average difference and average absolute difference were reported with 95% CIs (the average of the patient-physician scores). The average absolute difference was the absolute difference between the scores of the two groups, irrespective of the direction of the change. Tests for patient-physician differences were carried out. A five by five cross-tabulated table was created displaying all possible results for patients and physicians, where the diagonal elements represent agreement and the off-diagonal elements represent disagreement between the patients and physicians. Overall analyses were performed, combining data from all patients, and separate analyses for pediatric and adult cases were performed. RESULTS Physician and patient baseline enrolment data A total of 183 physicians of 232 initially recruited (78.9%) evaluated 856 patients between April and December 1999. Patient status data are shown in The sample of 183 recruiting physicians consisted of 73.8% general practitioners, 14.2% allergists and respirologists, and 12.0% pediatricians; the three groups enrolled 74.6%, 11.7% and 13.7%, respectively, of the patients in the study. As expected, the great majority of patients recruited by pediatricians were children (94.5%), whereas general practitioners, and allergists and respirologists had a 4:1 adult to child age distribution recruitment ratio. General practitioners recruited 85.8% of all adults and 47% of all children; allergists and respirologists, 13.2% and 8%, respectively; and pediatricians, 1% and 45%, respectively. Identification of the asthma control parameters used by physicians Recruiting physicians reported using approximately seven parameters to assess their patients' level of asthma control throughout the study. Compared with other physician specialties, pediatricians used cough more frequently as an asthma evaluation parameter, while community allergists and respirologists used cough less frequently than primary care physicians. Overall, objective measures of airflow obstruction were rarely used to assess asthma control, with FEV 1 being obtained at the office for only 10% of patients and PEF for only 18%. Community allergists and respirologists used FEV 1 and PEF significantly more often than primary care practitioners (in 61% and 48% of patients, respectively). Comparison of the patient's perception of asthma control in relation to an asthma-control questionnaire The control of asthma symptoms was rated as very poor or poor by 33.8% of patients and 56.7% of physicians; as adequate by 38.2% of patients and 28.6% of physicians; and as good by 21% of patients and 12.2% of physician

Is there anything left to learn? A report on the Fifth International Workshop on HIV Drug Resistance

Although insight into the viral dynamics of human immunodeficiency virus (HIV) infection has increased dramatically over the past year, there remains much to learn in the field of antiretroviral drug resistance. Transmission of isolates with primary drug resistance is increasingly recognized. With respect to reverse transcriptase inhibitors, it appears that the use of drugs in combination may forestall the development of resistance once therapy has been initiated. Further, certain findings, particularly with respect to zidovudine and lamivudine, suggest that emergence of resistance to one agent may lead to increased susceptibility to another. These data may allow evaluation of innovative treatment strategies to avoid the development of multidrug resistance, which has now been reported in a number of settings. Protease inhibitors (PIs) are, on an individual basis, the most potent antiretroviral compounds available today. A number of studies have shown that resistance to these agents develops after the accumulation of several mutations in the protease gene of HIV. As with reverse transcriptase inhibitors, the use of PIs in the context of regimens designed to suppress viral replication as much as possible appears to forestall, perhaps indefinitely, the development of drug resistance. Although different patterns of resistance mutations have been described for the different PIs available, the issue of cross-resistance remains unresolved. For the time being, it may be best to consider all PIs as a single agent that must always be used in a regimen designed to maximally suppress viral load. In conclusion, research in the field of antiretroviral drug resistance has never been more active and productive. It is hoped that such research will lead to the development of an integrated model of the clinical and laboratory management of HIV-infected individuals. Key Words: Antiretroviral therapy, Drug resistance, Human immunodeficiency virus Nous reste-t-il quelque chose à apprendre ? Un rapport sur le cinquième Atelier international sur la pharmacorésistance du VIH RÉSUMÉ : Bien que la compréhension de la dynamique virale de l'infection au virus de l'immunodéficience humaine ait considérablement évolué au cours de la dernière année, de nombreuses lacunes restent à combler dans le domaine de la pharmacorésistance aux agents antirétroviraux. La transmission d'isolats présentant une pharmacorésistance primaire est de plus en plus reconnue. En ce qui concerne les inhibiteurs de la transcriptase inverse, il semble que l'utilisation d'une combinaison de médicaments peut prévenir le développement d'une résistance une fois que le traitement a débuté. De plus, certains résultats, en particulier ceux concernant la zidovudine et la lamivudine, permettent de croire que l'émergence d'une résistance à un médicament peut entraîner une augmentation de la sensibilité à un autre agent. Ces données pourraient O ver the past two years, researchers have become aware that the phase of clinical latency of human immunodeficiency virus (HIV) infection is not accompanied by an arrest of viral turnover. In fact, over 10 10 new virions are produced every day (1). These data have been further refined, using mathematical models that show that the half-life of plasma virions is 6 h and the average HIV generation time (from release of a virion from a cell in the circulation to its subsequent release from the next cell it infects) is just over two days (2). Given these dynamics, it is not surprising that plasma viral load decreases very rapidly once appropriate antiretroviral therapy is initiated. This is particularly true if highly effective antiretroviral drug combinations are used, whether these include protease inhibitors (PIs) (3) or non-nucleoside reverse transcriptase inhibitors NNRTIs (4). In many cases, viral load is suppressed to such an extent that the possibility of eventual eradication of HIV from the body is being suggested (5). It has now clearly been shown that the risk of long term disease progression is directly related to the baseline plasma viral load, even in patients with high CD4 cell counts at the time of their initial evaluation (6). It has also been shown that treatment-induced changes in plasma RNA levels, taken together with CD4 cell counts, are valid predictors of the clinical progression of HIV-related disease (7). Analysis of the large American AIDS Clinical Trials Group (ACTG) 175 trial suggests that, as a single marker, baseline viral load may be the most relevant predictor of ultimate response to nucleoside analogue therapy (8). Further, the magnitude of decrease in viral load is the best predictor of the clinical efficacy of the antiretroviral agents. With all of this information in mind, it has been suggested that plasma HIV RNA levels be used routinely in clinical practice (9). It is widely held that this approach would improve the care of the HIV-infected patient. ANTIRETROVIRAL RESISTANCE Resistance of clinical HIV isolates to antiretroviral compounds was first described in 1989 (10). A number of studies have suggested that drug resistance is of clinical relevance (11,12) and needs to be considered in any complete virological model of HIV disease. Since 1992, a group of international researchers has met every year to consider the issue and significance of drug resistance. The 1996 meeting, held in conjunction with the XIth International Conference on AIDS, was particularly timely, in light of the renewed emphasis on the use of clinical laboratory measures for individual patient management. As the meeting progressed, it became apparent that, although insight into the significance of viral load has increased dramatically over the past years, there remains much to learn in the field of antiretroviral drug resistance. REVERSE TRANSCRIPTASE INHIBITORS Large American and European trials, which have allowed researchers to appreciate the clinical significance of plasma viral load levels, have also allowed researchers to evaluate the potential significance of antiretroviral drug resistance, most notably to zidovudine (ZDV). At the meeting, reports of both the Delta (Europe/Australia) and ACTG 175 (USA) studies were presented. In both studies, patients received one or more of ZDV, didanosine (ddI) or zalcitabine (ddC). Interestingly, resistance to ddI and ddC was uncommon, even in patients on long term therapy. Of 220 Delta study patients, only 10 were found to have ZDV-resistant isolates (carrying previously described mutations at codons 70 and/or 215 of the reverse transcriptase gene). More complete clinical correlation was established in a group of 89 patients enrolled in ACTG 175. After 56 weeks on ZDV, patients with drug-resistant isolates had experienced a median decline in CD4 counts of 100 cells/µL and an increase in viral load of 0.5 log 10 copies/mL plasma. Patients with wild type isolates had a rise of 17 cells/µL and a decline of 0.4 log 10 copies/mL. Although the differences between the groups are relatively unimpressive, they do suggest clinical consequences of drug resistance. In this context, the possibility of transmission of strains with primary drug resistance is of some concern. In a Swiss cohort of primary HIV infection, nine of 124 patients were found to carry such strains resistant to ZDV. A similar proportion was reported in a Dutch cohort (four of 35), with three of four having been transmitted in the previous year. In Canada, a cross-sectional study of 91 infected children failed to reveal the existence of similar strains, but active ongoing surveillance is required to monitor trends in this field. Beginning in 1995, the combination of ZDV and lamivudine (3TC) has been widely used in clinical practice. In early studies of 3TC monotherapy, resistance was found to emerge quite readily. Data on the emergence of drug resistance in long term ZDV/3TC combination therapy are now available. NUCA 3001 was a controlled, randomized multicentre study of ZDV versus 3TC versus ZDV/3TC in previously untreated patients. ZDV resistance mutations were identified in eight of 12 paCan J Infect Dis Vol 9 No 3 May/June 1998 173 Report on the Fifth International Workshop of HIV Drug Resistance permettre d'évaluer des stratégies de traitement innovatrices pour éviter le développement d'une multirésistance médicamenteuse, désormais signalée dans un certain nombre d'endroits. Les inhibiteurs de la protéase sont, actuellement, sur une base individuelle, les composés antirétroviraux les plus puissants. Plusieurs études ont démontré que la résistance à ces agents survient après l'accumulation de plusieurs mutations dans le gène de la protéase du VIH. Pareil aux inhibiteurs de la transcriptase inverse, l'utilisation des inhibiteurs de la protéase, dans le cadre de régimes conçus pour supprimer au maximum la réplication virale, semble prévenir, peut-être indéfiniment, l'apparition d'une pharmacorésistance. Bien que différents schémas de mutations causant une résistance aient été décrits concernant les différents inhibiteurs de la protéase actuels, la question d'une résistance croisée reste sans réponse. Actuellement, il est préférable d'envisager tous les inhibiteurs de la protéase qui sont disponibles comme agent unique devant toujours être utilisé dans un régime visant à supprimer au maximum la charge virale. En conclusion, les recherches dans le domaine de la pharmacorésistance aux antirétroviraux n'ont jamais été aussi actives et productives. On espère que de telles recherches conduiront à la mise au point d'un modèle intégré de la prise en charge clinique et en laboratoire des individus infectés par le VIH