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Au décours d'un épisode aigu de COVID-19 symptomatique, plus de 30 % des patients adultes ont encore des symptômes à 1-2 mois et 10 à 15 % à 6-8 mois. Il peut s'agir de symptômes persistants ou de nouveaux symptômes. Si les plus fréquents sont une fatigue sévère, une dyspnée et des signes neurocognitifs, de nombreux autres organes peuvent être atteints. Ces symptômes évoluent en général de façon fluctuante et sont souvent majorés par l'effort physique ou intellectuel. Avec le temps, ils évoluent de façon lente vers l'amélioration. L'absence de documentation virologique de l’épisode aïgu (la PCR n'ayant pu être faite et/ou la sérologie étant négative) n'exclut pas ce diagnostic. L'origine de ces symptômes n'est pas encore élucidée et certaines hypothèses sont en cours d'exploration, comme par exemple une persistance virale qui a été démontrée dans certains cas, une réponse inflammatoire notamment mastocytaire excessive, ou bien un défaut de l'immunité innée ou adaptative. Des facteurs génétiques et hormonaux sont possiblement associés. La prise en charge des patients doit être initiée dès le premier recours aux soins. Suite à une analyse approfondie des symptômes, des diagnostics seront portés et feront l'objet d'une prise en charge multidisciplinaire où les traitements symptomatiques et la rééducation tiennent une place importante. Si le recours à l'hospitalisation est rare, ces formes prolongées, maintenant appelées « COVID long », vont avoir un impact sociétal majeur nécessitant la mise en place de politiques publiques adaptées.

Background Hereditary angioedema (HAE) is associated with a heavy burden of illness. Objective To evaluate use of lanadelumab in a French Authorization for Temporary Use (ATU) program. Methods ATU requests were made between October 12, 2018, and March 13, 2019; patients were followed through September 23, 2019. At entry, patients received lanadelumab 300 mg every 2 weeks. HAE attack characteristics were evaluated at day (D) 0 and months (M) 3 and 6. Patients completed the Angioedema Quality of Life (AE-QoL) questionnaire at initiation and monthly and the Angioedema Activity Score questionnaire daily in 28 day cycles (AAS28). Results In total, 77 patients received ≥ 1 lanadelumab dose; 69 had ≥ 1 quarterly follow-up visit (analyzed population). Mean (standard deviation [SD]) lanadelumab exposure was 240.4 (53.7) days. Lanadelumab dose was modified in 12 patients (mostly to every 4 weeks). For the analyzed population, compared with attacks/month (mean [SD]) within 6 months before ATU (2.68 [2.54]), fewer attacks occurred between initiation and first visit (0.16 [0.42]; P Conclusions Lanadelumab reduced attack rates, improved quality of life, and was generally well tolerated.

International audience; Objective: Hereditary angiœdema (HAE) is a rare autosomal dominant disease characterized by recurrent, unpredictable, potentially life-threatening swelling. Objective is to assess the management of the acute HAE attacks in the real life setting through a call center in France.Methods: A pre-specified ancillary study of SOS-HAE, a cluster-randomized prospective multicenter trial, was conducted. HAE patients were recruited from 8 participating reference centers. The outcome of interest was the rate of hospitalization.Results: onerhundred patients were included. The median (quartile) age was 38 (29-53) years, and 66 (66%) were female. Eighty (80%) patients had HAE type I, 8 (8%) had HAE type II and 12 (12%) patients had FXII-HAE. Fifty-one (51%) patients had experienced at least one time the call center during the follow-up. Nine over 166 (5%) attacks for 9 different patients resulted in hospital admission to the hospital (in the short-stay unit, ie

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures.OBJECTIVE: To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS).METHODS: The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before being diagnosed as having C1-INH-HAE.RESULTS: In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients with family members diagnosed as having C1-INH-HAE were significantly less likely to be misdiagnosed than patients without a family history (140 of 366 [41.7%] vs 38 of 58 [65.5%], respectively; P = .001). Patients with a prior misdiagnosis had longer median delay to C1-INH-HAE diagnosis (13.3 years) than patients without (1.7 years; P < .001).CONCLUSION: From this large database, approximately 50% of patients with C1-INH-HAE type I or II have previously had their conditions misdiagnosed, most commonly as allergic angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct diagnosis, during which time patients cannot access effective, lifesaving treatment.TRIAL REGISTRATION: ClinicalTrials.gov: NCT01034969.

International audience; STUDY OBJECTIVE: Hereditary angioedema is a rare disease associated with unpredictable, recurrent attacks of potentially life-threatening edema. Management of severe attacks is currently suboptimal because emergency medical teams are often unaware of new specific treatments. The objective of this trial is to test whether a dedicated national telephone care-management strategy would reduce resource use during severe hereditary angioedema attacks.METHODS: We conducted a cluster-randomized multicenter prospective trial of patients with a documented diagnosis of hereditary angioedema (type I, II or FXII hereditary angioedema). Participants were enrolled between March 2013 and June 2014 at 8 participating reference centers. The randomized units were the reference centers (clusters). Patients in the intervention arm were given a national free telephone number to call in the event of a severe attack. Emergency physicians in the SOS-hereditary angiœdema (SOS-HAE) call center were trained to advise or prescribe specific treatments. The primary outcome was number of admissions for angioedema attacks. Economic evaluation was also performed.RESULTS: We included 100 patients in the SOS-HAE group and 100 in the control group. During the 2 years, there were 2,368 hereditary angioedema attacks among 169 patients (85%). Mean number of hospital admissions per patient in the 2-year period was significantly greater in the usual-practice group (mean 0.16 [range 0 to 2] versus 0.03 [range 0 to 1]); patient risk difference was significant: -0.13 (95% confidence interval -0.22 to -0.04; P=.02). Probabilistic sensitivity graphic analysis indicated a trend toward increased quality-adjusted life-years in the SOS-HAE group.CONCLUSION: A national dedicated call center for management of severe hereditary angioedema attacks is associated with a decrease in hospital admissions and may be cost-effective if facilities and staff are available to deliver the intervention alongside existing services.

Objectives The objective of this study was to analyse the respective roles of personal factors and HIV infection markers on the systemic immune activation/inflammatory profile of long-term antiretroviral treatment-controlled patients. Patients and methods A panel of soluble immune activation/inflammatory biomarkers was measured in 352 HIV-infected treatment-controlled patients from the APROCO-COPILOTE cohort, all of whom were started on a PI in 1997–99 and had a final evaluation 11 years later, and in 59 healthy controls. Results A total of 81.5% of the patients were male, with the following characteristics: median age 49 years; 620 CD4 cells/mm3; 756 CD8 cells/mm3; CD4/CD8 ratio 0.81; BMI 23.0 kg/m2; waist-to-hip ratio 0.95. Markers of inflammation—high-sensitivity (hs) IL-6 (median and IQR) (1.3 pg/L, 0.7–2.6), hs C-reactive protein (CRP) (2.1 mg/L, 0.9–4.5) and D-dimer (252 ng/mL, 177–374)—were elevated compared with healthy controls (P Conclusions In these long-term treatment-controlled HIV-infected patients, all systemic markers of inflammation and immune activation were increased compared with healthy controls. This was related to demographic and behavioural factors, but not to markers of severity of the HIV infection. Intervention to decrease low-grade inflammation must thus prioritize modifiable personal factors.

Despite the availability of guidelines for the specific treatment of hereditary angioedema (HAE) attacks, HAE morbidity and mortality rates remain substantial. HAE attacks are a major medical issue requiring specific treatment as well as a considerable socio-economic burden. We report a protocol designed to test whether a dedicated call centre is more effective than usual practice in the management of patients experiencing an HAE attack. This prospective, cluster-randomised, single-blind, parallel-group, multicentre trial evaluates the morbidity and consequent socio-economic costs of the management of patients experiencing an HAE attack by a dedicated call centre as compared to usual practice. The trial aims to recruit 200 patients. Patients in the intervention arm are provided with an SOS-HAE card with the call centre’s freephone number that they can access in the case of an attack. The centre’s mission is to provide recommended expert advice on early home treatment. The centre can route the call to a local emergency medical service with competency in HAE management or even arrange for the drugs needed for the specific treatment of an HAE attack to be sent to the emergency department of the local hospital. The primary outcome measure is the number of hospital admissions for an HAE attack. Each patient will be followed up every 2 months for 2 years. The study has been approved by the ethics committee (Comite de Protection des Personnes d’Ile de France 10; registration number: 2012-A00044-39; date of approval: 19 January 2012). The SOS-HAE protocol has been designed to address the handling of attacks experienced by patients with HAE in the home. The proposed trial will determine whether the setting up of a dedicated call centre is more effective than usual practice in terms of reducing morbidity as given by the numbers of hospital admissions. The results are also anticipated to have important implications in terms of socio-economic costs for both healthcare services and patients. ClinicalTrials.gov NCT01679912 .

Background: Buprenorphine was approved in France for treating opiate dependence in July 1995 and can be prescribed by general practitioners (GPs). Most studies assessing buprenorphine maintenance treatment (BMT) outcomes have taken place in GP settings. An evaluation of BMT outcomes in patients already followed for their HIV-infection could supply additional information about the changes in addictive practices in a non-GP setting. Methods: We assessed BMT discontinuations and the course of self-reported addictive behaviours and characteristics associated with buprenorphine-injection misuse in 114 HIV-infected patients on BMT who were followed in a hospital-based outpatient department. Results: The continuous series of follow-up visits at which these 114 patients reported regular buprenorphine prescriptions accounted for 237.5 person-years of observation, i.e. 475 follow-up visits. Of the 114 patients on BMT, 43% continued BMT throughout the follow-up, 40% stopped it, and results for 17% were not available either because they did not answer the self-administered questionnaire (5%) or because they were lost to follow-up (12%). Addictive behaviours declined but buprenorphine injection misuse remained stable. Depression measured by the CESD score (RR=1.04 95%CI [1.01–1.06]), cocaine use (RR=2.48 95%CI [1.31–4.68]) and alcohol consumption exceeding 4 alcohol units (AU) per day (RR=2.29, 95%CI [1.17–4.46]) were independently associated with buprenorphine injection misuse among stabilised BMT patients. Conclusions: Despite the reduction in drug injection after starting BMT, buprenorphine injection misuse mainly involves patients with characteristics of severe addiction. Better monitoring of the illicit drug use patterns of patients on BMT may suggest new medical strategies for GPs to improve BMT outcomes.

In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.

To assess the effect of zidovudine on productive HIV infection of the brain.To correlate the incidence of HIV-specific neuropathology with zidovudine therapy.We examined 192 AIDS cases neuropathologically; 97 had never been treated with zidovudine, 72 had received zidovudine for over 3 months and until death, 23 had their treatment terminated more than 1 month before death.The incidence of HIV encephalitis/HIV leukoencephalopathy (HIVE/HIVL) and of multinucleated giant cells (MGC) was significantly lower in patients who had received zidovudine than in those who had never received zidovudine. The yearly incidence of HIVE/HIVL increased between 1982 and 1987 probably because of improved survival, and decreased between 1987 and 1990 although the percentage of patients treated with zidovudine increased. Since 1991 the incidence of HIVE/HIVL and of MGC increased slightly. The percentage of patients treated with zidovudine until death decreased and that of patients whose treatment was terminated increased concomitantly. In 1989 and 1990, most patients whose treatment was terminated had MGC and HIVE/HIVL. In 1991 and 1992 this incidence decreased markedly, coinciding with the introduction of dideoxyinosine therapy.Zidovudine treatment significantly reduces the occurrence of productive HIV infection of the brain in AIDS. Discontinuing zidovudine therapy may favour the occurrence of HIV encephalitis. Substitution therapy with dideoxyinosine also appears to protect against HIV-specific brain pathology.

Objective. To delineate the different types of inflammatory vascular diseases (IVD) occurring in patients with human immunodeficiency virus (HIV) infection. Methods. Muscle, nerve, or skin biopsy specimens from 148 symptomatic HIV-infected individuals were reviewed, and subgroups of vasculitis were identified using the American College of Rheumatology (ACR) 1990 clinicopathologic criteria for the classification of vasculitis. Results. IVD was documented in 34 patients (23%) and included necrotizing arteritis (3 patients), non-necrotizing arteritis (1 patient), neutrophilic IVD (7 patients), mononuclear IVD (17 patients), and other small vessel inflammatory changes (6 patients). According to the ACR criteria, 11 patients could be classified as having a distinct category of vasculitis, including polyarteritis nodosa (4 patients), Henoch-Schonlein purpura (1 patient), and drug-induced hypersensitivity vasculitis (6 patients), and 23 were classified in the group ‘other vasculitis, type unspecified.’ One patient had hepatitis B virus surface antigenemia, 2 had cryoglobulinemia, and 2 were coinfected by human T lymphotropic virus type I. Cytomegalovirus inclusions and antigens were found in endothelial cells in 1 patient. HIV antigens and genome were detected in perivascular cells of 2 of the 3 patients with necrotizing arteritis; in 1, HIV-like particles were seen by electron microscopy. Immune deposits were found in small vessel walls in 5 skin biopsy samples showing small vessel vasculitis and in the muscle of the 3 patients with necrotizing arteritis. Conclusion. A wide range of inflammatory vascular diseases may occur in HIV-infected individuals. Vascular inflammation appears multifactorial and may result from HIV-induced immunologic abnormalities and exposure to a variety of xenoantigens, such as HIV itself, other infectious agents, and drugs.

Five AIDS patients with previously diagnosed and treated toxoplasmosis presented with hyperdense precontrast CT approximately 6 months after the CNS infection. An MR study was performed in all cases. The CT hyperdensities were characterized on MR by a high signal intensity on T1 images in four cases. In two of these, pathological correlation confirmed hemorrhage. In the fifth case, MR findings were consistent with calcification, which was verified by pathological examination.

Background: Smoking prevalence is very high among people living with HIV/AIDS, and smoking is riskier for them than for HIV-seronegative people. Promoting smoking cessation among HIV-infected people is therefore an emerging public health priority. Raising cigarette prices is usually considered as one of the most effective ways to reduce smoking, but its effectiveness has never been studied among HIV-infected smokers. Methods: We studied the impact of cigarette price increases among HIV-infected smokers, with data extracted from the French cohort study APROCO-COPILOTE conducted between 1997 and 2007 among 1,146 patients. Data regarding respondents smoking status was collected every 8 months over the first 5 years, and every 12 months thereafter. Results: We found striking differences across transmission groups regarding socio-demographic background and smoking prevalence. The Intravenous Drug Use (IDU) group was characterised by a lower socioeconomic status, a higher smoking prevalence and a smaller decrease in this prevalence over the period 1997-2007. The homosexual group had a higher socioeconomic status, an intermediate smoking prevalence in 1997, and the highest rate of smoking decrease. In the dynamic multivariate analysis, smoking remained correlated with indicators of socioeconomic disadvantage and with infection through IDU. Aging and cigarette price increase had a negative impact on smoking among the homosexual group, but not for the IDU group. Conclusion: Among seropositive people, just as for the general population, poor smokers are poor quitters. Public health authorities should consider interventions which are not smoking-specific, but which contribute to improve the living conditions of the most deprived HIV-infected smokers.

A 25-year-old homosexual male with AIDS presented with a cauda equina syndrome clinically suggestive of cytomegalovirus (CMV) myeloradiculitis. He was treated with ganciclovir with transient improvement of neurological signs and died 4 months after onset of neurological signs. Neuropathological examination revealed human immunodeficiency virus (HIV) encephalitis, CMV subependymal encephalitis and CMV myeloradiculitis. The latter was characterised by myelin loss, Schwann cell proliferation and presence of CMV early antigens in the nuclei of S-100 protein-positive cells in the spinal roots. In the subependymal regions, morphologically characteristic multinucleated giant cells, positive for CD68, contained early CMV antigens (E13) in their nuclei and HIV antigens (gp41 and p24) in their cytoplasm. The observation that HIV and CMV can co-infect the same cell in vivo raises the possibility of a direct synergistic interaction of both viruses at cell level. This suggests that CMV may play a role as a co-factor in the pathogenesis of HIV encephalopathy.

Analgesics are required to prevent and treat postpartum pain, but breast-feeding may be contraindicated, because data on milk transfer are very limited. The present study was undertaken to quantify the transfer of ketoprofen and nalbuphine in milk. Eighteen patients gave their informed consent to participate and completed the study. Following delivery, they received ketoprofen (100 mg/12 hours) and nalbuphine (0.2 mg/kg/4 hours) as an intravenous bolus over 2 to 3 days for postpartum pain. Milk samples were collected during the 12 hours between the third and fourth ketoprofen administrations. Ketoprofen and nalbuphine concentrations were determined with high-performance liquid chromatography. The mean and maximum ketoprofen milk concentrations were 57+/-37 and 91+/-51 ng/mL, respectively. Assuming a milk volume of 150 mL/kg/day, the mean and maximum doses that a breast-fed neonate would ingest during one day are 8.5+/-5.5 and 13.6+/-7.6 microg/kg/day, respectively, and the relative infant dose is 0.31+/-0.17% of the weight-adjusted maternal daily dose. The mean and maximum nalbuphine milk concentrations were 42+/-26 and 61+/-26 ng/mL, respectively. Assuming a milk volume of 150 mL/kg/day, the mean and maximum doses that a breast-fed neonate would ingest during one day is 7.0+/-3.2 and 9.0+/-3.8 microg/kg/day, and the relative infant dose is 0.59+/-0.27% of the weight-adjusted maternal daily dose. Therefore, breast-feeding is permissible when ketoprofen and/or nalbuphine are administered to the mother to treat postpartum pain.

BACKGROUND: Efavirenz (EFV) is a highly active antiretroviral drug, use of which is associated with frequent (although transient) neurosensorial adverse reactions. Whether the use of EFV is associated with the risk of depression or suicide remains controversial. METHODS: ALIZE-ANRS (Agence Nationale de Recherches sur le SIDA et les Hepatites Virales) 099 was a 48-week randomized trial involving virologically suppressed, human immunodeficiency virus (HIV)-infected patients that compared the maintenance of a treatment regimen that contained protease inhibitors (177 subjects) with a switch to a once-daily combination of EFV, didanosine, and emtricitabine (178 subjects). We used the trial's adverse events reporting system and a self-administered Center for Epidemiologic Studies-Depression Scale questionnaire to assess depressive disorders. Determinants were studied using a multivariate proportional hazards model adjusted for antiretroviral treatment, sex, age, HIV risk factor, history of depression, hepatic disorder, alcohol abuse, and HIV-related or non-HIV-related events. RESULTS: Thirty cases of depressive disorder (26 cases of depression and 4 suicide attempts) occurred during treatment in 27 patients (12 patients 7% and 15 patients 8% in the protease inhibitor-based and EFV-based treatment arms, respectively; P = .56). In the proportional hazards model, only age (hazard ratio, 1.6 per 10 years younger; 95% confidence interval, 1.0-2.6) and a history of depressive disorder (hazard ratio, 5.0; 95% confidence interval, 2.1-12.0) were associated with a risk of depressive disorders. The proportion of depressive patients (24%), as determined on the basis of the Center for Epidemiologic Studies-Depression Scale data, was stable during the follow-up period, without difference between treatment groups. Patients with a history of depressive disorder were more frequently depressed (53%) than were those without such history (22%; P = .03). CONCLUSIONS: The frequency of depressive disorders was high in this population, but the disorders were not related to EFV treatment. Younger age and a history of depression are important determinants for depression and should be considered for early detection and case management. Language: en

Objective: To study immunologic and clinical responses to HAART in patients over 50 years old. Design and methods: A prospective cohort study which included 68 hospitals in France. A total of 3015 antiretroviral-naive patients, 401 of whom were aged 50 years or over, were enrolled following initiation of HAART. The influence of age on the mean CD4 cell count increase on HAART was studied by using a two-slope mixed model. Progression, defined by the occurrence of a new AIDS-defining event (ADE) or death, was studied by Cox multivariate analyses. Results: Among patients with baseline HIV RNA above 5 log copies/ml, CD4 mean increase during the first 6 months on HAART was +42.9 x 10 6 cells/l per month in patients under 50 years and +36.9 × 10 6 cells/I per month in patients over 50 years (P < 0.0001); subsequently, the respective monthly changes were +17.9 and +15.6 × 10 6 cells/l per month (P < 0.0001). Similar trends were observed in patients with baseline HIV RNA below 5 log copies/ml, and also after stratification for the baseline CD4 cell count. After a median follow-up of 31.5 months, 263 patients had a new ADE and 44 patients died. After adjustment for baseline characteristics, older patients had a significantly higher risk of clinical progression (hazard ratio (HR) = 1.52 [95% confidence interval (Cl), 1.15-2.00]) and were more likely to achieve a viral load below 500 copies/ml [HR = 1.23, (95% Cl, 1.11-1.38)]. Conclusion: Patients over 50 years of age have an immunologic response to HAART. However, their CD4 cell reconstitution is significantly slower than in younger patients, despite a better virologic response. This impaired immunologic response may explain their higher risk of clinical progression.

To describe the clinical features in HIV-1-infected patients treated with protease inhibitors (PIs) or not, and to determine factors related to occurrence of lipodystrophy (LD).We performed a cross-sectional analysis of 685 treated HIV-1-infected patients that were routinely followed in 6 Paris hospital centers between January and May 1999. Demographic data, familial and personal vascular risk factors, history of antiretroviral treatment, HIV plasma viral load, CD4 cell count, and metabolic data were collected. Clinical examination was based on an assessment of changes in abdominal, dorso-cervical, and breast girth and wasting of the limbs, face, and skin as quoted by the clinician.The mean age at inclusion in the study was 38 years; 29.5% were women. At study assessment, 77.5% of patients were PI-treated and 22.5% had never received a PI. LD was observed in 403 (58.8%) patients, of whom 340 were currently receiving a PI and 63 had never received a PI. More than half of the lipodystrophic patients had a mixed form (53.9%), while 25.3% were classified as exclusive lipoatrophic and 20.8% as exclusive hypertrophic. In multivariate analysis, older age, duration of antiretroviral treatment (ART), antiretroviral combinations including stavudine, antiretroviral combinations including a PI, AIDS status, and a low HIV RNA were independently associated with occurrence of LD.LD is frequently observed in PI-treated patients, but it is also observed in patients receiving an ART regimen without PIs. Our study suggests different underlying mechanisms, because immunovirological response to treatment as well as certain therapies were linked to the occurrence of LD. This hypothesis would be best clarified in a large prospective cohort of naive patients.

A 30-year-old AIDS patient with no history of cutaneous eruption, presented with rapidly progressive flaccid paraplegia, hypoesthesia, urinary retention, moderate psychomotor slowing and fever (39.8 degrees C), leading to death within 1 week. CD4 count was 290/mm3. Cerebrospinal fluid contained 210 white blood cells and 238 mg/100 ml protein. Neuropathology revealed HIV encephalitis and diffuse ventriculitis with Cowdry type A inclusions in the ependymal cells. Extensive necrotic and hemorrhagic changes with marked recrotizing vasculitis involved the entire spinal cord and spinal roots. Immunocytochemistry revealed numerous inclusion bodies positive for varicella-zoster virus (VZV) and negative for cytomegalovirus (CMV) and herpes simplex virus type 1 and 2, in ependymal cells, subpial glial cells, endothelial cells and Schwann cells. Electron microscopy confirmed herpes virus-like particles. In situ hybridization confirmed VZV genome in leptomeninges, brain, spinal cord and spinal roots. Comparable neuropathological findings and numerous VZV inclusion bodies were also found in the brain, spinal cord, and spinal roots of a 40-year-old AIDS patient who died from a fulminant ascending myeloradiculopathy previously reported as "necrotizing vasculitis of the nervous system". Direct infection of the brain by VZV, in AIDS patients, has been shown to cause leukoencephalitis and cerebral non-inflammatory vasculopathies. Our observations demonstrate that, in AIDS patients, VZV infection of the central nervous system may also be responsible for meningo-myelo-radiculitis possibly secondary to ventriculitis as in CMV infection. The role of VZV in the pathogenesis of some AIDS-related vasculitides seems also very likely.

Pathology of the central nervous system in 40 cases of acquired immune deficiency syndrome (AIDS) The central nervous system was examined in 40 AIDS patients who died between August 1982 and 1987. The cases included two children born to intravenous drug abusers and 38 male adults. The brains of eight patients who had no clinical or radiological evidence of central nervous system involvement showed non-specific changes which included microglial nodules, perivascular mononuclear cuffs, mineralization of blood vessels and granular ependymitis. In 32 brains from patients with neurological symptoms, toxoplasmosis was the most frequent finding (19 cases) manifested by multifocal, necrotic lesions or a diffuse pseudo-encephalitic process. Other opportunistic infections included cytomegalovirus (eight cases), progressive multifocal leucoencephalopathy (two cases), cryptococcosis (one case), aspergillosis (one case), multiple bacterial microabscesses (one case) and Mycobacterium avium intracellular (one case). Two patients had cerebral lymphoma. Subacute encephalitis with white matter lesions and multinucleated giant cells characteristic of HIV infection was present in 15 cases. Various combinations of all these infections were encountered in the same brain, sometimes in the same area and, occasionally, in the same cell.

Four patients with AIDS presented with a rapidly fatal global neurological illness. CT did not show any focal lesion and gross post mortem examination of the brain was normal in three of the four cases. Microscopic examination revealed numerous widespread microglial nodules in the brain parenchyma, most containing central toxoplama cysts or free tachyzoites. Such diffuse, non-necrotic, "encephalitic" forms of cerebral toxoplasmosis appear unique to AIDS and, to our knowledge, have not been documented previously. They represent a treatable, often misdiagnosed cause of diffuse neurological involvement in AIDS patients.

ObjectiveTo assess the impact of different patterns of adherence to highly active antiretroviral therapy (HAART), in particular, the relative impact of early and late adherence, on long-term immuno-virological response in HIV-infected individuals started on a protease inhibitor-containing regimen.DesignClinical, immuno-virological and self-reported adherence data were collected at 4 (M4), 12 (M12), 20 (M20), 28 (M28) and 36 (M36) months after HAART initiation in the French APROCO cohort.MethodsA standardized self-administered questionnaire classified patients as non-adherent, moderately or highly adherent at each visit. Stable viral suppression at both M28 to M36, and a CD4 cell increase >200 between M0 and M36 were used as outcome measures.ResultsOf the 582 patients followed regularly through M36, 360 patients had complete adherence data. Although 59.2% were highly adherent at M4, only 25.8% maintained consistent high adherence throughout the follow-up. High adherence at M4 was independently associated with both stable viral suppression at M28–M36 [OR (95% CI): 2.8 (1.4–5.5)] and a CD4 cell increase >200 during the same period [OR (95% CI): 3.9 (1.7–9.7)]. However, ‘moderately adherent’ patients between M12 and M36 had the same likelihood [OR (95% CI): 1.9 (1.1–3.2)] as patients who were always high adherent [OR (95% CI): 1.9 (1.1–3.2)] of achieving stable viral load suppression, relative to those who reported non-adherence episodes.ConclusionOptimizing adherence in the early months of treatment is crucial to ensure long-term immuno-virological success. Moderate deviations from high adherence during follow-up have a less negative impact. Priority should be given to interventions aimed to improve adherence in the early months of HAART.

To the Editor.— Dr Reichman 1 recently declared that he was concerned about the role of BCG vaccine in individuals at risk of human immunodeficiency virus (HIV) infection. Because we too think that this vaccination is dangerous, we report herein on a healthy individual who was given BCG vacine and later developed acquired immunodeficiency syndrome and also disseminated Mycobacterium bovis infection related to his previous vaccination. Report of a Case.— A 32-year-old Algerian man, living in France since the age of 12 years, presented in April 1988 because of chronic diarrhea. Crohn's disease was suspected. He was successfully treated with 1 mg/kg per day of prednisone and 1.5 g/d of metronidazole. At that time, an extensive search for microorganisms was unsuccessful. Prednisone therapy was slowly tapered to 5 mg/d in November 1988, when severe bilateral Pneumocystis carinii pneumonia developed. He was successfully treated with sulfamethoxazole and trimethoprim. No other microorganisms