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

Lactoferrin inhibits neutrophil apoptosis via blockade of proximal apoptotic signaling events

Neutrophils are the most abundant leukocyte and have a short lifespan, dying by apoptosis approximately five days after leaving the bone marrow. Their apoptosis can be delayed at sites of inflammation to extend their functional lifespan, but inappropriate inhibition of apoptosis contributes to chronic inflammatory disease. Levels of the physiological iron chelator lactoferrin are raised at sites of inflammation and we have shown previously that iron-unsaturated lactoferrin inhibited human neutrophil apoptosis, but the mechanisms involved were not determined. Here we report that the anti-apoptotic effect of lactoferrin is dependent upon its iron saturation status as iron-saturated lactoferrin did not affect neutrophil apoptosis. We also show that the effect of lactoferrin is mediated at an early stage in apoptosis as it inhibited activation of sphingomyelinase, generation of ceramide, activation of caspase 8 and Bax and cleavage of Bid. Lactoferrin did not inhibit apoptosis induced by exogenous ceramide, supporting the proposal that it acts upstream of ceramide generation. We therefore conclude that raised lactoferrin levels are likely to contribute to chronic inflammation by delaying neutrophil apoptosis and that this is achieved by inhibiting proximal apoptotic signaling events