[Show abstract][Hide abstract] ABSTRACT: The impact of hepatitis C virus (HCV)-related characteristics such as genotype, viral load or liver fibrosis on the chances of achieving sustained HIV suppression in coinfected patients is not fully documented. We examined the relationship between both HIV/HCV-related and sociobehavioural characteristics and HIV sustained viral suppression (SVS) in 897 patients included in the ANRS CO13 HEPAVIH cohort. The main outcome variable was HIV SVS, defined as at least two consecutive undetectable HIV viral loads. Among the 897 HIV/HCV-coinfected patients, 419 (47%) had received HCV therapy at least once, and 103 patients (25%) had experienced an HCV sustained virologic response (SVR). In multivariate analysis, older age [odds ratio (OR) 1.23 for each period of 5 years of age, 95% confidence interval (CI) 1.02-1.49; P = 0.03], a higher level of school education (OR 1.92, 95% CI 1.04-3.56; P = 0.04), good adherence to HIV therapy (OR 2.05, 95% CI 1.23-3.43; P = 0.006) and HCV SVR (OR 1.81, 95% CI 1.01-3.26; P = 0.04) remained significantly associated with HIV SVS. In contrast, triple nucleoside reverse transcriptase inhibitor (NRTI) regimens were associated with failure to achieve HIV SVS (OR 0.50, 95% CI 0.27-0.94; P = 0.03). Our results show that HCV SVR is associated with a higher likelihood of achieving HIV SVS. With the advent of direct-acting anti-HCV drugs, a marked increase in the rate of virologic response is observed in coinfected patients. So, further research is needed to determine whether suppression of HCV replication could be associated with a higher efficacy of antiretroviral therapy.
AIDS (London, England) 02/2014; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background & Aims
We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels.
Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (⩾3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N = 990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio.
After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR = 0.65; p = 0.04 and OR = 0.57; p = 0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p = 0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p = 0.003 for AST; p = 0.002 for ALT).
Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury.
Journal of Hepatology 01/2014; 60(1):46–53. · 9.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
TNF-alpha antagonists have changed the outcome of various chronic inflammatory diseases. Their use has spread widely and many patients receive those treatments for years. Previous reports found that the use of TNF-alpha antagonists may be associated with an increased risk of serious bacterial infections. We report 47 prospective bacteremia cases from the RATIO registry.
A national prospective study was conducted in France between 2004 and 2007 to collect severe bacterial infections in patients receiving TNF-alpha antagonists. All reported cases of bacteremia were validated by an expert committee.
Forty-seven bacteremic episodes were reported. Staphylococcus aureus represented the most frequent causative pathogen (40%) and was mostly associated with bones and/or joints infections (68%) and with a worse outcome compared to that observed with other bacterial pathogens.
Patients receiving TNF-alpha antagonists may develop bacteremia and S. aureus has to be included in the spectrum of the initial empiric antimicrobial therapy.
Journal of Infection 12/2013; 67(6):524–528. · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Differentiation marker, multifunctionality and magnitude analyses of specific-CD8(+) memory T cells are crucial to improve development of HIV vaccines designed to generate cell-mediated immunity. Therefore, we fully characterized the HIV-specific CD8(+) T cell responses induced in volunteers vaccinated with HIV lipopeptide vaccines for phenotypic markers, tetramer staining, cytokine secretion, and cytotoxic activities. The frequency of ex vivo CD8(+) T cells elicited by lipopeptide vaccines is very rare and central-memory phenotype and functions of these cells were been shown to be important in AIDS immunity. So, we expanded them using specific peptides to compare the memory T cell responses induced in volunteers by HIV vaccines with responses to influenza (FLU) or Epstein Barr virus (EBV). By analyzing the differentiation state of IFN-γ-secreting CD8(+) T cells, we found a CCR7(-)CD45RA(-)CD28(+int)/CD28(-) profile (>85%) belonging to a subset of intermediate-differentiated effector T cells for HIV, FLU, and EBV. We then assessed the quality of the response by measuring various T cell functions. The percentage of single IFN-γ T cell producers in response to HIV was 62% of the total of secreting T cells compared with 35% for FLU and EBV, dual and triple (IFN-γ/IL-2/CD107a) T cell producers could also be detected but at lower levels (8% compared with 37%). Finally, HIV-specific T cells secreted IFN-γ and TNF-α, but not the dual combination like FLU- and EBV-specific T cells. Thus, we found that the functional profile and magnitude of expanded HIV-specific CD8(+) T precursors were more limited than those of to FLU- and EBV-specific CD8(+) T cells. These data show that CD8(+) T cells induced by these HIV vaccines have a similar differentiation profile to FLU and EBV CD8(+) T cells, but that the vaccine potency to induce multifunctional T cells needs to be increased in order to improve vaccination strategies.
[Show abstract][Hide abstract] ABSTRACT: In HCV genotype 1-infected patients with HIV co-infection, tritherapy [HCV protease inhibitors (PIs) plus peg-interferon and ribavirin] has been shown to have an increased rate of sustained virological response. However, complex drug-to-drug interactions and tolerability issues remain a concern.
Under the auspices of four French scientific societies of medicine, a committee was charged of establishing guidelines on the use of first-generation HCV PIs in these patients. This scientific committee based its work on preliminary results from tritherapy clinical trials in co-infected patients and, since data on these patients are still scarce, on the statements already made by the French Association for the Study of the Liver (AFEF) on the use of tritherapy in HCV mono-infected patients, written in May 2011 and updated in 2012. Each AFEF guideline concerning HCV mono infection was examined in order to determine whether it could be used in the context of HIV/HCV coinfection.
These guidelines are addressed for the treatment of coinfected patients with various profiles, including treatment-naïve or patients with failure to previous bitherapy and mention those patients for whom tritherapy should start or those for whom it should be delayed. Preliminary results of triple therapy as well as factors associated to virological response are also discussed. Other issues include virological monitoring, clinical and virological criteria to stop therapy, practical treatment management, treatment adherence and the management of side effects and interactions with antiretroviral drugs. These guidelines were submitted for critical review to independent experts. This article is protected by copyright. All rights reserved.
Liver international: official journal of the International Association for the Study of the Liver 10/2013; · 3.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Combining noninvasive tests increases diagnostic accuracy for staging liver fibrosis in hepatitis C virus (HCV)-infected patients, but this strategy remains to be validated in HIV/HCV coinfection. We compared the performances of transient elastography (TE), Fibrotest (FT), the aspartate aminotransferase-to-platelet ratio index (APRI) and two algorithms combining TE and FT (Castera) or APRI and FT (SAFE) in HIV/HCV coinfection.
One hundred and sixteen HIV/HCV-coinfected patients (64% male; median age 44 years) enrolled in two French multicentre studies (the HEPAVIH cohort and FIBROSTIC) for whom TE, FT and APRI data were available were included in the study. Diagnostic accuracies for significant fibrosis (METAVIR F ≥ 2) and cirrhosis (F4) were evaluated by measuring the area under the receiver-operating characteristic curve (AUROC) and calculating percentages of correctly classified (CC) patients, taking liver biopsy as a reference.
For F ≥ 2, both TE and FT (AUROC = 0.87 and 0.85, respectively) had a better diagnostic performance than APRI (AUROC = 0.71; P < 0.005). Although the percentage of CC patients was significantly higher with Castera's algorithm than with SAFE (61.2% vs. 31.9%, respectively; P < 0.0001), this percentage was lower than that for TE (80.2%; P < 0.0001) or FT (73.3%; P < 0.0001) taken separately. For F4, TE (AUROC = 0.92) had a better performance than FT (AUROC = 0.78; P = 0.005) or APRI (AUROC = 0.73; P = 0.025). Although the percentage of CC patients was significantly higher with the SAFE algorithm than with Castera's (76.7% vs. 68.1%, respectively; P < 0.050), it was still lower than that for TE (85.3%; P < 0.033).
In HIV/HCV-coinfected patients, TE and FT have a similar diagnostic accuracy for significant fibrosis, whereas for cirrhosis TE has the best accuracy. The use of the SAFE and Castera algorithms does not seem to improve diagnostic performance.
[Show abstract][Hide abstract] ABSTRACT: Background. We examined trends in the incidence of the 3 AIDS-defining cancers (ADC) (Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) and cervical cancer) among HIV-infected patients relative to the general population between 1992 and 2009 in France, focusing on age at ADC diagnosis and on patients with controlled viral load and restored immunity on combined antiretroviral therapy (cART). Methods. Age- and sex- standardized incidence rates were estimated in patients enrolled in the French hospital database on HIV, and in the general population in France during 4 calendar periods (1992-1996, 1997-2000, 2001-2004, and 2005-2009). Standardized incidence ratios (SIR) were calculated for all periods and separately for patients on cART, with CD4 cell counts ≥500/mm(3) for at least 2 years and viral load ≤500 copies/ml. Results. Although the incidence of ADC fell significantly across the calendar periods, the risk remained constantly higher in HIV-infected patients than in the general population. In patients with restored immunity, the relative risk remained significantly elevated for KS [SIR= 35.4 (95% CI; 18.3-61.9)], and was similar to that of the general population for NHL [SIR= 1.0 (95% CI; 0.4-1.8)]. ADC were diagnosed at a younger age in HIV-infected patients, with a particularly marked difference for NHL (-11.3 years, p<0.0001). Conclusions. The incidence of all ADC continued to fall, including cervical cancer, in the cART period, but the risk remained higher than in the general population in 2005-2009. In patients with stably restored immunity, KS remained significantly more frequent than in the general population.
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT RATIONALE: We described legionellosis emergence during tumor necrosis factor (TNF)-α antagonist therapy. OBJECTIVE: Our objective here was to describe the incidence and risk factors of legionellosis associated with TNF-α antagonist use. METHODS: From February 1, 2004 to January 31, 2007, we prospectively collected all cases of legionellosis among French patients receiving TNF-α antagonists in the Research Axed on Tolerance of bIOtherapies (RATIO) national registry. We conducted an incidence study with the French population as a reference and a case-control analysis with 4 controls receiving TNF-α antagonists per case of legionellosis. RESULTS: Twenty-seven cases of legionellosis were reported. The overall annual incidence rate of legionellosis for patients receiving TNF-α antagonists, adjusted for age and sex, was 46.7 (95% confidence interval [95% CI] 0.0-125.7) per 100,000 patient-years. The overall standardized incidence ratio (SIR) was 13.1 (95% CI 9.0-19.1; p<0.0001) and was higher for patients receiving infliximab (SIR 15.3 [95% CI 8.5-27.6; p<0.0001]) or adalimumab (SIR 37.7 [95% CI 21.9-64.9, p<0.0001]) than etanercept (SIR 3.0 [95% CI 1.00-9.2, p=0.06]). In the case-control analysis, exposure to adalimumab (odds ratio [OR] 8.7 [95% CI 2.1-35.1]) or infliximab (OR 9.2 [95% CI 1.9-45.4]) versus etanercept was an independent risk factor for legionellosis. CONCLUSION: The incidence rate of legionellosis for patients receiving TNF-α antagonists is high and the risk is higher for patients receiving anti-TNF-α monoclonal antibodies than soluble TNF-receptor therapy. In case of pneumonia occurring during TNF-α antagonist therapy, specific urine antigen detection should be performed and antibiotic therapy should cover legionellosis.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE:: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN:: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS:: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS:: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-γ, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION:: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.
AIDS (London, England) 06/2013; 27(9):1421-1431. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score > F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (< 800 000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P = 0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P = 0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P = 0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.
[Show abstract][Hide abstract] ABSTRACT: AIMS: Studying alcohol abuse impact, as measured by physicians' perceptions and patients' self-reports, on HIV virological rebound among patients chronically co-infected with HIV and hepatitis C virus (HCV). DESIGN: Cohort study. SETTING: Seventeen French hospitals. PARTICIPANTS: 512 patients receiving antiretroviral therapy (ART) with an undetectable initial HIV viral load and at least two viral load measures during follow-up. MEASUREMENTS: Medical records and self-administered questionnaires. HIV virological rebound defined as HIV viral load above the limit of detection of the given hospital's laboratory test. Alcohol abuse defined as reporting to have drunk regularly at least 4 (for men) or 3 (for women) alcohol units per day during the previous six months. Correlates of time to HIV virological rebound identified using Cox proportional hazards models. FINDINGS: At enrolment, nine percent of patients reported alcohol abuse. Physicians considered 14.8% of all participants as alcohol abusers. Self-reported alcohol abuse was independently associated with HIV virological rebound (hazard ratio [95% confidence interval]: 2.04 [1.13-3.67]; p=0.02), after adjustment for CD4 count, time since ART initiation and hospital HIV caseload. No significant relationship was observed between physician-reported alcohol abuse and virological rebound (p=0.87). CONCLUSIONS: In France, the assessment of alcohol abuse in patients co-infected with HIV and hepatitis C virus should be based on patients' self-reports, rather than physicians' perceptions. Baseline screening of self-reported alcohol abuse may help identify co-infected patients at risk of subsequent HIV virological rebound.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The aim of this study was to describe changes in repeated liver stiffness (LS) measurements and to assess the determinants of increase in LS in HIV-HCV-coinfected patients. METHODS: HIV-HCV-coinfected adults enrolled in the ANRS CO 13 HEPAVIH cohort, for whom two results of LS, evaluated over ≥24 months, were available. Patients with unreliable LS results were not included. LS was measured at baseline and every year thereafter. Determinants of LS increase were assessed using linear (primary outcome: last LS minus first LS value) and logistic (secondary outcome: ≥30% increase in the initial LS value) regression analyses. RESULTS: A total of 313 patients (mean age 45 years, 67.4% male) were included. Overall, 93.9% were receiving antiretroviral treatment (ART). The mean baseline CD4(+) T-cell count was 471 cells/mm(3) and 72.2% of patients had undetectable plasma HIV RNA. The mean interval between the first and last LS measurements was 33.5 months. No significant difference was found between baseline and follow-up mean LS values (P=0.39). However, a decrease of ≥30% in LS was observed in 48 (15.3%) patients and an increase of ≥30% in 64 (20.5%) patients. In multivariate linear and logistic analyses, excessive alcohol intake (β coefficient 6.8; P=0.0006) and high HCV viral load (OR 1.7, 95% CI 1.1, 2.5; P=0.01) were independently associated with an increase in LS, whereas time on ART>114.5 months (OR 0.5, 95% CI 0.3, 0.9; P=0.03) and achievement of sustained virological response (OR 0.1, 95% CI 0.01, 0.9; P=0.04) were independently associated with no increase in LS. CONCLUSIONS: Our findings show that long-term ART and achieving sustained virological response in HIV-HCV-coinfected patients are both significantly associated with lack of increase in LS over a 33-month period.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE(S):: to examine the impact of ribavirin and abacavir coadministration on HCV virological response and trough ribavirin plasma concentration (Cmin) in HIV-HCV coinfected patients. DESIGN:: pharmacokinetic substudy on patients from the ANRS CO-13 HEPAVIH cohort. METHODS:: Patients receiving ribavirin plus Peg-IFN for whom a ribavirin steady state Cmin was prospectively determined were included. Rapid (RVR), early (EVR) and sustained (SVR) virological response as well as HCV-RNA decline were evaluated. RESULTS:: Overall, 124 HIV-HCV coinfected patients (95% on antiretroviral therapy) were enrolled. Of these patients, 22% received abacavir. The overall median (IQR) ribavirin Cmin was 1.6 mg/L (1.2-2.2) with no statistical difference between abacavir users and non-users [1.5 mg/L (0.99-2.1) and 1.7 (1.2-2.3), p = 0.15]. RVR and EVR were 52% and 72%, respectively. There was no difference observed in the proportion of abacavir users versus non-users achieving RVR (respectively 59% versus 50%, p = 0.40) or EVR (72% versus 73%, p = 0.94), or in the HCV-RNA decline at week 4 [-2.24 log10 IU/ml, (-3.58; -0.81) and -1.27 (-2.8; -0.47) p = 0.28] or at week 12 [-1.76 log10 IU/ml (-3.67; -0.35) and -1.85 (-3.13; -1.13) (p = 0.58)]. The SVR rate was 45% for abacavir users and 24% for abacavir non-users, but the difference was not statistically significant (p = 0.059). CONCLUSIONS:: In our study, there was no evidence that abacavir affected HCV treatment outcomes and the ribavirin Cmin was similar in abacavir users and non-users, confirming the absence of pharmacokinetic interaction between abacavir and ribavirin. An abacavir-containing regimen is therefore a safe treatment alternative for coinfected patients starting HCV treatment.
AIDS (London, England) 07/2012; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychiatric disorders are relatively common among HIV-infected patients. However, there are few studies about their potential risk factors. This analysis aimed to measure the incidence of severe psychiatric events (PE) among patients receiving combination antiretroviral therapy (cART) of the French APROCO-COPILOTE (ANRS CO8) cohort, and to identify the medical and socio-behavioural correlates of their first episode of depression, suicide or suicide attempt (D/S/SA).
APROCO-COPILOTE is a cohort of patients started on a protease inhibitor regimen between 1997 and 1999, with prospective medical standardized records and self-administered questionnaires collecting socio-demographic and socio-behavioural data. This analysis included all 11-year follow-up visits for 1,095 patients having completed baseline self-administered questionnaires. A proportional hazard Cox model was used to identify the correlates of a first D/S/SA event.
The overall prevalence of severe PE remained low: 50 patients experienced 67 events (incidence rate [95% CI] =1.04 [0.82, 1.32] per 100 person-years). Depression (n=16), suicides (n=5) and suicide attempts (n=14) were the most frequently diagnosed PE (0.54 [0.39, 0.76] per 100 person-years) among 25 patients. Multivariate results showed that unemployment, unstable housing, detectable viral load and smoking more than 20 cigarettes/day were independently associated with D/S/SA.
Although the incidence of severe PE remained relatively low among the patients of APROCO-COPILOTE cohort, this study's results underline a clinically important problem in HIV-infected patients receiving cART. Furthermore, our findings not only emphasize the importance of comprehensive care, especially for socially vulnerable patients, but may also help future studies designed to assess the effectiveness of interventions in reducing the risk of PE during cART.
[Show abstract][Hide abstract] ABSTRACT: In the ANRS CO13 HEPAVIH Cohort, HCV RNA measurement was performed with one of the two available real-time PCR assays [Roche Cobas AmpliPrep-Cobas TaqMan HCV (CAP-CTM) and the Abbott Real-Time HCV (ART)], according to the assay used in each center. To comply with the recommendations for using the same assay in multicenter clinical trials, all the 204 samples analyzed with ART were retested retrospectively by CAP-CTM. The aim of this study was to assess the usefulness of this strategy in real-life situations. A significant and positive correlation was observed between HCV RNA levels measured in the same samples with ART and CAP-CTM with all the genotypes tested. However, in 33 of the 204 (16%) clinical samples, the individual difference between HCV RNA levels measured by both assays was above ±0.5 log(10)IU/ml. Such viral load variations above 0.5 log(10) should be considered as significant. HCV RNA levels estimated by CAP-CTM for genotype 4 were significantly lower than those for genotypes 1, 2, and 3 (P<0.0001). This study shows that using the same assay in multicenter trials and cohorts is still relevant due to inter-assay differences observed in HCV plasma load measurements.
Journal of virological methods 01/2012; 181(1):131-3. · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The recommendations for detecting latent tuberculosis infection (LTBI) before antitumour necrosis factor (anti-TNF) therapy are based on the tuberculin skin test (TST), which lacks both specificity and sensitivity and can lead to unnecessary treatment with antibiotics. A study was undertaken to investigate the effect of replacing TST with interferon γ (IFNγ) release assays (IGRA) in screening for LTBI and deciding to begin prophylactic antituberculosis (TB) antibiotics before anti-TNF therapy in immune-mediated inflammatory diseases.
In 15 tertiary care hospitals, consecutive patients with rheumatoid arthritis, spondylarthropathies or Crohn's disease were screened for LTBI before anti-TNF therapy with TST, QuantiFERON TB Gold in tube (QTF-Gold IT) and T-SPOT.TB at the same time. The potential diagnosis of LTBI and the effect on the decision to begin antibiotic prophylaxis were assessed.
Among 429 patients, 392 had results for the three tests. The results for TST, T-SPOT.TB and QTF Gold IT were positive for 35.2%, 15.1% and 9.9% of patients, respectively (p<0.0001). Antibiotics were required for 177 patients (45.2%) if positive TST results were included in the LTBI definition, 107 patients (27.3%) if TST results were replaced with results from one of the IGRA tests and 84 patients (21.4%) if TST results were replaced with QTF-Gold IT results (p<0.0001). The decision on the use of antibiotic prophylaxis was changed for 113 patients (28.8%, 95% CI 24.4% to 33.6%) if TST results were replaced with QTF-Gold IT results.
Replacing TST with IGRA for determining LTBI allowed the proportion of patients with immune-mediated inflammatory diseases needing prophylactic anti-TB antibiotics before beginning anti-TNF agents to be reduced by half. TrialRegNo: NCT00811343.
Annals of the rheumatic diseases 01/2012; 71(11):1783-90. · 8.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose of the study: To describe long-term incidence trends and median age at diagnosis for the three AIDS-defining cancers (ADC) in HIV-1- infected (HIV1+) patients compared to general population. To study the risk of ADC in HIV1+patients with good immune status (CD4≥500/mm3 for at least 2 years). Methods: Incident ADC (Kaposi's sarcoma [KS], non-Hodgkin's lymphomas [NHL] and cervix uteri cancer [CUC]) were retrieved in HIV1+adults followed in the French hospital database on HIV (FHDH) cohort between 1992 and 2009. Cancer incidence rates (IR) in general population were calculated using data from the French cancer registries (Francim network). IR among the HIV1+and the general population were standardized using the 5 years age and sex groups structure of the HIV1+population (1997-2009) and standardized incidence ratios (SIR) were estimated in HIV1+ patients vs. general population in 4 calendar periods (1992-1996, 1997-2000, 2001-2004, and 2005-2009). Median age at diagnosis was estimated after adjusting for the difference in age structure between HIV1+and general population. Summary of results: 5,935 incident ADC were diagnosed among 100,536 HIV1+ patients followed between 1992 and 2009. All ADC IRs were significantly reduced between pre- and post-cART eras and continue to decline in the cART period (p<10-4). SIR are presented in the table.Median age at diagnosis was significantly younger among HIV1+ patients than the general population for KS (40.4 vs. 42.5; p<10-4), NHL (41.4 vs. 52.5; p<10-4) and CUC (39.3 vs. 42.5; p<10-4). For HIV1+ patients under treatment who maintained controlled viral load (<500 copies/µL) and CD4 ≥500/mm3 for at least 2 years, the risk for KS, NHL and CUC were respectively SIR=71.6 (28.7-147.5), 2.4 (0.9-4.8) and 1.6 (0.3-4.7) vs. general population. Conclusions: The incidence rates of KS, NHL and CUC continued to decline through 2009 but the risk remained elevated as compared to general population in the most recent cART period. Despite the great reduction when compared to general population, the risk is still very high for KS in HIV1+patients who maintained CD4 ≥500/mm3 for at least 2 years. The risk was not significant for CUC and NHL.
Journal of the International AIDS Society 01/2012; 15(6):18196. · 3.94 Impact Factor