The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

A Decision Support Visualization Tool for Infection Management Based on BMPN and DMN

The interdisciplinary team of an Antimicrobial Stewardship Program is indispensable to preserve the antibiotic utility and avoid resistance in a hospital. One key duty of this team is the administration behaviour surveillance, which is a complex and tedious issue. In this work we present a tool to support this supervision by visualising some essential elements of the antimicrobial therapy: patient record, guidelines and key decision actions. The tool uses standardized models of industry (BPMN, DMN) to ease its maintenance in the long term and its interopreability

Formation and Survival of Oospores of Phytophthora-Infestans Under Natural Conditions

Phytophthora infestans is able to produce oospores in leaves of potato and tomato plants after inoculation with a mixture of A1 and A2 mating-type isolates. Various conditions for oospore formation were analysed. Under controlled conditions, oospores were produced in potato leaves at temperatures ranging from 5 to 25 degrees C. In leaves of potato cultivar Bintje incubated at 15 degrees C, oogonia and antheridia were observed 6 days after inoculation and thick-walled oospores appeared 3-4 days later. In field experiments oospores were found in leaves and stems of potato cultivars Bintje, Irene and Pimpernel and in leaves, stems and fruits of tomato cultivar Moneymaker within 2 weeks after inoculation. A bioassay was developed to test the survival of oospores in soil under various conditions. To determine whether late-blight infections derived from infectious soil were caused by oospores, DNA fingerprinting was performed. DNA fingerprint probe RG-57 was suitable for distinguishing asexual progeny from recombinant progeny arising from soil-borne oospores. We demonstrated survival of viable, infectious oospores of P. infestans in soil during the winter of 1992-93. Oospores were not infectious from soil exposed to temperatures of 40 degrees C or higher but in the range 35 degrees C to as low as -80 degrees C for 48 h, oospores survived

Molecular evidence for natural interspecific hybridization in Prosopis

Interspecific hybridization can occur under natural conditions among species of the Prosopis genus, potentially giving rise to hybrid individuals with increased adaptation values. A study was conducted to assess the occurrence of interspecific hybridization among Prosopis in the Argentinian Chaco region and the species involved. The survey included seven hybrid individuals and their potential parents. Principal component analysis (PCA) was carried out based on 16 morphological characters. The molecular marker study was carried out by the comparison of RAPD patterns of amplification using six primers. A total of 91 RAPD fragments were analysed, yielding 33 species-specific markers, 24 bands that were common to two or three parental lines, and 22 bands of unknown origin. The dendrograms arising from Nei’s genetic distances derived from the molecular data showed a clustering pattern in agreement with the grouping obtained by the PCA of the morphological traits. The results demonstrate the occurrence of interspecific hybridization involving Prosopis alba, P. nigra and P. hassleri in the Argentinian Chaco.Financial support from SECyT, Argentina (project number 09-002/02) and from MCYT, Spain(project number AGL2003-00720) is gratefullyacknowledgedPeer reviewe