The use and impact of European Testing Week regional awareness campaigns to increase HIV and viral hepatitis testing coverage

Introduction Since 2013, the European Testing Week (ETW) awareness campaign has become a key regional event influencing testing efforts for HIV, viral hepatitis, and sexually transmitted infections (STIs) through participation of 720 organizations. Here, we report on a survey from May to June 2022 aimed at assessing the participant-reported impact of the campaign. Methods All past and current participating organizations were asked to complete an online questionnaire between 12 May and 17 June 2022. Multiple choice and open-text questions included organization information, usage of ETW to engage in local testing-related activities, and the effect of a regional campaign to reach a wider audience and generate impact. Results Of the 52 respondents, 34 (65%) stated first participating in ETW 5–10 years ago. ETW was used for awareness raising by 40 respondents (83%), new testing activities by 37 (77%), advocacy initiatives by 15 (31%), and training/capacity building by 18 (38%). For awareness raising, 95% used ETW to highlight the importance of and to encourage testing; for new testing activities, 74% used ETW to reach new groups. In total, 44 (85%) reported added benefits of a Europe-wide campaign compared with national/local campaigns, particularly the increased visibility and collaboration opportunities. Impact at the local level was observed by 24 (51%), and impact at a national level was observed by 20 (43%). A total of 28 (79%) reported increases in the number of tests performed and 25 (75%) reported increases in clients accessing services. Conclusions Regional awareness campaigns reach wider audiences, boost local and national efforts to increase testing, and sensitize key populations about the critical value of testing compared with local/national campaigns.info:eu-repo/semantics/publishedVersio

Transmission of Human Immunodeficiency Virus I Drug Resistance - a Case Report. What are the Clinical Implications?

The success of first-line antiretroviral therapy can be challenged by the acquisition of primary drug resistance. Here we report a case where baseline genotypic resistance testing detected resistance conferring nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-associated mutations, but no primary mutations for protease inhibitor (PI). Subsequent PI-based HAART with boosted saquinavir led to virological treatment success with persistently undetectable viral load. After treatment simplification from saquinavir to an atazanavir based PI-therapy and no change in backbone therapy rapid virological breakthrough occurred. Retrospective analysis displayed preexisting gag cleavage site mutations which may have reduced the genetic barrier in a clinical relevant manner in combination with the already existing NRTI resistance mutations. Alternatively, this effect could be explained with a different antiviral potency for the respective PIs used

Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.

In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24 <sup>Gag</sup> vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI. All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log <sub>10</sub> -transformed VL (VE <sup>VL</sup> ) or CD4 count (VE <sup>CD4</sup> ). A lower fold-change of CD4+ T-cell proliferation was associated with VE <sup>CD4</sup> at week 48 (p=0.036, multiplicity adjusted q=0.036) and week 52 (p=0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VE <sup>VL</sup> at week 44 (p=0.047, q=0.07). A higher fold-change of TNF-α was associated with VE <sup>VL</sup> at week 44 (p=0.045, q=0.070), week 48 (p=0.028, q=0.070), and week 52 (p=0.037, q=0.074). A higher fold-change of IL-6 was associated with VE <sup>VL</sup> at week 48 (p=0.017, q=0.036). TNF-α levels (>median) were associated with VE <sup>CD4</sup> at week 48 (p=0.009, q=0.009). These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies

Cancer risk in HIV-infected individuals on HAART is largely attributed to oncogenic infections and state of immunocompetence

<p>Abstract</p> <p>Objectives</p> <p>To estimate the cancer risk of HIV-infected patients in the HAART era with respect to a general reference population and to determine risk factors for malignancy.</p> <p>Methods</p> <p>Long term (1996-2009) cancer incidence of the Bonn single centre HIV cohort was compared to the incidence of the reference population of Saarland using standardized incidence ratios (SIR). Poisson regression analysis was used to identify predictors of cancer risk.</p> <p>Results</p> <p>1,476 patients entered the cohort, enabling 8,772 person years of observation. 121 tumours in 114 patients, 7 in-situ and 114 invasive cancers, were identified. Malignancies associated with infectious agents such as Kaposi sarcoma (SIRs: male: 5,683; female: 277), non-Hodgkin lymphoma (SIRs male: 35; female: 18), anal cancer (SIRs male: 88; female: 115) as well a cervical carcinoma (SIR female: 4) and Hodgkin's disease (SIR male: 39) and liver cancer (SIR male: 18) were substantially more frequent in HIV-infected patients than in the general population (p < 0.001, each), whereas all other types of cancer were not increased. Poisson regression identified HAART (incidence rate ratio IRR (95% CI): 0.28 (0.19-0.41), p < 0.001), CD4 count (IRR per 100 cells/μl increase: 0.66 (0.57-0.76), p < 0.001), hepatitis B (IRR: 2.15 (1.10-4.20), p = 0.046) and age (IRR per 10 year increase: 1.23 (1.03 - 1.46), p = 0.023) as independent predictors for the occurrence of any type of cancer.</p> <p>Conclusions</p> <p>HAART and preserved CD4 cells preferentially reduce the risk of malignancies associated with oncogenic infections.</p

Modified bibenzimidazole ligands as spectator ligands in photoactive molecular functional Ru-polypyridine units? Implications from spectroscopy

The photophysical properties of Ruthenium-bipyridine complexes bearing a bibenzimidazole ligand were investigated. The nitrogens on the bibenzimidazole-ligand were protected, by adding either a phenylene group or a 1,2-ethandiyl group, to remove the photophysical dependence of the complex on the protonation state of the bibenzimidazole ligand. This protection results in the bibenzimidazole ligand contributing to the MLCT transition, which is experimentally evidenced by (resonance) Raman scattering in concert with DFT calculations for a detailed mode assignment in the (resonance) Raman spectra

Ligand electronic fine-tuning and its repercussion on the photocatalytic activity and mechanistic pathways of the copper-photocatalysed aza-Henry reaction

A family of six structurally related heteroleptic copper(i) complexes of the form of [Cu(N^N)(P^P)]+ bearing a 2,9-dimethyl-1,10-phenanthroline diimine (N^N) ligand and a series of electronically tunable xantphos (P^P) ligands have been synthesized and their optoelectronic properties characterized. The reactivity of these complexes in the copper-photocatalyzed aza-Henry reaction of N-phenyltetrahydroisoquinoline was evaluated, while the related excited state kinetics were comprehensively studied. By subtlety changing the electron-donating properties of the P^P ligands with negligible structural differences, we could tailor the photoredox properties and relate them to the reactivity. Moreover, depending on the exited-state redox potential of the catalysts, the preferred mechanism can shift between reductive quenching, energy transfer and oxidative quenching pathways. A combined study of the structural modulation of copper(i) photocatalysts, optoelectronic properties and photocatalytic reactivity resulted in a clearer understanding of both the rational design of the photocatalyst and the complexity of competing photoinduced electron and energy transfer mechanisms. © The Royal Society of Chemistry

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment