Coinfection with HIV and hepatitis C virus in 229 children and young adults living in Europe

[Objective] To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment.[Design] Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts.[Methods] Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included. Anonymized individual patient data were collected using a standard protocol and modified HIV Cohorts Data Exchange Protocol.[Results] Of 229 patients included, 142 (62%) had vertically acquired infection. Median age at last follow-up was 16.2 years. Most children had HCV genotype 1 (101/184, 55%) or 3 (57/184, 31%). One-fifth (46/214) had a previous AIDS diagnosis (data missing on prior AIDS diagnoses for 15). At their last clinic visit, 70% (145/208) had no/mild immunosuppression (Centers for Disease Control and Prevention stage 1), and 131 of 179 on antiretroviral therapy had undetectable HIV RNA (assay thresholds varied from <20 to <150 copies/ml). Overall, 42% (86/204) had hepatomegaly in the previous year, and 55% (116/213) had alanine aminotransferase more than 40 IU/l at their last test. Of 97 patients with transient elastography, 12 had results more than 9 kPa; this was associated with duration of HCV infection (P = 0.033), but not with CD4+ cell count, antiretroviral therapy use or sex in univariable analysis. Of 17 patients with liver biopsies, six had bridging fibrosis and one had cirrhosis. Twenty-five (11%) had been treated successfully for HCV.[Conclusion] The high proportion of patients with progressive liver disease underscores the need for close monitoring and earlier and more effective HCV treatment.This work was supported by funding from the EU Seventh Framework Programme (FP7/2007–2013) under EuroCoord grant agreement [no. 260694] and additional funding from Janssen.Peer reviewe

2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0

Background: The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. Guideline highlights: The 2019 Guidelines were extended with a new section focusing on drug–drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. Conclusions: The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish

The Role of Precision Medicine in the Diagnosis and Treatment of Patients with Rare Cancers.

Rare cancers pose unique challenges for patients and their physicians arising from a lack of information regarding the best therapeutic options. Very often, a lack of clinical trial data leads physicians to choose treatments based on small case series or case reports. Precision medicine based on genomic analysis of tumors may allow for selection of better treatments with greater efficacy and less toxicity. Physicians are increasingly using genetics to identify patients at high risk for certain cancers to allow for early detection or prophylactic interventions. Genomics can be used to inform prognosis and more accurately establish a diagnosis. Genomic analysis may also expose therapeutic targets for which drugs are currently available and approved for use in other cancers. Notable successes in the treatment of previously refractory cancers have resulted. New more advanced sequencing technologies, tools for interpretation, and an increasing array of targeted drugs offer additional hope, but challenges remain