Evaluation of the Hepatitis C Testing Strategy for Human Immunodeficiency Virus-Positive Men Who Have Sex With Men at the Sexually Transmitted Infections Outpatient Clinic of Amsterdam, the Netherlands

INTRODUCTION: As the incidence of hepatitis C virus (HCV) infections remains high among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) an HCV testing strategy was introduced at the sexually transmitted infections (STI) clinic in Amsterdam in 2017. We aimed to evaluate this HCV testing strategy. METHODS: The HIV-positive MSM and transgender women (TGW) were eligible for HCV testing (anti-HCV and HCV ribonucleic acid) at the STI clinic if they did not visit their HIV clinician in the 3 months before the consultation and had not been tested for HCV at the STI clinic in the previous 6 months. All eligible individuals were administered the 6 questions on risk behavior of the HCV-MSM observational study of acute infection with hepatitis C (MOSAIC) risk score; a risk score of 2 or greater made a person eligible for testing. RESULTS: From February 2017 through June 2018, 1015 HIV-positive MSM and TGW were eligible for HCV testing in 1295 consultations. Eleven active HCV infections (HCV ribonucleic acid positive) were newly diagnosed (positivity rate, 0.9%; 95% confidence interval [CI], 0.4-1.5%). Sensitivity and specificity of the HCV-MOSAIC score for newly diagnosed active HCV infections were 80.0% (95% CI, 49.0-94.3%) and 53.7% (95% CI, 50.8-56.5%), respectively. If an HCV-MOSAIC score of 2 or greater were used to determine whom to test, 46.6% of individuals currently tested for HCV would be eligible for testing. CONCLUSIONS: Using the new HCV testing strategy, HCV testing was done in 1295 consultations with HIV-positive MSM and TGW in 17 months. We newly diagnosed 11 active HCV infections. The HCV-MOSAIC risk score could reduce the number of tests needed, but some active HCV infections will be missed

IGFBP7 Induces Differentiation and Loss of Survival of Human Acute Myeloid Leukemia Stem Cells without Affecting Normal Hematopoiesis

Leukemic stem cells (LSCs) are thought to be the major cause of the recurrence of acute myeloid leukemia (AML) due to their potential for self-renewal. To identify therapeutic strategies targeting LSCs, while sparing healthy hematopoietic stem cells (HSCs), we performed gene expression profiling of LSCs, HSCs, and leukemic progenitors all residing within the same AML bone marrow and identified insulin-like growth factor-binding protein 7 (IGFBP7) as differentially expressed. Low IGFBP7 is a feature of LSCs and is associated with reduced chemotherapy sensitivity. Enhancing IGFBP7 by overexpression or addition of recombinant human IGFBP7 (rhIGFBP7) resulted in differentiation, inhibition of cell survival, and increased chemotherapy sensitivity of primary AML cells. Adding rhIGFBP7 reduced leukemic stem and/or progenitor survival and reversed a stem-like gene signature, but it had no influence on normal hematopoietic stem cell survival. Our data suggest a potential clinical utility of the addition of rhIGFBP7 to current chemotherapy regimens to decrease AML relapse rates