Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France)

<p>Abstract</p> <p>Background</p> <p>Treatment for the hepatitis C virus (HCV) may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population.</p> <p>Methods</p> <p>We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600) at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively.</p> <p>Results</p> <p>Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7%) had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]). Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians.</p> <p>Conclusions</p> <p>Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.</p

Ceruloplasmin expression by human peripheral blood lymphocytes: a new link between immunity and iron metabolism

Ceruloplasmin (CP) is a multicopper oxidase involved in the acute phase reaction to stress. Although the physiological role of CP is uncertain, its role in iron (Fe) homeostasis and protection against free radical-initiated cell injury has been widely documented. Previous studies showed the existence of two molecular isoforms of CP: secreted CP (sCP) and a membrane glycosylphosphatidylinositol (GPI)-anchored form of CP (GPI-CP). sCP is produced mainly by the liver and is abundant in human serum whereas GPI-CP is expressed in mammalian astrocytes, rat leptomeningeal cells, and Sertolli cells. Herein, we show using RT-PCR that human peripheral blood lymphocytes (huPBL) constitutively express the transcripts for both CP molecular isoforms previously reported. Also, expression of CP in huPBL is demonstrated by immunofluorescence with confocal microscopy and flow cytometry analysis using cells isolated from healthy blood donors with normal Fe status. Importantly, the results obtained show that natural killer cells have a significantly higher CP expression compared to all other major lymphocyte subsets. In this context, the involvement of lymphocyte-derived CP on host defense processes via its anti/prooxidant properties is proposed, giving further support for a close functional interaction between the immune system and the Fe metabolism

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010

<p>Abstract</p> <p>Background</p> <p>In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.</p> <p>To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.</p> <p>Methods</p> <p>Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrolment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrolment and yearly thereafter.</p> <p>Results</p> <p>A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/μl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status.</p> <p>Conclusion</p> <p>The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.</p

Impact of HCV treatment and depressive symptoms on adherence to HAART among coinfected HIV-HCV patients: results from the ANRS-CO13-HEPAVIH cohort.: HCV treatment and adherence to ART

International audienceBACKGROUND: The additional burden of HCV infection in HIV-HCV coinfected individuals may have some consequences on adherence to highly active antiretroviral therapy (HAART). Few studies have explored the pattern of correlates of non-adherence to HAART while simultaneously considering the impact of HCV treatment and depressive symptoms on adherence to HAART. We used longitudinal data to assess factors associated with non-adherence to HAART. METHODS: The French national prospective cohort ANRS-CO-13-HEPAVIH is a multi-center cohort which recruited 1175 HIV-HCV coinfected patients in 17 hospital outpatient units delivering HIV and HCV care in France between October 2006 and June 2008. For this analysis, we selected participants on HAART with self-reported data for adherence to HAART (n = 727 patients, 1190 visits). Data were collected using self-administered questionnaires and medical records. A mixed logistic regression model based on an exchangeable correlation matrix was used to identify factors associated with non-adherence to HAART. RESULTS: Patients reported non-adherence to HAART in 808 (68%) of the 1190 visits. Four variables remained associated with non-adherence to HAART after multivariate analysis: hazardous alcohol consumption, cocaine use and depressive symptoms, regardless of whether treatment for depression was being received. Finally, patients being treated for HCV infection were less likely to be non-adherent to HAART. CONCLUSIONS: Besides the problem of polydrug use, two other dimensions deserve special attention when considering adherence to HAART in HIV-HCV coinfected patients. Access to HCV treatment should be encouraged as well adequate treatment for depression in this population to improve adherence and response to HAART

Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: Results from the ANRS CO13 HEPAVIH cohort study

International audienceMethodsLongitudinal 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.ResultsAfter 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).ConclusionsElevated 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

Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: Results from the ANRS CO13 HEPAVIH cohort study

International audienceMethodsLongitudinal 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.ResultsAfter 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).ConclusionsElevated 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

Validation and comparison of simple noninvasive indexes for predicting liver fibrosis in HIV-HCV-coinfected patients: ANRS CO3 Aquitaine cohort.: Non invasive fibrosis indexes in HIV-HCV coinfected patients

International audienceBACKGROUND: Although an increasing number of noninvasive fibrosis markers are available in HCV-monoinfected patients, data on the performance of these tests in HIV-HCV-coinfected patients are lacking. OBJECTIVE: To assess the diagnostic performance for predicting hepatic fibrosis stage of four simple and inexpensive noninvasive indexes (FIB-4, APRI, Forns, and platelet count) in HIV-HCV-coinfected patients. METHODS: Two hundred consecutive HIV-HCV-coinfected patients from the ANRS-CO3 Aquitaine cohort who underwent liver biopsy were studied. Fibrosis stage was assessed according to Metavir scoring system by a single pathologist unaware of the data of the patients. Diagnostic performances were assessed by measuring the areas under the receiver operating characteristic curves (AUROC) and the percentage of patients correctly identified (PCI). RESULTS: For predicting significant fibrosis (F > or = 2), APRI, Forns index, and FIB-4 had AUROCS of 0.77, 0.75, and 0.79, with 39%, 25%, and 70% of PCI, respectively. For predicting severe fibrosis (F > or = 3), FIB-4 had AUROC of 0.77 with 56% of PCI. For predicting cirrhosis (F4), FIB-4, APRI, and platelet count had AUROCs of 0.80, 0.79, and 0.78, with 59%, 60%, and 76% of PCI, respectively. Overall, diagnostic performances of the different indexes did not differ significantly for both significant fibrosis and cirrhosis. CONCLUSION: The use of these noninvasive indexes could save liver biopsies in up to 56-76% of cases for the prediction of severe fibrosis-cirrhosis. However, given the high percentage of misclassified cases for significant fibrosis, such indexes do not appear currently suitable for use in clinical practice in HIV-HCV-coinfected patients

Primary liver cancer is more aggressive in HIV-HCV coinfection than in HCV infection. A prospective study (ANRS CO13 Hepavih and CO12 Cirvir).

International audienceOBJECTIVE: Since HAART, primary liver cancer has emerged as an increasing cause of morbidity and mortality in patients with HIV infection. Our aim was to compare characteristics and outcome of primary liver cancer according to HIV status in HCV cirrhotic patients submitted to periodic ultrasonographic surveillance. METHODS: All patients with primary liver cancer and cirrhosis were selected from two prospective cohorts (ANRS CO12 Cirvir, viral cirrhosis, n=1081; ANRS CO13 Hepavih, HIV-HCV coinfection, n=1175). Cirrhosis was diagnosed by liver biopsy in monoHCV group and biopsy and/or non-invasive tests in HIV-HCV group. Ultrasonographic surveillance was performed every 6 months. Diagnosis of primary liver cancer was established according to EASL-AASLD guidelines. RESULTS: Primary liver cancer was diagnosed in 32 patients, 16 in each group, and corresponded to hepatocellular carcinoma in all except for two cholangiocarcinomas in HIV-HCV patients. Ultrasonographic follow-up was similar (median time since last ultrasonographic without focal lesion: 237 days in HIV-HCV group (n=12) versus 208 days in HCV group, NS). At primary liver cancer diagnosis HIV-HCV patients were markedly younger (48 vs. 60 yrs, P<0.001), primary liver cancer was more advanced in HIV-HCV patients (single nodule: 43% vs. 75%, P=0.07; mean diameter of main nodule: 24 vs. 16 mm, P=0.006; portal obstruction: 3 vs. 0). Curative treatment was performed in four HIV-HCV patients versus 11 HCV patients (P=0.017). During follow-up, 10 HIV-HCV patients died versus only one HCV patient (P=0.0005). CONCLUSIONS: This result suggests more aggressiveness for tumors in HIV infected patients and, if confirmed, could result in shortening the length between ultrasonographic examinations

HIV-1 Tropism and Liver Fibrosis in HIV–HCV Co-Infected Patients

International audienceBackground and aims: Hepatic stellate cells, the major producers of extracellular matrix in the liver, and hepatocytes bear CXCR4 and CCR5, the two main co-receptors for entry of the human immunodeficiency virus (HIV). In vitro studies suggest that HIV-envelope proteins can modulate the replication of hepatitis C virus (HCV) and fibrogenesis. We investigated the influence of HIV tropism on liver fibrosis and the concentration of HCV RNA in HIV-HCV co-infected patients.Methods: We used a phenotypic assay to assess HIV tropism in 172 HCV-HIV co-infected patients: one group (75 patients) had mild fibrosis (score ≤F2) and the other (97 patients) had severe fibrosis (score >F2). We also assessed the relationship between HIV tropism and HCV RNA concentration in all these patients. We also followed 34 of these patients for 3 years to determine the evolution of HIV tropism and liver fibrosis, estimated by liver stiffness.Results: Initially, most patients (91.8%) received a potent antiretroviral therapy. CXCR4-using viruses were found in 29% of patients. The only factor associated with a CXCR4-using virus infection in multivariate analysis was the nadir of CD4 cells: <200/mm(3) (OR: 3.94, 95%CI: 1.39-11.14). The median HCV RNA concentrations in patients infected with R5 viruses, those with dual-mixed viruses and those with X4 viruses, were all similar. The prevalence of CXCR4-using viruses in patients with mild fibrosis (≤F2) (31%) and those with severe fibrosis (F3-F4) (28%, p = 0.6) was similar. Longitudinal analyses showed that the presence of CXCR4-using viruses did not increase the likelihood of fibrosis progression, evaluated by measuring liver stiffness.Conclusions: The presence of CXCR4-using viruses in patients receiving a potent antiretroviral therapy does not influence HCV RNA concentration or liver fibrosis