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1.
Br J Haematol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468517

RESUMO

The prognostic value of cell of origin (COO) classification and BCL2 expression is not well established in diffuse large B-cell lymphoma (DLBCL) patients with human immunodeficiency virus (HIV) infection in the recent era. Phenotypic patterns were determined by immunohistochemistry (IHC) of pathological samples from patients with HIV-associated DLBCL prospectively enrolled in the French AIDS and Viral Hepatitis CO16 Lymphovir cohort between 2008 and 2015. Molecular subgroup classification into germinal centre B-cell (GCB) and non-GCB subtypes was determined using the Hans algorithm. Among 52 samples of systemic DLBCL subjected to centralized pathological analysis, 25 of the 42 tested for BCL2 expression were positive. Samples were further classified into GCB (n = 19) and non-GCB (n = 16) subtypes and 17 remained unclassified. In multivariable analysis, BCL2 expression was an independent pejorative prognostic biomarker [4-year progression-free survival (PFS): 52% for BCL2+ vs. 88% for BCL2- , P = 0·02] and tended to reduce 4-year overall survival (OS) (63% for BCL2+ vs. 88% for BCL2- , P = 0·06). The difference between CGB and non-GCB subtypes on PFS and OS did not reach significance (4-year PFS: 79% for GCB vs. 53% for non-GCB, P = 0·24 and 4-year OS: 78% for GCB vs. 69% for non-GCB, P = 0·34). BCL2 expression determined by IHC is an independent pejorative prognostic biomarker in HIV-associated DLBCL in the recent era. This supports the investigation of new therapeutic strategies in patients with BCL2 expression.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31384941

RESUMO

OBJECTIVES: We assessed virological outcomes of darunavir use in France from 2012 to 2016, in three groups of people living with HIV (PLHIV): (i) antiretroviral (ARV)-naive PLHIV; (ii) ARV-experienced PLHIV switching to darunavir while failing therapy; and (iii) ARV-experienced PLHIV switching to darunavir while virologically controlled. METHODS: Virological success (VS) was defined as a plasma HIV-1 viral load (VL) <50 copies/mL and virological failure (VF) as two consecutive VL >50 copies/mL or one VL >50 copies/mL followed by a treatment switch prior to the next VL measurement. The cumulative incidence of VS was assessed considering darunavir discontinuation, loss to follow-up and death as competing risks, while estimates of cumulative incidence of VF accounted for loss to follow-up and death. RESULTS: Among the 3235 ARV-naive PLHIV initiating darunavir, the 4 year cumulative incidence of VS was 80.9% and was associated with lower VL and higher CD4 cell counts. Among the 3485 ARV-experienced PLHIV switching to darunavir while failing therapy, the 4 year cumulative incidence of VS was 82.2% and was associated with lower VL. Among the 3005 ARV-experienced PLHIV switching to darunavir while virologically controlled, the 4 year cumulative incidence of VF was 12.6%. The risk of VF was higher with darunavir monotherapy [subdistribution hazard ratio (sHR)=1.67, 95% CI 1.15-2.42] while no difference was observed with dual therapy (sHR = 1.00, 95% CI 0.71-1.42) relative to triple therapy or more. CONCLUSIONS: Darunavir-containing regimens yielded similarly high rates of viral suppression in PLHIV whether they were ARV naive or ARV experienced switching to darunavir while failing therapy, or of maintaining VS in ARV-experienced PLHIV switching to darunavir while virologically controlled.

3.
J Int AIDS Soc ; 22(8): e25371, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31424626

RESUMO

INTRODUCTION: Increasing our knowledge on geographic areas and key populations most affected by HIV is essential to improve prevention and care and to ensure a more focused HIV response. Here, we estimated the prevalence of undiagnosed HIV infections in Belgium and its distribution across geographic areas and exposure groups. METHODS: We used surveillance data on newly diagnosed HIV cases and a previously developed back-calculation model to estimate number and prevalence rates (per 10000) of undiagnosed HIV infections by exposure group at national and subnational levels. Belgium consists of three regions: Flanders, Brussels-Capital Region and Wallonia. We produced estimates for Brussels-Capital Region and Wallonia. For Flanders, we produced estimates for two sub-regional areas: the province of Antwerp and the other provinces, because Antwerp is the second largest city after Brussels. Population sizes were determined using data from the Belgian Statistical Office and surveys on sexual behaviour and drug use. RESULTS: In Belgium, in 2015, an estimated 2818 (95% confidence interval: 2494 to 3208) individuals were living with undiagnosed HIV, that is, 15% of individuals living with HIV. The Brussels-Capital Region and the province of Antwerp, which host the two biggest cities, accounted for ~60% of the undiagnosed infections, and had the highest undiagnosed prevalence rates per 10000: 12.0 (9.4 to 15.3) and 7.4 (5.6 to 9.8) respectively. Individuals with foreign nationality accounted for 56% of the total number of undiagnosed infections, and were the most affected populations in all areas in terms of undiagnosed prevalence rates. Specifically, men who have sex with men (MSM) with non-European nationality were the most affected population in the province of Antwerp (853.4 (408.2 to 1641.9) undiagnosed infections per 10000), the Brussels-Capital Region (543.9 (289.1 to 1019.1)), and the other provinces of Flanders (691.7 (235.5 to 1442.2)), while in Wallonia, it was heterosexual women with Sub-Saharan African nationality (132.2 (90.6 to 178.5)). CONCLUSIONS: Geographic areas hosting the biggest cities in Belgium accounted for the vast majority of undiagnosed HIV infections and individuals with foreign nationality were the most affected, especially MSM with non-European nationality. This should be accounted for when tailoring prevention and testing programs. Furthermore, MSM with foreign nationality require more attention in Belgium, and certainly more generally in Europe.

4.
J Antimicrob Chemother ; 74(9): 2742-2751, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269208

RESUMO

BACKGROUND: Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. METHODS: The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate ≥95%, with a power of 80% and a 5% type-1 error. RESULTS: One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CI = 95.6%-99.9%) at week 48 and 98.7% (95% CI = 95.0%-99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CI = 90.5%-97.5%) at week 48 and 92.7% (95% CI = 87.5%-95.8%) at week 96. Over 96 weeks, lipid fractions improved (P < 0.001), CD4/CD8 ratio increased, IFNγ-induced protein 10 (IP-10) decreased (-8.1%), soluble CD14 decreased (-27%, P < 0.001) bone mineral density improved and BMI increased. CONCLUSIONS: Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.

5.
Clin Infect Dis ; 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31351441

RESUMO

The French epidemics of iatrogenic CJD after GH treatment provides an opportunity to understand factors governing the inter-human transmission of prions. The present analysis relying on truncated Weibull distribution supports a relationship between host genetics, dose of the at-risk GH, age at treatment onset and duration of the incubation period.

6.
Am J Transplant ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31206243

RESUMO

We compared access to a kidney transplantation (KT) waiting list (WL) and to KT between people living with HIV (PLHIV) and HIV-uninfected controls. Using the REIN (the national Renal Epidemiology and Information Network registry), we included all PLHIV initiating dialysis in France throughout 2006-2010 and HIV-uninfected controls matched for age, sex, year of dialysis initiation, and the existence of a diabetic nephropathy. Patients were prospectively followed until December 2015. We used a competitive risk approach to assess the cumulative incidence of enrollment on WL and of KT, with death as a competing event (subdistribution hazard ratio adjusted on comorbidities, asdHR). There were 255 PLHIV in the REIN (median age 47 years) of whom 180 (71%) were also found in the French Hospital Database on HIV (FHDH-ANRS CO4) including 126 (70%) known to be on antiretroviral therapy with HIV viral suppression (VS). Five years after dialysis initiation, 65%, and 76%, of treated PLHIV with VS, and of HIV-uninfected controls were enrolled on a WL (asdHR 0.68; 95% CI 0.50-0.91). Access to KT was also less frequent and delayed for treated PLHIV with VS (asdHR 0.75, 95% CI, 0.52-1.10). PLHIV continue to face difficulties to access KT.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31071216

RESUMO

BACKGROUND: The incidence of chronic kidney disease (CKD) is 10 times higher in human immunodeficiency virus (HIV)-infected patients than in the general population. We explored the prevalence and determinants of proximal tubular dysfunction (PTD) in HIV-infected individuals, and assessed the impact of the tubulopathy on the estimated glomerular filtration rate (eGFR) outcome. METHODS: A cohort study was performed on 694 outpatients followed in a French centre to analyse the prevalence of PTD, the diagnosis performance of screening tools and the associated factors. eGFR was prospectively evaluated to analyse the predictive value of the tubulopathy on eGFR decrease. RESULTS: At inclusion, 14% of the patients presented with PTD and 5% with CKD. No individual tubular marker, including non-glomerular proteinuria, glycosuria dipstick or hypophosphataemia, registered sufficient performance to identify PTD. We found a significant interaction between tenofovir disoproxil fumarate exposure and ethnicity (P = 0.03) for tubulopathy risk. Tenofovir disoproxil fumarate exposure was associated with PTD in non-Africans [adjusted odds ratio (aOR) = 4.71, P < 10-3], but not in patients of sub-Saharan African origin (aOR = 1.17, P = 0.73). Among the 601 patients followed during a median of 4.3 years, 13% experienced an accelerated eGFR decline. Unlike microalbuminuria and glomerular proteinuria, tubulopathy was not associated with accelerated eGFR decline. CONCLUSION: PTD is not rare in HIV-infected individuals but is less frequent in sub-Saharan African patients and is associated with tenofovir disoproxil fumarate exposure only in non-Africans. Its diagnosis requires multiple biochemical testing and it is not associated with an accelerated eGFR decline.

8.
Am J Epidemiol ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063192

RESUMO

Effect estimates from randomized trials and observational studies may not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a three-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocol (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive to the human immunodeficiency virus from the START randomized trial and the observational HIV-CAUSAL Collaboration.

9.
J Acquir Immune Defic Syndr ; 81(5): 547-551, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31107300

RESUMO

BACKGROUND: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD. METHODS: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group. RESULTS: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class. CONCLUSION: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.

10.
AIDS ; 33(6): 993-1000, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30946153

RESUMO

OBJECTIVES: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis of HIV-related classical Hodgkin lymphoma (HIV-cHL). The utility of EBV molecular and serological biomarkers has scarcely been examined in HIV-cHL in the recent combined antiretroviral therapy (cART) era. DESIGN: We evaluated EBV DNA load and a panel of EBV antibodies in HIV-cHL patients prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015. METHODS: Pretreatment whole blood, plasma EBV DNA load and serological profiles were analysed in 63 HIV-infected patients diagnosed with cHL. For the 42 patients with available material, comparisons were performed between values at diagnosis and 6 months after the initiation of chemotherapy. RESULTS: Pretreatment whole blood and plasma EBV DNA loads were positive in 84 and 59% of HIV-cHL patients, respectively. Two-year progression-free survival estimates did not differ between the patients with pretreatment whole blood (n = 53) or plasma (n = 37) EBV DNA(+) and the patients with pretreatment whole blood (n = 10) or plasma (n = 26) EBV DNA(-) (92 vs. 80% or 89 vs. 92%, P = 0.36 and 0.47, respectively). At diagnosis, 47% of patients harboured an EBV reactivation serological profile. Following chemotherapy, whole blood and plasma EBV DNA levels significantly declined from medians of 1570 [interquartile range, 230-3760) and 73 (0-320) copies/ml to 690 (0-1830) and 0 (0-0) copies/ml, respectively (P = 0.02 and P < 0.0001, respectively]. Anti-EBV IgG antibody level significantly dropped at 6-month follow-up (P = 0.004). CONCLUSION: Whole blood and plasma EBV DNA loads do not constitute prognostic markers in HIV-cHL patients in the modern cART era.

11.
Pharmacotherapy ; 39(4): 514-520, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30815916

RESUMO

STUDY OBJECTIVE: The ANRS163-ETRAL study showed that etravirine 200 mg/raltegravir 400 mg twice-daily dual therapy was highly effective in the treatment of human immunodeficiency virus (HIV)-infected patients older than 45 years, with virologic and therapeutic success rates at week 48 of 99.4% and 94.5%, respectively. The objective of this study was to determine whether a clinically significant pharmacokinetic interaction between etravirine and raltegravir exists by assessing steady-state total and unbound etravirine, raltegravir, and inactive raltegravir-glucuronide concentrations 12 hours after last intake (C12h ) in blood plasma (BP) and seminal plasma (SP). DESIGN: Pharmacokinetic analysis of data from the ANRS163-ETRAL study. PATIENTS: One hundred forty-six HIV-1-infected patients (of the 165 patients included in the ANRS-163 ETRAL study) who were receiving etravirine 200 mg and raltegravir 400 mg twice daily. MEASUREMENTS AND MAIN RESULTS: Blood was collected from all 146 patients at weeks 2-4, 12, 24, and 48, and semen was collected from 21 patients at week 48. The extent of BP and SP protein binding was determined by using ultrafiltration assay. Total and unbound etravirine, raltegravir, and raltegravir-glucuronide C12h were determined by ultra high performance liquid chromatography coupled with tandem mass spectrometry and interpreted by using the in vitro calculated protein-bound 95% inhibitory concentration (PBIC95 ) for wild-type (WT) HIV: etravirine (116 ng/ml) and raltegravir (15 ng/ml). Median (interquartile range [IQR]) total BP etravirine C12h (536 ng/ml [376-719]) and raltegravir (278 ng/ml [97-690]) were adequate in 99% and 96% of patients, respectively. Median (IQR) SP:BP C12h ratio and BP unbound fraction were etravirine 0.3 (0.2-0.5) and < 1%, respectively, raltegravir 1.8 (1.3-3.3) and 12%, respectively, and raltegravir-glucuronide 12.0 (6.5-17.7) and > 99%, respectively. The BP raltegravir metabolic ratio (raltegravir glucuronide:raltegravir ratio) was 1.7, suggesting only weak induction of raltegravir glucuronidation by etravirine. Only three patients had etravirine and raltegravir C12h < PBIC95 simultaneously. CONCLUSION: No clinically significant pharmacokinetic interaction between etravirine and raltegravir was detected. Total etravirine and raltegravir BP concentrations were adequate in most patients, favoring virologic efficacy and confirming good treatment adherence (> 95%), despite twice-daily administration. The long half-life of etravirine and higher unbound fraction SP of raltegravir (57%) ensured adequate concentrations of dual therapy in genital compartments. Our results indicate that etravirine and raltegravir have good, complementary pharmacokinetic profiles, suggesting that they could be used in a dual-treatment strategy.

12.
Stat Med ; 38(13): 2428-2446, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30883859

RESUMO

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/µl compared with 500 cells/µl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

13.
PLoS One ; 14(1): e0210253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650119

RESUMO

We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/µL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30639161

RESUMO

OBJECTIVE: Existing staging models have not been fully validated. Thus, after classifying patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), we explored the validity of this staging model and its stability after one-year of follow-up. METHOD: Using unsupervised machine-learning algorithm, we classified 770 outpatients into 5 clinical stages, the highest being the most severe. Analyses of (co)variance were performed to compare each stage in regard to socio-demographics factors, clinical characteristics, co-morbidities, ongoing treatment and neuropsychological profiles. RESULTS: The precision of clinical staging can be improved by sub-dividing intermediate stages (II and III). Clinical validators of class IV include the presence of concomitant major depressive episode (42.6% in stage IV versus 3.4% in stage IIa), more severe cognitive profile, lower adherence to medication and prescription of >3 psychotropic medications. Follow-up at one-year showed good stability of each stage. CONCLUSION: Clinical staging in schizophrenia could be improved by adding clinical elements such as mood symptoms and cognition to severity, relapses and global functioning. In terms of therapeutic strategies, attention needs to be paid on the factors associated with the more stages of schizophrenia such as treatment of comorbid depression, reduction of the number of concomitant psychotropic medications, improvement of treatment adherence, and prescription of cognitive remediation.

15.
J Acquir Immune Defic Syndr ; 80(3): 292-300, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531492

RESUMO

BACKGROUND: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. METHODS: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. RESULTS: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm. DISCUSSION: Starting ART with a CD4 cell count of ≥500 cells/mm makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.

16.
J Acquir Immune Defic Syndr ; 80(4): e86-e94, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30570529

RESUMO

BACKGROUND: HIV-monoinfected individuals are at high risk of nonalcoholic fatty liver disease. Noninvasive tests of steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis have been poorly assessed in this population. Using liver biopsy (LB) as a reference, we assessed the accuracy of noninvasive methods for their respective diagnosis: magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF), FibroScan/controlled attenuation parameter (CAP), and biochemical tests. METHODS: We enrolled antiretroviral therapy-controlled participants with persistently elevated transaminases and/or metabolic syndrome, and/or lipodystrophy. All had hepatic MRI-PDFF, FibroScan/CAP, FibroTest/NashTest/SteatoTest, APRI, FIB-4, and nonalcoholic fatty liver disease-fibrosis score. A LB was indicated if suspected significant fibrosis (FibroScan ≥7.1 kPa and/or FibroTest ≥0.49). Performance was considered as good if area under a receiver operating characteristic curves (AUROCs) was >0.80. RESULTS: Among the 140 patients with suspected significant fibrosis out of the 402 eligible patients, 49 had had a LB: median age of 54 years (53-65), body mass index: 26 kg/m (24-30), steatosis in 37 (76%), NASH in 23 (47%), and fibrosis in 31 (63%) patients [F2: 7 (14%); F3: 6 (12%); and F4: 2 (4%)]. Regarding steatosis, MRI-PDFF had excellent and CAP good performances with AUROCs at 0.98 (95% confidence interval: 0.96 to 1.00) and 0.88 (0.76 to 0.99), respectively, whereas the AUROCs of SteatoTest was 0.68 (0.51 to 0.85). Regarding fibrosis (≥F2), APRI and FIB-4 had good performance with AUROCs at 0.86 (0.74 to 0.98) and 0.81 (0.67 to 0.95). By contrast, FibroScan and FibroTest had poor AUROCs [0.61 (0.43 to 0.79) and 0.61 (0.44 to 0.78)], with very low specificity. Regarding NASH, alanine aminotransferase ≥36 IU/L had good performance with AUROCs of 0.83 (0.71 to 0.94), whereas the NashTest had an AUROC of 0.60 (0.44 to 0.76). CONCLUSIONS: In HIV-monoinfected patients, MRI-PDFF and FibroScan/CAP are highly accurate for the diagnosis of steatosis. The alanine aminotransferase level and APRI should be considered for the detection of NASH and fibrosis.

17.
AIDS ; 33(1): 133-143, 2019 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-30289806

RESUMO

OBJECTIVE: HIV cohorts are an important source of clinical data for informing public health policies and programmes. However, the generalizability of cohort findings to the wider population of people diagnosed with HIV in each country remains unclear. In this work, we assessed the representativeness of six large national HIV cohorts within Europe. DESIGN AND METHODS: Individual-level cohort data were provided from national cohorts in France, Germany, Greece, Italy, Spain and the United Kingdom. Analysis focused on new HIV diagnoses reported to The European Surveillance System (TESSy) during three time periods (2000-2004, 2005-2009 and 2010-2013), to allow for temporal changes. Cohort and TESSy records were matched and compared by age, sex, transmission mode, region of origin and CD4 cell count at diagnosis. The probability of being included in each cohort given demographic characteristics was estimated and used to generate weights inversely proportional to the probability of being included. RESULTS: Participating cohorts were generally representative of the national HIV-diagnosed population submitted to TESSy. However, people who inject drugs, those born in a country other than that reporting the data, those with low CD4 cell counts at diagnosis, and those more than 55 years were generally underrepresented in the cohorts examined. CONCLUSION: These European cohorts capture a representative sample of the HIV-diagnosed populations in each country; however some groups may be underrepresented.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30422911

RESUMO

BACKGROUND: HIV-infected patients have lower bone mineral density and a higher incidence of fractures than the general population of the same age and sex. To assess the impact of antiretroviral drugs (ARV) exposure on the risk of osteoporotic fractures, we conducted a nested case-control study. METHODS: Cases were individuals enrolled while ARV-naive, with a first prospectively recorded fracture between 2000 and 2010. Controls were randomly selected after matching for sex, age (±3years), period of HIV diagnosis (<1997/≥1997) and clinical centre. The risk of fracture was analysed with conditional logistic regression models, using different ways to model ARV exposure. All exposure variables and potential confounders were included in multivariable models. RESULTS: Among 861 reviewed cases, 261 fractures were osteoporotic and 254 of cases were matched to at least one control (376 controls). The median year of fracture diagnosis was 2007 (IQR 2004-2009): 49% of patients had been exposed to tenofovir disoproxil fumarate (TDF) and 82% to protease inhibitors (PIs).After taking into account the transmission group, AIDS status, geographic origin, BMI, current smoking status, alcohol consumption, exposure to systemic glucocorticoids, and the period of enrolment, there was no association between the risk of fracture and exposure to TDF (OR for cumulative exposure: 1.04 [0.86-1.27], similar results for ever-exposed subjects), to NRTIs, or to PIs (OR for cumulative PI exposure: 1.02 [0.92-1.12]). CONCLUSION: We found no evidence of an excess risk of fracture following exposure to TDF or PIs. This has important implications for the debate concerning tenofovir alafenamide versus generic TDF.

19.
PLoS One ; 13(10): e0205385, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30379870

RESUMO

BACKGROUND: The influence of geographic origin on the risk of severe illness and death on cART has not been explored in European countries. METHOD: We studied antiretroviral-naïve heterosexual HIV-1-infected individuals enrolled in the FHDH-ANRS CO4 cohort in France who started cART between 2006 and 2011. Individuals originating from France (French natives), sub-Saharan Africa (SSA) and non-French West-Indies (NFW) were studied until 2012. Crude and adjusted rate ratios (aRR) of severe morbid events/deaths (AIDS-related and non-AIDS-related) were calculated using Poisson regression models stratified by sex, comparing each group of migrants to French natives. RESULTS: Among 2334 eligible men, 1379 (59.1%) originated from France, 838 (35.9%) from SSA and 117 (5.0%) from NFW. SSA male migrants had a higher aRR for non-AIDS infections, particularly bacterial infections (aRR 1.56 (95% CI 1.07-2.29), p = 0.0477), than French natives. Among 2596 eligible women, 1347 (51.9%) originated from France, 1131 (43.6%) from SSA, and 118 (4.5%) from NFW. SSA and NFW female migrants had a higher aRR for non-AIDS infections, particularly non-bacterial infections (respectively, 2.04 (1.18-3.53) and 7.87 (2.54-24.4), p = 0.0010), than French natives. We observed no other significant differences related to geographic origin as concerns the aRRs for AIDS-related infections or malignancies, or for other non-AIDS events/deaths such as cardiovascular disease, neurological/psychiatric disorders, non-AIDS malignancies and iatrogenic disorders, in either gender. CONCLUSION: Heterosexual migrants from SSA or NFW living in France have a higher risk of non-AIDS-defining infections than their French native counterparts. Special efforts are needed to prevent infectious diseases among HIV-infected migrants.

20.
AIDS ; 32(17): 2605-2614, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30289817

RESUMO

OBJECTIVE: To assess CD4 recovery after combined antiretroviral therapy (cART) initiation with sustained virologic control. DESIGN: Cohort study based on the French Hospital Database on HIV (FHDH-ANRS CO4). METHODS: We selected naive HIV-1-infected individuals initiating cART between 2006 and 2014 with CD4 cell counts less than 500 cells/µl who achieved virologic control, defined as two consecutive viral loads less than 50 copies/ml. We estimated the cumulative incidence of CD4 recovery at least 500 cells/µl and identified associated factors, considering 'virologic failure,' 'loss to follow-up' and 'death' as competing events. RESULTS: We analyzed 6050 individuals with a median follow-up of 14.2 months since virologic control. The cumulative incidence for CD4 recovery after 6 years of virologic control reached 69.7%. The main factor associated with CD4 recovery was the CD4 count at treatment initiation [subdistribution hazard ratio (sHR) 9.64, 95% confidence interval (95% CI) 8.12-11.43 for CD4 cell counts between 350 and 500 cells/µl compared with CD4 cell counts <100 cells/µl). A higher CD4/CD8 ratio at initiation was also independently associated with a higher probability of CD4 recovery [sHR 1.67; 95% CI 1.34-2.09] for a CD4/CD8 ratio ≥1.00 vs. < 0.30). Higher viral load at initiation was also associated with a higher probability of CD4 recovery, whereas time to viral suppression was not. CONCLUSION: After 6 years of sustained virologic control, a large majority of the population achieved CD4 recovery. A higher CD4 cell count at initiation was a strong predictor of CD4 recovery and, to a lesser extent, a higher CD4/CD8 ratio at initiation. These results confirm the necessity of early treatment.

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