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Background The London patient (participant 36 in the IciStem cohort) underwent allogeneic stem-cell transplantation with cells that did not express CCR5 (CCR5 Delta 32/Delta 32); remission was reported at 18 months after analytical treatment interruption (ATI). Here, we present longer term data for this patient (up to 30 months after ATI), including sampling from diverse HIV-1 reservoir sites. Methods We used ultrasensitive viral load assays of plasma, semen, and cerebrospinal fluid (CSF) samples to detect HIV-1 RNA. In gut biopsy samples and lymph-node tissue, cell-copy number and total HIV-1 DNA levels were quantified in multiple replicates, using droplet digital PCR (ddPCR) and quantitative real-time PCR. We also analysed the presence of intact proviral DNA using multiplex ddPCR targeting the packaging signal (psi) and envelope (env). We did intracellular cytokine staining to measure HIV-1-specific T-cell responses. We used low-sensitive and low-avidity antibody assays to measure the humoral response to HIV-1. We predicted the probability of rebound using a mathematical model and inference approach. Findings HIV-1 viral load in plasma remained undetectable in the London patient up to 30 months (last tested on March 4, 2020), using an assay with a detection limit of 1 copy per mL. The patient's CD4 count was 430 cells per mu L (23.5% of total T cells) at 28 months. A very low-level positive signal for HIV-1 DNA was recorded in peripheral CD4 memory cells at 28 months. The viral load in semen was undetectable in both plasma (lower limit of detection [LLD]

PURPOSE: To determine the efficacy and safety data of aflibercept+FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy+anti-EGFR treatment. METHODS: Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy+anti-EGFR treatment. RESULTS: A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9months (95%CI: 6.1-7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5months (95%CI: 9.7-19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%). TOXICITY: Grade 3-4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients. CONCLUSIONS: The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.

HIV-1 infection remains incurable despite the efficient combined antiretroviral therapy (cART) due to the formation of long-lived viral reservoirs that are mostly settled in CD4+T cells and maintained by homeostatic proliferation. The use of cytostatic drugs such as tyrosine kinase inhibitors (TKIs) as adjuvants to cART could be helpful to avoid the reservoir establishment and replenishment. We determined previously that TKI dasatinib, which is successfully used for treating chronic myeloid leukemia (CML), shows antiviral effect against HIV-1 infection of CD4 + T cells in vitro. HIV-infected subjects that developed CML may safely combine long-term treatment with TKIs and cART but there is no information about the effect of dasatinib on HIV-1 reservoir in vivo. Therefore, we analyzed the ability of dasatinib to protect NSG mice engrafted with human CD34 + hematopoietic stem cells from HIV-1 infection. Mice were randomly assigned to two groups that received dasatinib or placebo daily by oral gavage. After five days, all mice were infected intraperitoneally with HIV-1 and followed up for 21?days in the absence of cART. Daily administration of dasatinib decreased viral and proviral load in all treated mice, showing in 40% of these mice undetectable viral RNA or DNA in blood. Proviral HIV-1 DNA in gut-associated lymphoid tissue (GALT) was also reduced in all dasatinib-treated mice and under the limit of detection in one of these mice. Finally, treatment with dasatinib modified the distribution of CD4 + and CD8 + T-cell subpopulations, delaying their differentiation into memory T-cell subsets that are a major component of the viral reservoir. In conclusion, dasatinib afforded protection of NSG mice from HIV-1 intraperitoneal infection in the absence of cART.

La enfermedad cardiovascular (ECV) es la principal causa de muerte en Argentina. Los modelos de simulació;n por computadora permiten extrapolar evidencia a poblaciones más amplias que las originalmente estudiadas, a lo largo de períodos prolongados, y comparar diferentes subpoblaciones. El Cardiovascular Disease Policy Model (CVDPM, por sus siglas en ingló;©s) es un modelo de simulació;n utilizado para representar y proyectar la mortalidad y morbilidad por ECV en la població;n de 35 o más aó;±os. El objetivo de este trabajo fue actualizar la versió;n argentina del CVDPM. Para esto, se utilizó; informació;n del Censo Nacional 2010, la Encuesta Nacional de Factores de Riesgo 2013, el estudio CESCAS I, y el estudio PrEViSTA, para actualizar la dinámica del tamaó;±o de la població;n, sus características demográficas, y la distribució;n de factores de riesgo cardiovasculares a lo largo del tiempo. Las proyecciones del modelo se calibraron comparándolas con informació;n sobre eventos de ECV y mortalidad en el aó;±o 2010 (aó;±o de referencia) en Argentina. Las estadísticas argentinas informaron que en 2010 la població;n de 35 o más aó;±os sufrió; un total de 41 219 infartos de miocardio (IM), 58 658 accidentes cerebrovasculares y 281 710 muertes totales. El CVDPM predijo 41 265 IM (diferencia: 0.11%), 58 584 accidentes cerebrovasculares (diferencia: 0.13%) y 280 707 muertes totales (diferencia: 0.36%). En todos los casos, la versió;n final del modelo predijo el nó;ºmero real de eventos cardiovasculares con una precisió;n superior al 99.5%, pudiendo ser utilizado para pronosticar cambios en la incidencia y mortalidad de ECV debidos de la implementació;n de políticas pó;ºblicas. Cardiovascular disease (CVD) is the leading cause of death in Argentina. Computer simulation models allow to extrapolate evidence to broader populations than the originally studied, over longer timeframes, and to compare different subpopulations. The Cardiovascular Disease Policy Model (CVDPM) is a computer simulation state transition model used to represent and project future CVD mortality and morbidity in the population 35 years-old and older. The objective of this study was to update Argentina’s version of the CVDPM. For this purpose, information from the 2010 National Census, the 2013 National Risk Factor Survey, CESCAS I study, and PrEViSTA study were used to update the dynamics of population size, demographics, and CVD risk factor distributions over time. Model projections were later calibrated by comparing them to actual data on CVD events and mortality in the year 2010 (baseline year) in Argentina. Country statistics for people 35 years-old and older reported for 2010 a total of 41 219 myocardial infarctions (MIs), 58 658 strokes, and 281 710 total deaths. The CVDPM, in turn, predicted 41 265 MIs (difference: 0.11%), 58 584 strokes (difference: 0.13%), and 280 707 total deaths (difference: 0.36%) in the same population. In all cases, the final version of the model predicted the actual number of events with an accuracy superior to 99.5%, and could be used to forecast the changes in CVD incidence and mortality after the implementation of public policies.