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ABSTRACT: BACKGROUND: The main source of key medical information consists in original articles published in peer-reviewed biomedical journals. Reported studies use increasingly sophisticated statistical and epidemiological approaches that first require a solid understanding of core methods. However, such understanding is not widely shared among physicians. Our aim was to assess whether the basic statistical and epidemiological methods used in original articles published in general biomedical journals are taught during the first years of the medical curriculum in France. METHODS: We selected original articles published in The New England Journal of Medicine, The Lancet, and The Journal of the American Medical Association, over a period of six months in 2007 and in 2008. A standardized statistical content checklist was used to extract the necessary information in the "Abstract", "Methods", "Results", footnotes of tables, and legends of figures. The methods used in the selected articles were compared to the national program and the public health program of biostatistics and epidemiology taught during the first six years of medical school. RESULTS: The 237 analyzed original articles all used at least one statistical or epidemiological method. Descriptive statistics, confidence interval and Chi(2) or Fisher tests, methods used in more than 50% of articles, were repeatedly taught throughout the medicine curriculum. Measures of association, sample size, fit and Kaplan-Meier method, used in 40 to 50% of articles, were specifically taught during training sessions on critical reading methods. Cox model (41% of articles) and logistic regression (24% of articles) were never taught. The most widely used illustrations, contingency tables (92%) and flowcharts (48%), were not included in the national program. CONCLUSION: More teaching of the core methods underlying the understanding of sophisticated methods and illustrations should be included in the early medical curriculum so that physicians can read the scientific literature critically for their medical education.
Revue d Épidémiologie et de Santé Publique 04/2013; · 0.78 Impact Factor
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D. Costagliola,
R. K. Lodwick,
B. Ledergerber,
C. Torti,
A. van Sighem,
D. Podzamczer,
A. Mocroft,
M. Dorrucci,
B. Masquelier,
A. de Luca, [......],
R. Zangerle,
X. Duval,
S. Perez Hoyos,
L. Meyer,
J. Ghosn,
C. Fabre-Colin,
Kjaer J., G. Chêne,
J. Garup,
A. Phillips
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ABSTRACT: BACKGROUND: Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09. METHODS: In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF. FINDINGS: 28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19.5% in 2000 to 57.9% in 2009 (adjusted p<0.0001). Incidence of AIDS decreased from 7.7 per 100 person-years in 2000-02 to 2.3 in 2008 and 1.2 in 2009 (adjusted p<0.0001). Mortality decreased from 4.0 per 100 person-years between 2000 and 2002 to 1.9 in 2007 and 1.4 in 2008 (unadjusted p=0.023), but the trend was not significant after adjustment (p=0.22). INTERPRETATION: A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000-09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs. FUNDING: UK Medical Research Council.
The Lancet Infectious Diseases 01/2012; 12(2):119-127. · 17.39 Impact Factor
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ABSTRACT: The aim of this study was to determine factors associated with complete satisfaction with the care provided (satisfaction with physicians and satisfaction with services and organization) among HIV-infected patients followed up in the French ANRS CO8 APROCO-COPILOTE cohort. Analyses focused on cross-sectional data collected during the ninth year of cohort follow-up. Satisfaction with care, sociodemographic characteristics, and behavioral data were collected using self-administered questionnaires, while clinical data were derived from medical records. Complete satisfaction with care was defined as being 100% satisfied. Two logistic regression models were used to identify predictors of (1) complete satisfaction with physicians (n=404) and (2) complete satisfaction with services and organization (n=396). Sixteen percent of patients were completely satisfied with physicians, while 15.9% were completely satisfied with services and organization. Being older and reporting fewer discomforting antiretroviral therapy (ART) side effects were factors independently associated with complete satisfaction with both physicians and services and organization. Strong support from friends and absence of hepatitis C (HCV) co-infection were independently associated with complete satisfaction with physicians, while strong support from one's family and comfortable housing conditions were independently associated with complete satisfaction with services and organization. Even after nine years of follow-up, social vulnerabilities still strongly influence HIV-infected patients' interactions with the health care system. Day-to-day experience with the disease, including perceived treatment side effects, appears to play a key role in the quality of these interactions. More attention should be given to patient satisfaction, especially for socially vulnerable patients, in order to avoid potentially detrimental consequences such as poor adherence to ART.
AIDS Care 10/2011; 24(4):434-43. · 1.60 Impact Factor
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ABSTRACT: The aim of the study was to determine whether the chemokine (C-C motif) receptor 5 (CCR5) Delta32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1-infected patients.
The genetic substudy of the Agence Nationale de Recherche sur le SIDA (ANRS) CO8 APROCO-COPILOTE cohort included 609 patients who started protease inhibitor-containing cART in 1997-1999. Patients were considered to have a sustained virological response if all plasma HIV RNA measurements in the period considered were <500 HIV-1 RNA copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Delta32 (Delta32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and from month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV RNA, CD4 cell count, antiretroviral exposure status, time spent on antiretroviral therapy at years 3 and 5 and adherence to treatment (month 4 to year 3 or 5).
A sustained virological response was more frequent in Delta32/wt than in wt/wt patients from month 4 to year 3, with 66%vs. 52% of patients, respectively, showing a sustained response (P=0.02); after adjustment for potential confounders, the association of Delta32 with a sustained response was nearly significant (P=0.07). A sustained virological response was also more frequent in Delta32/wt patients up to year 5, with 48% showing a sustained response vs. 35% of wt/wt patients (P=0.01); after adjustment, Delta32 remained significantly associated with a sustained virological response up to year 5 (P=0.04). There was no association with CD4 response.
The Delta32 deletion in Delta32/wt patients is associated with a beneficial virological response to cART in the long term. Whether this association is a direct effect of the Delta32 deletion remains unclear and requires confirmation in further observational studies.
HIV Medicine 04/2010; 11(4):239-44. · 3.01 Impact Factor
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Y Yazdanpanah,
C Fagard,
D Descamps,
A M Taburet,
C Colin,
B Roquebert,
C Katlama,
G Pialoux,
C Jacomet,
C Piketty,
D Bollens,
J M Molina, G Chêne
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ABSTRACT: The introduction of 2 or 3 fully active drugs in human immunodeficiency virus (HIV)-infected patients receiving failing antiretroviral therapy is a key determinant of subsequent treatment efficacy. The aim of this study was to assess the safety and efficacy of a regimen containing raltegravir, etravirine, and darunavir/ritonavir for treatment-experienced patients infected with multidrug-resistant HIV.
Patients enrolled in this phase II, noncomparative, multicenter trial were naive to the investigational drugs and had plasma HIV RNA levels >1000 copies/mL, a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors (NNRTI), > or =3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) mutations, and < or =3 darunavir and NNRTI mutations. The primary end point was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks.
A total of 103 patients enrolled in the study. At baseline, genotypic resistance profiles showed a median of 4 primary protease inhibitor mutations, 1 NNRTI mutation, and 6 NRTI mutations. In addition to the investigational drugs, 90 patients (87%) received optimized background therapy that included NRTIs (86 patients) or enfuvirtide (12 patients). At week 24, 90% of patients (95% confidence interval, 85%-96%) had an HIV RNA level <50 copies/mL. At week 48, 86% (95% confidence interval, 80%-93%) had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm(3). Grade 3 or 4 clinical adverse events were reported in 15 patients (14.6%). Only 1 patient discontinued the investigational antiretroviral regimen, because of an adverse event.
In patients infected with multidrug-resistant virus who have few remaining treatment options, the combination of raltegravir, etravirine, and darunavir/ritonavir is well tolerated and is associated with a rate of virologic suppression similar to that expected in treatment-naive patients.
Clinical Infectious Diseases 11/2009; 49(9):1441-9. · 9.15 Impact Factor
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ABSTRACT: To determine risk factor for non-AIDS severe clinical events in HIV-infected patients on long-term combination antiretroviral therapy (cART).
A validation committee reviewed each severe clinical event that occurred in the APROCO/COPILOTE (ANRS CO8) cohort that enrolled 1281 patients in 1997-1999 at the initiation of cART containing protease inhibitor. Probability of the occurrence of a first non-AIDS, cART-related, and AIDS-defining event was estimated, and potential determinants were studied using Cox regression models.
During a median follow-up of 7.3 years, the incidence of non-AIDS events was higher than that of cART-related and AIDS-defining events (10.5, 3.6, and 2.6 per 100 patient-years, respectively). Bacterial (mainly airway) infections were the most frequent non-AIDS events (23.4%) followed by non-AIDS-defining malignancies and cardiovascular events (both 9.5%). Factors independently associated with the occurrence of a first non-AIDS event were age >60 years [hazard ratio (HR) 2.1; 95% confidence interval (CI): 1.3 to 3.2] and CD4 <100 cells per milliliter (HR 2.5; 95% CI: 1.8 to 3.6) but also plasma HIV RNA >4 log10 copies per milliliter at the time of the event (HR 1.9; 95% CI: 1.5 to 2.5).
Optimization and permanent continuation of long-term antiretroviral therapy in HIV-infected patients is the best strategy to prevent or reduce the occurrence of non-AIDS severe morbidity.
JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2009; 51(4):407-15. · 4.43 Impact Factor
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E Rosenthal,
D Salmon-Céron,
C Lewden,
V Bouteloup,
G Pialoux,
F Bonnet,
M Karmochkine,
T May,
M François,
C Burty,
E Jougla,
D Costagliola,
P Morlat, G Chêne,
P Cacoub
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ABSTRACT: More than 10 years after the introduction of combination antiretroviral therapy (cART), we examined the trend in the proportion of deaths caused by end-stage liver disease (ESLD) in HIV-infected adults in France between 1995 and 2005.
In 2005, 34 departments prospectively recorded all deaths in HIV-infected patients who were followed in those departments (around 24 000).
were compared with those of four previous cross-sectional surveys conducted since 1995 using the same methodology. Results Among 287 reported deaths in 2005, 100 (35%) were related to AIDS, and 48 (17%) to ESLD. Three out of four patients who died from ESLD-related causes had chronic hepatitis C. Excessive alcohol consumption was reported in approximately half of the patients (48%). At death, 62% of patients had undetectable HIV viral load and the median CD4 count was 237 cells/microL. From 1995 to 2005, the proportion of deaths caused by ESLD increased from 2 to 17% (P<0.001). The proportion of deaths caused by hepatocellular carcinoma increased from 5% in 1995 to 25% in 2005 (P=0.0337).
Over the 10 years from 1995 to 2005, the proportion of deaths caused by hepatitis C virus-related ESLD has increased in HIV-infected patients. ESLD is currently a leading cause of death in this population, with hepatocellular carcinoma representing a quarter of liver-related deaths. Recommendations for the detection of hepatocellular carcinoma should be strictly applied in these patients.
HIV Medicine 03/2009; 10(5):282-9. · 3.01 Impact Factor
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ABSTRACT: We aimed to retrieve the vital status of patients lost to follow-up (LFU), with no further visits for at least 12 months, for the 34,835 patients in the Agence Nationale de Recherche sur le SIDA CO4 French Hospital Database on HIV (ANRS CO4 FHDH) seen in 1999 and to examine how loss to follow-up might influence estimates of survival and the impact of delayed access to care (DAC) on survival.
The status of LFU patients was established by using the mid-2006 update of the FHDH in which their status 12 months after loss to follow-up was added when available and by matching with the Mortalité 2000-Epidemiological Centre for Medical Causes of Death (CépiDc) database, which included HIV-infected patients dying in 2000. We compared Kaplan-Meier and hazard ratio (HR) estimates before and after correction for the status of LFU patients.
In the mid-2006 updated FHDH, of the patients seen in 1999, 7.5% were LFU: of these, 2.1% later returned for follow-up, with a median time without follow-up in an FHDH centre of 3.5 years, and 5.4% had no further FHDH visits whatsoever, of whom 29.8% died according to Mortalité 2000-CépiDc. After correction, the estimated 1-year survival rates following enrolment in 1999 differed between the original and updated analyses (97.1 vs. 95.9%, respectively; P=0.017); the estimates of mortality HRs associated with DAC did not differ during the first 6 months, but did differ for the 6-18-month period.
Among LFU patients, 28.1% returned to follow-up after several years and at least 21.4% died, which led to a slight overestimation of both survival and the impact of DAC on survival.
HIV Medicine 02/2009; 10(4):236-45. · 3.01 Impact Factor
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ABSTRACT: Non-acquired immune-deficiency syndrome (AIDS) defining malignancies (especially lung cancer) and bacterial infections as well as cardiovascular diseases now account for almost one third of deaths and morbid events in treated patients infected by the Human Immunodeficiency Virus (HIV). Tobacco smoking is a major modifiable risk factor of these emergent conditions and almost half of these patients are regular smokers in resource-rich countries.
To estimate the effect of HIV infection characteristics on smoking cessation attempts among HIV-infected smokers.
All smokers of the ANRS CO3 Aquitaine Cohort with at least two visits between 2000 and 2005 were included in this analysis. The probability of smoking cessation attempts was estimated using survival analyses for recurrent events (frailty model). Covariates were CD4 cell count, gender, age, HIV transmission categories, duration since HIV-diagnosis, AIDS stage, antiretroviral therapy, and cardiovascular history.
Among 2223 smokers, 743 attempted to quit smoking at least once. The incidence of smoking cessation attempt was lower among patients infected through injection drug use (IDU) and was higher among patients aged 50 or older (HR=1.4), those with a known duration of HIV infection >15 years (HR=1.5), and those who had already tried to quit smoking once (HR=4.2) or more (HR=5.8).
Traditional characteristics associated with smoking cessation attempts are the most important to explain smoking cessation attempts in HIV-infected patients. These results indicate that strategies successfully implemented in other populations should be reinforced to fit the needs of HIV-infected patients.
Current HIV research 02/2009; 8(3):212-7. · 1.98 Impact Factor
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ABSTRACT: Whether pregnancy has an impact on the evolution of CD4 cell counts in women treated with highly potent antiretrovirals before conception remains largely unknown.
Among patients enrolled in the ANRS CO8 (APROCO/COPILOTE) cohort, we selected all women aged between 18 and 50 years at initiation of combination antiretroviral therapy (cART). Slopes of CD4 cell counts during follow-up were estimated using mixed longitudinal models with time-dependent indicators for pregnancy and delivery.
Of the 260 selected HIV-infected women, a pregnancy occurred in 39 women in a median follow-up time of 66 months. Women who became pregnant had higher CD4 cell count at baseline but this difference progressively lessened during follow-up because they had a slower increase than women who did not become pregnant. The estimated slope of CD4 cell count decreased significantly from +2.3 cells/muL/month before pregnancy and in women who did not become pregnant to -0.04 cells/microL/month after delivery (P=0.0003).
A significant increase in CD4 cell count may be preferable before pregnancy in women treated with cART, in order to overcome the evolution observed after pregnancy.
HIV Medicine 10/2008; 9(10):897-900. · 3.01 Impact Factor
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ABSTRACT: We investigated the in vitro phenotypic susceptibility of HIV-2 isolates from integrase inhibitor (INI)-naive patients to INIs and its relation to HIV-2 integrase gene polymorphism.
We determined the phenotypic susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values were compared with those for HIV-1 reference strains. HIV-2 integrase gene polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the French HIV-2 cohort.
Median raltegravir and elvitegravir IC(50) values for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38% of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the HHCC and RKK motifs were fully conserved, at the same genomic positions as described in HIV-1. In subtype B isolates, the total length of the integrase gene varied, owing to the presence of stop codons at positions 288, 294, 297 and 302. Fourteen of the positions associated with substitutions conferring INI resistance in HIV-1 were polymorphic in HIV-2.
Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.
Journal of Antimicrobial Chemotherapy 09/2008; 62(5):914-20. · 5.07 Impact Factor
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ABSTRACT: The objective of this investigation was to describe systems for the epidemiological surveillance of congenital toxoplasmosis implemented in European countries. In September 2004, a questionnaire, adapted from the evaluation criteria published by the United States Centers for Disease Control and Prevention, was sent to a panel of national correspondents in 35 countries in the European geographical area with knowledge of the epidemiological surveillance systems implemented in their countries. Where necessary, we updated the information until July 2007. Responses were received from 28 countries. Some 16 countries reported routine surveillance for toxoplasmosis. In 12 countries (Bulgaria, Cyprus, Czech Republic, England and Wales, Estonia, Ireland, Latvia, Lithuania, Malta, Poland, Scotland and Slovakia), surveillance was designed to detect only symptomatic toxoplasmosis, whether congenital or not. Four countries reported surveillance of congenital toxoplasmosis, on a regional basis in Italy and on a national basis in Denmark, France and Germany. In conclusion, epidemiological surveillance of congenital toxoplasmosis needs to be improved in order to determine the true burden of disease and to assess the effectiveness of and the need for existing prevention programmes.
Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 05/2008; 13(15). · 6.15 Impact Factor
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ABSTRACT: The aim of the study was to characterize the causes, trends and determinants of severe morbidity in a large cohort of HIV-infected patients between 2000 and 2004.
Severe morbid events were defined as medical events associated with hospitalization or death. Epidemiological and biological data were recorded at the time of the morbid event. Trends were estimated using Poisson regression.
Among 3863 individuals followed between 2000 and 2004, 1186 experienced one or more severe events, resulting in 1854 hospitalizations or deaths. The severe events recorded included bacterial infections (21%), AIDS events (20%), psychiatric events (10%), cardiovascular events (9%), digestive events including cirrhosis (7%), viral infections (6%) and non-AIDS cancers (5%). Between 2000 and 2004, the incidence rate of AIDS events decreased from 60 to 20 per 1000 person-years, that of bacterial infections decreased from 45 to 24 per 1000 person-years, and that of psychiatric events decreased from 26 to 14 per 1000 person-years (all P<0.01), whereas the incidences of cardiovascular events and of non-AIDS cancers remained stable at 14 and 10 per 1000 person-years, on average, respectively.
Severe morbidity has shifted from AIDS-related to non-AIDS-related events during the course of HIV infection in developed countries. Limiting endpoints to AIDS events and death is insufficient to describe HIV disease progression in the era of combination antiretroviral therapy.
HIV Medicine 12/2007; 8(8):547-54. · 3.01 Impact Factor
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ABSTRACT: The aim of this 4-year, observational, single-center study was to identify prognostic factors and evaluate the need for intensive care in cases of bacterial meningitis. During the study period, 60 cases of adult bacterial meningitis were identified. Fifty-one patients were transferred to the intensive care unit at various times during their hospital stay. In the multivariate analysis, factors significantly associated with the need for mechanical ventilation and/or vasopressive drugs included comorbidity and a Glasgow coma score of less than 12 at hour 6 following presentation. The results indicate patients with a decreased level of consciousness, neurological deficit or comorbidity should be admitted to the intensive care unit at an early stage of illness. When patients lack these criteria 6 h following presentation, admission to the medical ward is reasonable.
European Journal of Clinical Microbiology 11/2007; 26(10):743-6. · 2.86 Impact Factor
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ABSTRACT: When the sensitivity of an assay used to quantify a marker is poor, some of the values are below the detection limit resulting in left-censoring. Analysis of such data requires appropriate statistical techniques. In this study, we aimed at comparing various methods used to deal with left-censored outcome in regression analysis.
The application was a real study evaluating the performance of procalcitonin for the diagnosis of bacterial infections among elderly patients. Among 85 patients, eleven had a procalcitonin value below the detection limit. A simulation study was then performed with data sampled according to a Gaussian distribution with parameters estimated on observed data. Various levels of left-censoring were simulated (13, 25 and 50%). A linear regression model was used to explain procalcitonin variations according to another marker, C reactive protein. To handle left-censoring, several methods were used: complete case analysis, simple imputation and multiple imputation methods, and parametric modelling. In the simulation study, estimations according to different methods were compared in terms of bias and mean square error according to each left-censoring level. Estimations obtained with real data were also compared according to the methods used. All analyses were implemented using SAS software.
In the simulation study, parametric modelling using maximum likelihood showed best performances whatever the level of censoring. On the other hand, methods using complete cases and simple imputation by the detection limit were highly skewed. On observed data, estimations of the slope varied slightly according to the methods. However the p-values (Wald test) of beta=0 varied from 0.0001 to 0.13 leading to different decisions according to the method used.
Left-censoring handling in data analysis requires special attention, as different methods may yield results leading to different conclusions.
Revue d Épidémiologie et de Santé Publique 07/2007; 55(3):213-20. · 0.78 Impact Factor
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ABSTRACT: The increase in CD4 count may reach a plateau after some duration of virological response to highly active antiretroviral therapy (HAART).
A total of 1281 HIV-infected patients initiating HAART were enrolled in the AntiPROtease (APROCO) cohort. We investigated determinants of increase in CD4 count using longitudinal mixed models in patients who maintained a plasma HIV RNA <500 HIV-1 RNA copies/mL.
A total of 870 patients had a virological response at month 4. The median follow-up time was 57 months. Mean estimated increases in CD4 count in patients with persistent virological response were 29.9 cells/muL/month before month 4, 6.4 cells/microL/month between months 4 and 36, and 0.7 cells/microL/month (not significantly different from 0) after month 36. Three factors were associated with a significantly positive CD4 count slope after month 36: male gender (+0.9), no history of antiretroviral therapy at baseline (+1.7) and baseline CD4 count <100 cells/microL (+2.6). In patients who maintained a virological response after 5 years of HAART, a CD4 count >500 cells/microL was achieved in 83% of those with a baseline CD4 count >or=200 cells/microL and in 45% of those with a baseline CD4 count <200 cells/microL.
The increase in CD4 count reaches a plateau after 3 years of virological response. Even if patients initiating HAART with low CD4 counts still show a CD4 count increase after 3 years, it remains insufficient to overcome immune deficiency in all patients.
HIV Medicine 05/2007; 8(3):156-63. · 3.01 Impact Factor
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C Brunet-François,
A Taieb,
B Masquelier,
V Le Moing,
C Lewden,
P Dellamonica,
L Cuzin,
C Allavena,
B Spire, G Chêne,
F Raffi
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ABSTRACT: This study was made to determine the immunovirological outcome and tolerance to lopinavir/ritonavir (LPV/r) in HIV-infected protease inhibitors-experienced patients with long-term virological failure.
Prospective follow-up was implemented for the French cohort ANRS CO8 Aproco-Copilote of 121 patients starting an LPV/r-containing regimen after a median duration of virological failure of 30.6 months. At baseline the median HIV-RNA plasma level was 4.1 log(10) copies/ml and the median CD4 cell count was 273/mm(3).
On initiation of LPV/r, these patients were heavily pre-treated: 62% had received at least 4 NRTI, 65% at least 1 NNRTI, and 33% at least 3 PI. On prescription of LPV/r, the associated antiretroviral regimen was: no drug to which patients were previously naïve in 49 cases (40%), at least one new drug in 72 cases: 1 NRTI (n=42), 2 NRTI (n=22), 1 NNRTI (n=10), at least one new PI (n=6), enfuvirtide (n=2). The median HIV-RNA level was 2 log(10) copies/ml at M4 and M12, 1.7 log(10) copies/ml at M24 with respectively 74, 71 and 85% of patients achieving plasma HIV-RNA below 2.7 log(10) copies/ml. The median CD4 cell count was 385 and 429/mm(3) at M12 and M24 respectively. Among patients with genotypic testing at the time of LPV/r initiation, Ninety-five percent had at the most 5 protease mutations known to reduce LPV/r susceptibility. Thirty serious adverse events were reported but only 6 were related to LPV/r.
The use of LPV/r in HIV-infected patients failing multiple antiretroviral regimens provided a potent and durable immunovirological response.
Médecine et Maladies Infectieuses 04/2007; 37(3):172-7. · 0.72 Impact Factor
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ABSTRACT: We estimated the number of deaths in France for the year 2000 in HIV-infected adults using three sources. The sources were (1) the 'Mortalité 2000' survey (M2000): 964 deaths were documented by 185 hospital wards involved in HIV management; (2) 1288 death certificates with a mention of HIV infection (INSERM-CepiDc) and (3) the French hospital database on HIV infection (FHDH) identified 654 deaths. The capture-recapture method was used with log-linear modelling. Overall 1559 deaths were observed. Estimation of the number of deaths in France was 1699 (95% CI 1671-1727). The completeness of M2000, CepiDc and FHDH were 55%, 76% and 38% respectively. Diversification of diseases and of causes of death in HIV-infected adults may explain: (1) the diversification of physicians involved in their management and incomplete coverage of M2000 and FHDH, and (2) why HIV infection was not mentioned in all death certificates.
Epidemiology and Infection 01/2007; 134(6):1345-52. · 2.84 Impact Factor
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ABSTRACT: To describe the incidence and risk factors of bacterial pneumonia occurring in patients treated with antiretrovirals.
In the ongoing APROCO (Anti-proteases) cohort, 1281 patients at the initiation of a protease inhibitor (PI)-containing antiretroviral regimen were enrolled from 1997-1999. All events requiring hospitalization during follow up are recorded. Of these, bacterial pneumonia was defined as the occurrence of a new pulmonary infiltrate with fever and either evidence of a bacteriological cause (definite cases) or favourable outcome with antimicrobial therapy (presumptive cases). Risk factors of bacterial pneumonia were studied using survival analyses.
During a median follow up of 43 months, 29 patients had at least one episode of bacterial pneumonia, giving an incidence of 0.8/100 patient years. The 11 definite cases were attributable to Streptococcus pneumoniae (n=9), Legionella pneumophila (n=1) and Haemophilus influenzae (n=1). In multivariate analysis, bacterial pneumonia was significantly more frequent in older patients, injecting drug users, patients having a CD4 cell count>500 cells/microL at baseline and patients who initiated PI therapy with nonboosted saquinavir. It was significantly less frequent in nonsmokers. The occurrence of bacterial pneumonia was also associated with lower self-reported adherence to antiretroviral therapy and to higher plasma HIV-1 RNA levels during follow-up.
Bacterial pneumonia occurs rarely in patients treated with a PI-containing regimen and may be associated with virological failure.
HIV Medicine 05/2006; 7(4):261-7. · 3.01 Impact Factor
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ABSTRACT: To provide up-to-date and covariate-specific estimates on tobacco smoking prevalence in a representative cohort of French human immunodeficiency virus (HIV) 1 infected patients in 2002.
We conducted a cross-sectional analysis of the Aquitaine Cohort of HIV-infected patients. A logistic regression model was used to estimate associations between regular tobacco smoking and sex, age, HIV transmission categories, duration and immuno-virological status of HIV infection and duration of antiretroviral therapy. Smoking prevalence estimates were compared with the general French population values after stratification on age and sex.
Among 2036 patients included in the analysis, 51% were regular smokers (95%CI 49-53). Smoking prevalence was significantly higher with younger age (OR 1.7 among those < or = 45 years of age), among injecting drug users (OR 4.3), among those whose infection was not controlled (OR 1.2) and those whose HIV infection had been diagnosed for > or = 5 years (OR 1.5). The main difference with the general population was the peak smoking prevalence among HIV-positive patients infected through injecting drug use.
HIV-infected patients are highly exposed to tobacco smoking, which is implicated in multiple conditions occurring in the course of HIV infection. Adapted smoking cessation programmes should become one of the priorities of the medical care of HIV-infected individuals.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 04/2006; 10(4):378-83. · 2.73 Impact Factor