Showing papers by "Institut de veille sanitaire published in 2007"

Recommendations for Surveillance of Clostridium difficile-Associated Disease

Abstract: Background. The epidemiology of Clostridium difficile–associated disease (CDAD) is changing, with evidence of increased incidence and severity. However, the understanding of the magnitude of and reasons for this change is currently hampered by the lack of standardized surveillance methods. Objective and methods. An ad hoc C. difficile surveillance working group was formed to develop interim surveillance definitions and recommendations based on existing literature and expert opinion that can help to improve CDAD surveillance and prevention efforts. Definitions and recommendations. A CDAD case patient was defined as a patient with symptoms of diarrhea or toxic megacolon combined with a positive result of a laboratory assay and/or endoscopic or histopathologic evidence of pseudomembranous colitis. Recurrent CDAD was defined as repeated episodes within 8 weeks of each other. Severe CDAD was defined by CDAD‐associated admission to an intensive care unit, colectomy, or death within 30 days after onset. Case pat...

Update of Clostridium difficile-associated disease due to PCR ribotype 027 in Europe.

Abstract: Recent outbreaks of Clostridium difficile-associated diarrhoea (CDAD) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America, Japan and Europe. Definitions have been proposed by the European Centre of Disease Prevention and Control (ECDC) to identify severe cases of CDAD and to differentiate community-acquired cases from nosocomial CDAD (http://www.ecdc.europa.eu/documents/pdf/Cl_dif_v2.pdf). CDAD is mainly known as a healthcare-associated disease, but it is also increasingly recognised as a community-associated disease. The emerging strain is referred to as North American pulsed-field type 1 (NAP1) and PCR ribotype 027. Since 2005, individual countries have developed surveillance studies to monitor the spread of this strain. C. difficile type 027 has caused outbreaks in England and Wales, Ireland, the Netherlands, Belgium, Luxembourg, and France, and has also been detected in Austria, Scotland, Switzerland, Poland and Denmark. Preliminary data indicated that type 027 was already present in historical isolates collected in Sweden between 1997 and 2001.

Unacceptably High Mortality Related to Measles Epidemics in Niger, Nigeria, and Chad

Abstract: Background Despite the comprehensive World Health Organization (WHO)/United Nations Children’s Fund (UNICEF) measles mortality–reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain highburden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N’Djamena (Chad), and Adamawa State (Nigeria).

Role of Sex, Age, Previous Valve Lesion, and Pregnancy in the Clinical Expression and Outcome of Q Fever after a Large Outbreak

Abstract: Background Q fever is a zoonosis caused by Coxiella burnetii. After a large outbreak occurred in the Chamonix Valley in the French Alps in 2002, an extensive surveillance was conducted, to describe the variations in the clinical expression of acute Q fever according to host factors, as well as to monitor the risk of evolution of acute Q fever to chronic Q fever in patients at risk. Methods Three groups of patients with risk factors for evolution of acute Q fever to chronic Q fever were considered: 376 pregnant women, 19 immunocompromised patients, and 91 patients with valvular or vascular abnormalities. A group of 578 people without risk factors for evolution of acute Q fever to chronic Q fever was also tested. Diagnosis of Q fever was based on serologic testing by immunofluorescence assay. Results Between 30 August 2002 and 31 July 2003, a total of 1946 serum samples obtained from 1064 persons were tested. A total of 101 patients (9.3%) had acute Q fever diagnosed, and 5 patients (0.5%) had chronic Q fever diagnosed. A diagnosis of acute Q fever was established for 11 pregnant women (2.6% of 379 pregnancies), 5 patients with valvular disease (5.5%), and 85 people without risk factors (14.7%) (71 [27.9%] of 254 symptomatic patients and 14 [4.3%] of 324 asymptomatic patients). A new pregnancy in a woman with negative results of serologic tests for Q fever exposes the woman to a new risk for acute Q fever able to evolve to chronic Q fever. The rates of clinical expression were 90.6% in adult men, 75% in adult women, and 33.3% in children, and they were significantly lower (9.1%) in pregnant women. Evolution to chronic Q fever was observed in 5 patients. Conclusion This study emphasizes the importance of active surveillance in postepidemic conditions, especially among patients at risk, as well as the importance of systematic serologic testing during pregnancy.

Surveillance of enteroviruses in France, 2000-2004.

Abstract: In the context of poliomyelitis eradication, a reinforced sentinel laboratory network for surveillance of enteroviruses (RSE) was implemented in France in January 2000, and the purpose of this report is to describe the results of the five first years of surveillance. From 2000 to 2004, the RSE laboratory network performed detailed surveillance of the circulating enteroviruses. No wild-type poliovirus was isolated from humans during the 5 years of surveillance, although two imported vaccine polioviruses were detected. During the same period, Sabin-like polioviruses were identified on five occasions in the sludge from sewage treatment plants, but no wild-type poliovirus was found. Over the 5 years of surveillance, information was collected from 192,598 clinical samples, including 39,276 cerebrospinal fluid specimens, of which 14.7% were positive for enteroviruses, 45,889 stool samples (4.3% positive for enteroviruses), 70,330 throat swabs (2.2% positive) and 14,243 sera (1.4% positive). The ten main nonpolio enteroviruses typed were as follows, in decreasing order of frequency: E-30, E-13, E-6, CV-B5, E-11, CV-B4, E-9, E-7, CV-B1, and CV-B2. During the year 2000, an outbreak of aseptic meningitis due to three main enteroviruses (echoviruses type 30, 13, and 6) was monitored. Continued surveillance of enteroviruses is important to alert physicians and public health officials to changes in disease trends. Although the geographical coverage of the RSE network as well as the percentage of enteroviruses identified must be improved, the large number of samples tested for enteroviruses shows the ability of virology laboratories to detect the circulation of enteroviruses and to report the possible identification of poliovirus (wild-type, vaccine-derived, or Sabin-like).

Monitoring the Dynamics of the HIV Epidemic Using Assays for Recent Infection and Serotyping among New HIV Diagnoses: Experience after 2 Years in France

Abstract: Background. New tools to better monitor dynamics of human immunodeficiency virus (HIV) transmission are needed. Methods. National surveillance of newly HIV diagnoses included the collection of dried serum spots to identify both recent infections (<6 months) and HIV serotypes. Multivariate analyses were used to identify factors associated with recent infection and infection with non-B subtypes. Results. Between 2003 and March 2005, 7902 new HIV diagnoses were reported. The overall proportion of recent infections was 24.9% (95% confidence interval, 23.8%-26.0%) and was highest among men who have sex with men (MSM; 46%). Recent infection was associated with being an MSM, <30 years old, of French nationality, and living in Paris. Nearly half of newly HIV-1 diagnoses were with non-B subtypes. The highest proportion of non-B infections was reported among African heterosexual persons (81%), but important proportions were reported among French heterosexual persons (34%) and MSM (12%). Being infected by a non-B subtype was independently associated with being African, <30 years old, heterosexual, and living in Paris. The proportion of HIV-2 infection was 1.9%, and 11 cases of HIV-1 group O infection were identified, mainly among West Africans. Conclusions. There is evidence of high levels of HIV transmission among MSM in France and transmission of non-B subtypes within the indigenous French population.

Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5.

Abstract: Gfi1 transcriptionally governs hematopoiesis, and its mutations produce neutropenia. In an effort to identify Gfi1-interacting proteins and also to generate new candidate genes causing neutropenia, we performed a yeast two-hybrid screen with Gfi1. Among other Gfi1-interacting proteins, we identified a previously uncharacterized member of the PR domain-containing family of tumor suppressors, PRDM5. PRDM5 has 16 zinc fingers, and we show that it acts as a sequence-specific, DNA binding transcription factor that targets hematopoiesis-associated protein-coding and microRNA genes, including many that are also targets of Gfi1. PRDM5 epigenetically regulates transcription similarly to Gfi1: it recruits the histone methyltransferase G9a and class I histone deacetylases to its target gene promoters and demonstrates repressor activity on synthetic reporters; on endogenous target genes, however, it functions as an activator, in addition to a repressor. Interestingly, genes that PRDM5 activates, as opposed to those it represses, are also targets of Gfi1, suggesting a competitive mechanism through which two repressors could cooperate in order to become transcriptional activators. In neutropenic patients, we identified PRDM5 protein sequence variants perturbing transcriptional function, suggesting a potentially important role in hematopoiesis.

Pertussis surveillance in french hospitals : Results from a 10 year period

Abstract: We present 10 years of results from a paediatrician hospital network surveillance in France, set up in 1996 to monitor the trend of pertussis (whooping cough) in children and the impact of the vaccination strategies. Microbiologists from 43 hospitals that participate in the network on a voluntary basis notify pertussis diagnosis, and paediatricians complete a questionnaire for the infants under 6 months that fulfil the microbiological, clinical or epidemiological case definition. The network covers about 30% of pertussis cases seen in French hospitals. Around 300 cases of pertussis are notified in France annually. Two peaks occurred in 1997 and 2000. The estimated national incidence rate for the 0-2 months old children is 276/100 000 on average. Since March 1996, the network has described 1688 cases under-6 month. The male-female ratio was 1.0 and 63 % were less than 3 months of age. Most patients (96%) were hospitalised with 17% admitted in intensive care. The case fatality ratio was 2% with 32 deaths. Vaccination status was confirmed through medical records for 83% of children and 78% were not vaccinated. The source of contamination was identified for 53 % of cases and was in majority the parents. The Renacoq data confirmed the risk for young children, the role of parents as source of infection and the need of a pertussis vaccination in time. Vaccination is now recommended to adults who hope to become parents, and this should help to reduce this burden.

Campylobacter antimicrobial drug resistance among humans, broiler chickens, and pigs, France.

Abstract: We describe isolates from human Campylobacter infection in the French population and the isolates' antimicrobial drug resistance patterns since 1986 and compare the trends with those of isolates from broiler chickens and pigs from 1999 to 2004. Among 5,685 human Campylobacter isolates, 76.2% were C. jejuni, 17.2% C. coli, and 5.0% C. fetus. Resistance to nalidixic acid increased from 8.2% in 1990 to 26.3% in 2004 (p<10-3), and resistance to ampicillin was high over time. Nalidixic acid resistance was greater for C. coli (21.3%) than for C. jejuni (14.9%, p<10-3). C. jejuni resistance to ciprofloxacin in broilers decreased from 31.7% in 2002 to 9.0% in 2004 (p = 0.02). The patterns of resistance to quinolones and fluoroquinolones were similar between 1999 and 2004 in human and broiler isolates for C. jejuni. These results suggest a potential benefit of a regulation policy limiting use of antimicrobial drugs in food animals.

Two consecutive large outbreaks of Salmonella enterica serotype Agona infections in infants linked to the consumption of powdered infant formula.

Abstract: Background:An increase of isolation of Salmonella Agona was observed in January through February 2005 among infants in France.Methods:Case–control study, food trace-back and microbiologic investigations were promptly carried out.Results:A total of 141 confirmed cases <12 months of age were identifie

Decrease in the stroke case fatality rates in a French population-based twenty-year study. A comparison between men and women.

Abstract: Background: The aim of the study was to estimate trends in stroke case fatality in a French population-based study over the last 20 years, and to compare trends in men and women. &l

What Is Tuberculosis Surveillance in the European Union Telling Us

Abstract: Background. Today's European Union (EU) encompasses countries with diverse patterns of tuberculosis epidemiology. Methods. We explored national tuberculosis data for 1999-2003 reported to the EuroTB surveillance network. We analyzed only complete, representative data for drug resistance (from 15 countries) and treatment outcomes (from 19 countries). Results. Between 1999 and 2003, overall tuberculosis notification rates in the 25 EU countries decreased by 4% each year, down to 14 cases per 100,000 population in 2003, but Italy and the United Kingdom registered increases because of tuberculosis in immigrants. In 2003, EU countries reported 62,743 tuberculosis cases; of these, 76% were in persons who were previously untreated, 22% were in persons >64 years old, and 30% were in foreigners (the percentage in individual countries ranged from 2% to 75%). In Estonia, Latvia, and Lithuania, resistance to isoniazid and rifampicin occurred in 15%-23% of cases in which resistance testing was performed, but it was uncommon elsewhere (median resistance, 1%). Among previously untreated culture-positive patients with pulmonary tuberculosis, 76% had successful outcome (the percentage in individual countries ranged from 54% to 100%); among these patients, the probability of successful outcome diminished with advancing age. Of 9414 patients with AIDS reported in the EU, 2207 (23%) had tuberculosis as the initial defining illness, representing 3% of all tuberculosis cases notified that year (the percentage in individual countries ranged from 0% to 10%). The prevalence of HIV infection among patients with tuberculosis was highest in Portugal (16.1%) and Spain (9.6%), but it increased in Estonia (from 0.1% to 2.9%) and in Latvia (from 0.5% to 2.3%) between 1999 and 2003. Conclusions. Surveillance data would be more comparable if more countries reported exhaustive and representative data. Drug resistance is low in most EU countries other than former Soviet states. HIV infection and tuberculosis comorbidity is important in certain countries. Prevention and control of tuberculosis in the EU should target groups at higher risk of infection or death, including foreigners and the elderly population.

Encéphalites infectieuses : données et limites du PMSI pour l'étude épidémiologique, France métropolitaine 2000-2002

Abstract: Many virus and bacteria can cause encephalitis but are rarely identified as the aetiological agent by individual diagnosis. In France, the only continuous source of information about encephalitis is the national hospital medical database (NHMD). Data from the VIH-negative patients recorded in mainland France between 2000 and 2002 with a diagnosis of encephalitis were extracted and analysed according to demographic, geographical and temporal distribution. Hospitalisation details were described. An average of 1200 patients was recorded each year. They were residents of all French districts and equally hospitalized in university hospitals and non university hospitals. Their mean age was 38, and most were men. The aetiological diagnosis was unknown for 80%. The most frequent aetiological diagnosis was herpes simplex virus in adults, and VZV virus in children. These results give us some clues to design a national study on encephalitis. The study will be implemented in mainland France in 2007 and will last one year. We invite all voluntary hospitals to include their encephalitic patients in our study.

Short-term effect of pollen exposure on antiallergic drug consumption

Abstract: Background Several studies have investigated the association between pollen exposure and asthma emergency admissions, but only 2 have investigated the effect of airborne allergens on consultations for rhinitis or conjunctivitis and none has used drug consumption as the health indicator. Objective To analyze the short-term association between pollen exposure and antiallergic drug consumption in the urban area of Clermont-Ferrand, France, taking into account the potentially confounding effect of air pollution and meteorological factors. Methods We used the French health insurance database to select all individuals from the Clermont-Ferrand urban area having benefited from reimbursement for antiallergic treatment from January 1, 2000, through December 31, 2001, and from January 1, 2003, through December 31, 2004. An episode of treated allergic rhinitis, rhinosinusitus, or conjunctivitis (ARC) was defined as the association of an oral antihistamine and a local antiallergic drug on the same prescription. The relations between daily changes in pollen concentrations and daily changes in the number of treated ARC cases were analyzed using a Poisson regression model with penalized spline functions. Results The risk of treated ARC associated with an interquartile increase in pollen concentration increased significantly for Poaceae (5%, P Fraxinus (7%, P Betula (7%, P Corylus (2%, P Fraxinus pollen and in people younger than 65 years for Betula pollen. The effect was mainly concentrated on the present day, except for Poaceae pollens, for which the risk remained significantly ( P Conclusions This study showed a significant increase in treated ARC cases related to Poaceae, Fraxinus , and Betula . Specific risks are difficult to evaluate for species that share the same pollination period. Time-series studies based on drug consumption are useful to highlight and to supervise pollen-related diseases requiring ambulatory care.

Death rates from malaria epidemics, Burundi and Ethiopia.

Abstract: Death rates exceeded emergency thresholds at 4 sites during epidemics of Plasmodium falciparum malaria in Burundi (2000-2001) and in Ethiopia (2003-2004). Deaths likely from malaria ranged from 1,000 to 8,900, depending on site, and accounted for 52% to 78% of total deaths. Earlier detection of malaria and better case management are needed.

Trends in the incidence of transient ischemic attacks, premorbid risk factors and the use of preventive treatments in the population of Dijon, France from 1985 to 2004.

Abstract: Background: We describe the epidemiological trends of transient ischemic attack (TIA) in a 20-year population-based pilot study. Methods: Trends in the incidence,

Estimating infra-national and national thyroid cancer incidence in France from cancer registries data and national hospital discharge database.

Abstract: Objective As in many countries, cancer registries cover only part of the population in France. Incidence/mortality ratio observed in registries is usually extrapolated to produce national estimates of cancer incidence. District-level estimates are not currently available. For cancer sites such as thyroid, the incidence/mortality ratio widely varies between districts, and alternative indicators must be explored. This study aims to produce national and district-level estimations of thyroid cancer incidence in France, using the ratio between incidence and hospital-based incidence.

French situation concerning the Swedish Chlamydia trachomatis variant.

Abstract: In 2006, a plasmid deletion mutant of Chlamydia trachomatis was identified in Sweden that can not be detected with those commercial tests targeting the deleted area. In order to study the spread of this strain in France, a laboratory-based surveillance system was set up by the National Reference Centre for Chlamydiae and the Institut de Veille Sanitaire. Among 1,141 C. trachomatis-positive specimens from all over France, the new variant was only detected in one case. This case was a non-French resident consulting a sexually transmitted infections clinic. Although the new variant does not seem to be established in France as yet, surveillance based on the testing of C. trachomatis-positive samples from all over France continues.

Evolution des hospitalisations pour asthme en France métropolitaine, 1998-2002

Abstract: Resume Introduction Les hospitalisations pour crise d’asthme etant un indicateur de defaut de prise en charge, les tendances des hospitalisations pour asthme en France metropolitaine entre 1998 et 2002 ont ete analysees. Methodes A partir des donnees du PMSI, les sejours pour asthme ont ete definis par les codes J45-J46 (CIM-10) en diagnostic principal et ceux pour insuffisance respiratoire aigue (IRA) associee a un asthme par les codes J96.0 en diagnostic principal et J45-J46 en diagnostic associe. Resultats Le taux standardise d’hospitalisation pour asthme a diminue de 10,8 en 1998 a 8,6/10 000 en 2002 (-5 %/an). Une diminution significative etait observee chez les plus de 10 ans (de -5 %/an chez les 10-14 a -9 %/an chez les ≥ 50 ans). On observait une augmentation non significative du taux d’hospitalisation pour IRA associee a un asthme. Conclusion Les taux d’hospitalisation pour asthme ont diminue entre 1998 et 2002 chez les 10 ans ou plus. Cette reduction reflete probablement des modifications dans le traitement preventif des patients asthmatiques. Une evolution dans les pratiques de codage ou les criteres d’hospitalisation ne peut toutefois etre exclue.

HIV/AIDS in Europe: epidemiological situation in 2006 and a new framework for surveillance.

Abstract: The European dedicated surveillance network EuroHIV (formerly the European Centre for the Epidemiological Monitoring of AIDS) has been carrying out surveillance based on AIDS case reporting since 1984 [1] and HIV case reporting since 1999

Nosocomial infections and community clusters of pertussis in France, 2000-2005.

Abstract: Pertussis is not a notifiable disease in France. In addition to a paediatric hospital sentinel surveillance system, pertussis epidemiological data have, since 1996, been gathered through the voluntary notification of community clusters by general practitioners, and since 2001 by the statutory notification of nosocomial infection to the relevant local health authority. The local health authority forwards the information to the French National Institute for Surveillance (InVS). The objective of this study was to analyse pertussis data outside the routine paediatric hospital sentinel surveillance system. We gathered all the information concerning healthcare-associated infections and community clusters of pertussis (specific forms, investigation reports, emails etc.) reported to the InVS between 2000 and 2005. The InVS received and analysed 67 reports with a total of 595 cases. Almost half of the reports (n=31) came from hospitals, and healthcare workers were usually first affected. Control measures were put in place in 22 healthcare facilities and the average duration of an outbreak episode was 48 days. Outside healthcare facilities, clusters were reported also from 17 daycare facilities or schools and five workplaces. Among the 595 cases, six deaths occurred in children under seven months of age. Pertussis is still occurring in France and affects those who are not or who are no longer protected by the vaccine. Infection of infants within the household could be prevented if their parents and siblings were immunised. The number and size of pertussis clusters in hospitals could be reduced through immunisation of health staff, and timely and adequate outbreak management.

Hepatitis A and B vaccination and public health.

Abstract: The introduction and implementation of hepatitis B vaccination programmes in areas of high endemicity has been very stressful. However, this initial accomplishment has led to the reassessment of priorities in some countries which could undermine these early successes. Work still remains to be done to support and implement interventions that will bring us closer to the WHO goal and to the control of hepatitis B in the community at large. Hepatitis A vaccine strategy for immunizing toddlers is shifting to those countries with intermediate endemicity where increasing morbidity in adults is being observed. Accumulating evidence indicates that such programmes can result in impressive reductions in the incidence of hepatitis A by herd immunity. Monitoring of these populations to determine durability of protection will be important to avoid shifting the infection to the older age population, when symptoms are more likely to occur. National policies need to consider hepatitis A vaccination in the context of other public health priorities.

Survie des patients atteints de cancer en France: principaux résultats de la première étude du réseau des registres français des cancers (Francim)

Abstract: Nous rapportons ici les principaux resultats de la premiere etude de survie portant sur l’ensemble des donnees des registres de cancers du reseau Francim. Les donnees de survie de 205 562 cas enregistres entre 1989 et 1997 ont ete analysees. La survie relative a cinq ans standardisee pour l’âge etait la suivante: 84 % pour le cancer du sein, 77 % pour le cancer de la prostate, et chez l’homme, et la femme respectivement, 55 et 57 % pour le cancer du colon, 12 et 16 % pour le cancer du poumon. Le pronostic etait souvent meilleur chez la femme. Pour certains cancers, les cas les plus recents avaient un meilleur pronostic (notamment sein, prostate, thyroide). Un âge avance au diagnostic s’accompagnait d’une mortalite en exces plus importante que celle observee chez les sujets jeunes. Cet effet s’observait cependant souvent au cours de la premiere annee suivant le diagnostic et beaucoup moins au-dela.

International epidemic intelligence at the Institut de Veille Sanitaire, France.

Abstract: The French Institute for Public Health Surveillance monitors health events of potential international importance occurring worldwide to provide timely warning to French health authorities. We reviewed the nature and place of occurrence of the last 200 events. From an individual country’s perspective, the need for multiple sources is emphasized.

Sensitivity analysis in summary measure of population health in France

Abstract: Background: The aim of this study is to provide estimates of the French burden of disease, using the WHO Global Burden of Disease methodology and to perform sensitivity analysis on different set of mortality data. Methods: The burden of disease is measured by disability-adjusted life years (DALYs) that take into account both mortality and morbidity data. Results were obtained using French mortality data for the years 2000 and 2001 and morbidity data estimated by WHO for France. Sensitivity analyses were conducted using different mortality data sets and various life tables as mortality norms. Calculations were also performed with and without discounting and age-weighting. Results: In France, the annual burden of disease was about 12.4 million DALYs. Depending on the mortality data set and the choice of social values used for calculation, results could be quite different. The use of WHO estimates for mortality resulted in an underestimation of 2.6% of total DALYs with respect to French data. Changes of the mortality norm imply changes in the number of years of life lost (YLLs), whereas the use of discounting and age-weighting mainly modifies the ranking of diseases. Conclusion: DALYs constitute a summary measure of population health, which is a powerful tool for the grading of health problems, allowing to compare fatal and non-fatal diseases. Nevertheless, the validity of results obtained depends primarily on the validity of the input data. Collecting morbidity data (mainly incidence) at the national level is hence an important step in order to assess more accurately the specific burden of diseases in France.

Differential improvement in survival among patients with AIDS after the introduction of HAART.

Abstract: We explored changes in the survival of patients with AIDS (PWA) according to the availability of antiretroviral drugs (1994–2002). We tested whether changes in the hazard ratio of progression to death (HR) have been homogeneous among various groups of PWA. We included 4158 PWA diagnosed in Paris, notified to the French National Surveillance Institute by 2002. Four calendar periods were defined: monotherapy (1994–95), bitherapy-HAART transition (1996), early HAART (1997–99), late HAART (2000–October 2002). HR were calculated with Cox models, including the calendar period, modelled as a time dependent covariate. Models were stratified by age, transmission category, CD4 cell count, and AIDS-defining illnesses (ADI) group. Cumulative survival at 60 months increased from 44.0% (before July 1996) to 75.6% (after July 1996) and median survival increased from 31.9 months to >76 months. Adjusted HR reached a minimum in the late HAART period (HR 0.22, 95% CI: 0.19–0.26). No difference in the decrease of th...