The global burden of HIV-1 drug resistance in the past 20 years

Genotypic drug resistance testing has been an integral part of the clinical management of HIV patients for almost 20 years, not only assisting treatment choices but also informing drug development. Accurate estimations on the worldwide circulation of drug resistance are difficult to obtain, particularly in low/middle-income countries. In this work, we queried two of the largest public HIV sequence repositories in the world-Los Alamos and Stanford HIVdb-to derive global prevalence, time trends and geodemographic predictors of HIV drug resistance. Different genotypic interpretation systems were used to ascertain resistance to reverse transcriptase and protease inhibitors. Continental, subtype-specific (including circulating recombinant forms) stratification as well as analysis on drug-naïve isolates were performed. Geographic information system analysis correlated country-specific drug resistance to sociodemographic and health indicators obtained from the World Bank. By looking at over 33,000 sequences worldwide between 1996 and 2016, increasing drug resistance trends with non-B subtypes and recombinants were found; transmitted drug resistance appeared to remain stable in the last decade. While an increase in drug resistance is expected with antiretroviral therapy rollout in resource-constrained areas, the plateau effect in areas covered by the most modern drug regimens warns against the downgrading of the resistance issue

Urban Heat Island (UHI) risk maps as innovative tool for urban regeneration strategies. The case of Parma

For the purposes of regeneration of the consolidated city it is increasingly important to have the knowledge of the micro-scale distribution of the vulnerability of the population to the consequences of climate change and increasing urbanization. The work to be presented starts with the creation of maps of the risk classification induced by the heat islands in the city of Parma, and aims to investigate which are the most effective strategies that a Public Administration can adopt. The maps that have been created allow to assess the risk for the fragile population at the level of the single building. They relate the climatic datum of thermal variation with the population residing within each building, and verify the causal relationship with the soil sealing and with the morphology of the urban fabric. The results of the study can help to identify the thermal hot spot, receivers of specific mitigation actions. The risk map is itself a tool to develop multilevel actions, designed according to the peculiarities of the sites, where the possible adaptive solutions are compared with the physical and morphological characteristics of the places. The positive function of green infrastructures (contrast of overheating, flood mitigation, creation of places and services with a recreational function) is acquired by research and urban planning practice. It is equally well known the difficulty faced by Local Authorities in the maintenance and increase of unbuilt public areas, fundamental for the connection of ecological networks

Towards the Definition of a Comprehensive Walkability Index for Historical Centres

Historical centres are crucial areas where urban and transport planners should aim at enhancing adequate walkability conditions. This should be considered a priority in order to allow all users, including the most vulnerable ones, to access the activities they wish to engage in. Based on this premises, the paper aims at defining a methodological approach to comprehensively assess the existing pedestrian network infrastructure within historical centres, considering safety, comfort and enjoyment factors of the walking experience. In-field inspections have been carried out for the main pedestrian paths and crossings within the historical centre of Parma and data have been georeferenced in a GIS database. The indicators considered in the walkability analysis are: sidewalks width, change of levels, bottlenecks, coloured ground signs, protection level, presence of seats, maintenance level and presence of tactile flooring. A comprehensive walkability index has been developed to assess the quality of each pedestrian link and crossing. The results have been represented in GIS-based thematic maps, that can support local authorities in defining priorities of intervention

Potential role of doravirine for the treatment of HIV-1-infected persons with transmitted drug resistance

Background: Doravirine has a unique resistance profile but how this profile might increase its usefulness beyond first-line therapy in persons with susceptible viruses has not been well studied. We sought to determine scenarios in which doravirine would retain activity against isolates from ART-naïve persons with transmitted drug resistance (TDR) and to identify gaps in available doravirine susceptibility data. Methods: We analyzed published in vitro doravirine susceptibility data and applied the results to 42,535 RT sequences from ART-naïve persons published between 2017 and 2021. NNRTI drug resistance mutations (DRMs) were defined as those with a Stanford HIV Drug Resistance Database doravirine penalty score either alone or in combination with other mutations. Results: V106A, Y188L, F227C/L, M230L, and Y318F were associated with the greatest reductions in doravirine susceptibility. However, several NNRTI DRMs and DRM combinations lacking these canonical resistance mutations had > tenfold reduced susceptibility including G190E, one isolate with G190S, three isolates with L100I + K103N, one isolate with K103N + P225H, and isolates with L100I + K103N + V108I and K101E + Y181C + G190A. Of the 42,535 ART-naïve sequences, 3,374 (7.9%) contained a NNRTI DRM of which 2,788 (82.6%) contained 1 DRM (n = 33 distinct mutations), 426 (12.6%) contained 2 DRMs (79 distinct pairs of mutations), and 143 (4.2%) contained ≥ 3 DRMs (86 distinct mutation patterns). Among the 2,788 sequences with one DRM, 112 (4.0%) were associated with ≥ 3.0-fold reduced doravirine susceptibility while 2,625 (94.2%) were associated with < 3.0-fold reduced susceptibility. Data were not available for individual NNRTI DRMs in 51 sequences (1.8%). Among the 426 sequences with two NNRTI DRMs, 180 (42.3%) were associated with ≥ 3.0 fold reduced doravirine susceptibility while just 32 (7.5%) had < 3.0 fold reduced susceptibility. Data were not available for 214 (50.2%) sequences containing two NNRTI DRMs. Conclusions: First-line therapy containing doravirine plus two NRTIs is expected to be effective in treating most persons with TDR as more than 80% of TDR sequences had a single NNRTI DRM and as more than 90% with a single DRM were expected to be susceptible to doravirine. However, caution is required for the use of doravirine in persons with more than one NNRTI DRM even if none of the DRMs are canonical doravirine-resistance mutations. © 2023, The Author(s)

Ohjelmistotyön tehostaminen automaatioympäristössä. Case: Jenkins

Tämän opinnäytetyön tarkoituksena oli toteuttaa Codecontrol Oy:lle avoimeen lähdekoodiin perustuvan web-pohjaisen Jenkins-palvelinsovelluksen asentaminen toimintakuntoon fyysiselle palvelimelle ja jakaa se usealle virtuaalipalvelimelle nykyisen yhden sijasta saaden kokonaisuus hyödyntämään master-slave -arkkitehtuurin mukaista ohjelmistoautomatisointimallia. Ennen varsinaista toteutusosuutta tämän opinnäytetyön teoriaosuudessa kerrotaan jatkuvasta integraatiosta ja jatkuvasta kehityksestä sekä niiden merkityksestä ohjelmistokehitykselle. Teoriaosuuden lopuksi esitellään toteutuksessa asennettava web-pohjainen palvelinsovellus Jenkins.The purpose of this thesis was to implement an open source web-based Jenkins server application installation into physical server for Codecontrol Oy and distribute it to multiple virtual servers instead of the existing one, thus enabling the whole utilization of the master-slave -architecture-based software automation model. Before the actual implementation part, the theoretical part of this thesis tells about continuous integration and continuous development and their significance for software development. Web-based server application Jenkins is introduced at the end of the theoretical part

Criteri e metodi per la rigenerazione urbana diffusa del tessuto residenziale consolidato

All’interno del dibattito urbanistico sui temi della rigenerazione urbana, il contributo proposto intende condividere i primi esiti di una ricerca in corso presso l’ateneo di Parma e di portare una riflessione circa la necessità, e le possibili modalità di attuazione, di una pianificazione degli interventi di rigenerazione urbana diffusa del tessuto consolidato, ed interrogarsi sugli strumenti con cui affrontare tali processi di rigenerazione, sia in termini di costruzione del quadro conoscitivo che di indirizzi di azione. Il fine è quello di definire una proposta di metodo per una prima analisi del tessuto urbano consolidato alla scala comunale, attraverso cui definire e pianificare gli ambiti prioritari su cui attuare interventi di riuso e rigenerazione di parti del territorio urbanizzato a prevalente destinazione residenziale, includendo l’individuazione di set di dati e di possibili indicatori per l’individuazione degli ambiti prioritari da assoggettare a rigenerazione urbana. Tra gli altri, sono considerati criteri quali la destinazione d’uso, la datazione e lo stato di conservazione degli edifici, ma anche la densità, la dotazione di standard e di servizi e i livelli di accessibilità del tessuto residenziale. La metodologia è in corso di applicazione al caso studio del comune di Parma, per il quale sono stati archiviati dati GIS relativi alla città consolidata per una superficie di oltre 2400 ha, effettuate elaborazioni statistiche, e compilate schede di rilievo che individuano le potenzialità e le criticità presenti sul tessuto residenziale e i possibili scenari, anche contrapposti, d’intervento

Changing patterns in HIV-1 non-B clade prevalence and diversity in Italy over three decades

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Bithiazole Inhibitors of Phosphatidylinositol 4-Kinase (PI4KIIIβ) as Broad-Spectrum Antivirals Blocking the Replication of SARS-CoV-2, Zika Virus, and Human Rhinoviruses

Over half a century since the description of the first antiviral drug, “old” re-emerging viruses and “new” emerging viruses still represent a serious threat to global health. Their high mutation rate and rapid selection of resistance toward common antiviral drugs, together with the increasing number of co-infections, make the war against viruses quite challenging. Herein we report a host-targeted approach, based on the inhibition of the lipid kinase PI4KIIIβ, as a promising strategy for inhibiting the replication of multiple viruses hijacking this protein. We show that bithiazole inhibitors of PI4KIIIβ block the replication of human rhinoviruses (hRV), Zika virus (ZIKV) and SARS-CoV-2 at low micromolar and sub-micromolar concentrations. However, while the anti-hRV/ZIKV activity can be directly linked to PI4KIIIβ inhibition, the role of PI4KIIIβ in SARS-CoV-2 entry/replication is debated

Local epidemics gone viral: Evolution and diffusion of the Italian HIV-1 recombinant form CRF60_BC

The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18-37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy