Real-life study of dual therapy based on dolutegravir and ritonavir-boosted darunavir in HIV-1-infected treatment-experienced patients

<div><p>Background</p><p>Dual therapy based on dolutegravir and ritonavir-boosted darunavir (DTG/DRV/r) is a combination of well-known drugs with a high genetic barrier to HIV resistance.</p><p>Method</p><p>A retrospective analysis of all HIV-1 infected treatment-experienced patients who switched to DTG/DRV/r from May 2014 till March 2017 in 4 Polish centres–results of a 48-week treatment.</p><p>Results</p><p>The study group consisted of 59 men and 17 women. Median baseline parameters were: age– 42.7 years, CD4 cells count– 560.5 cells/μl, CD4 cells nadir– 150 cells/μl, <i>number</i> of prior antiretroviral <i>regimens–</i> 3. The introduction of dual therapy was primarily due to virologic failure (30 patients), adverse events on previous regimens (17 patients) and therapy simplification (27 patients). At week 48 the treatment <i>was continued</i> in 70/76 of patients and the median CD4 cells count increased from 560.5 to 641.0 cells/μl. The therapy was discontinued in six patients (1 –virologic failure, 1 –decrease of estimated glomerular filtration rate (eGFR), 1 –myalgia, 3 –lost to follow-up). At week 48 six patients had detectable viremia, but only in one patient viremia was higher than 200 copies/ml. At week 48 the level of serum total cholesterol of the investigated subjects was statistically significantly higher than at the moment of dual therapy introduction (185.8 mg/dl vs. 174.8 mg/dl- p<0.05). However, in patients previously not treated with TDF, there were no changes in lipid parameters during therapy. <i>Proteinuria</i> was observed in 13.2% of patients before the switch to dual therapy and in 7.1% of patients at week 48.</p><p>Conclusions</p><p>The investigated dual therapy was effective and safe. The observed increase in lipid parameters only concerned the patients who had used a TDF-based regimen prior to analysed dual treatment.</p></div

Exposure to dolutegravir in pregnant women living with HIV in Central and Eastern Europe and neighboring countries — data from the ECEE Network Group

Objectives: The purpose of this study was to investigate dolutegravir (DTG) use among women and exposure to DTG during pregnancy in real world in Central and Eastern Europe and neighboring countries. Material and methods: Centres from 20 countries included in the Euroguidelines in Central and Eastern Europe (ECEE) Network and Finland were asked to complete an on-line questionnaire. Results: Seven centres from Czech Republic, Finland, Greece, Poland, Slovakia, and Turkey provided detailed information. DTG exposure was reported in 415 women, of which 26 were during pregnancy. Of those, 22 were on DTG at the time of conception and 4 had started DTG during pregnancy. Few women had conventional risk factors. The data on folic acid usage was unknown for eight women; 14 were using and four were not using folic acid. Four pregnancies were ongoing at the time of the study and of those with an outcome, 77.3% resulted with term, 13.6% preterm delivery, 4.5% spontaneous and 4.5% medical abortion. Conclusions: The DTG signal report indicates the importance of safety research for drug use in pregnancy and highlights the urgent need for systematic surveillance of pregnancy outcomes and neonatal surveillance. Countries with low- or moderate HIV prevalence should be included in studies reviewing pregnancy outcomes and in any surveillance system to ensure the accuracy of drug safety revision

Dual therapy based on raltegravir and boosted protease inhibitors : the experience of Polish centers

Introduction: The aim of the study was to present the experience of Polish centers regarding dual therapy based on the integrase inhibitor raltegravir (RAL) and ritonavir-boosted protease inhibitors (PI/r) for treating treatment-naïve and -experienced HIV-infected patients. Material and methods: The paper concerns a retrospective multicenter study. The medical databases of six main Polish HIV centers from January 2009 to December 2014 were analyzed for the use of combined antiretroviral treatment consisting of RAL + PI/r. This study included 126 HIV-infected patients receiving RAL + PI/r therapy, of whom 17 patients were treatment-naive and 109 patients were treatment-experienced. Results: In treatment-experienced patients, the most common reasons for the introduction of a RAL + PI/r regimen were virologic failure and impaired renal function (45 of 109 patients). In the treatment-naïve group kidney disease was the cause of the RAL + PI/r regimen in 3 of 17 participants. In treatment-experienced patients, 80% of individuals still were on RAL + PI/r treatment after 12 months, 65% after 24 months and 53% of subjects after 60 months. In both groups, the simplification of the antiretroviral regimen was the most common reason for discontinuation of RAL + PI/r based therapy. Conclusions: In antiretroviral-experienced patients the dual therapy based on RAL + PI/s is safe and effective. In antiretroviral-naïve patients the RAL + PI/r regimen is rarely used in Poland

Meeting the WHO 90% target : antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics

Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. Methods: Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients’ characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01–2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08–2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04–2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29–2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01–4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52–5.26), p = 0.001]. Conclusions: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions

Recent advances in electromagnetic interference shielding properties of carbon-fibre-reinforced polymer composites—a topical review

Abstract Using carbon-fibre-reinforced polymer (CFRP) composites for electromagnetic interference (EMI) shielding has become a rapidly emerging field. This state-of-the-art review summarises all the recent research advancements in the field of electromagnetic shielding properties of CFRP composites, with exclusive attention paid to experimental work. It focuses on (1) important mechanisms and physical phenomena in the shielding process for anisotropic carbon-fibre composites and (2) shielding performance of CFRP materials as reported in the literature, with important performance-affecting parameters. The key properties which directly influence the shielding performance are identified, the most critical being the carbon-fibre concentration along with length for discontinuous carbon-fibre-filled polymers and the lay-up for continuous carbon-fibre-reinforced composites. The effect of adding conductive inclusions such as metal or carbon nanotubes is also reviewed. It is emphasised that processing conditions are strongly linked with the shielding properties of a composite. This is a first review, which covers all the recent advancements in the field of shielding properties of carbon-fibre-reinforced composites, with detailed analysis of factors influencing these properties and clear distinction between continuous and discontinuous reinforcement. It is shown that CFRP composites make a good candidate as an EMI shielding enclosure material

Experimental characterisation and prediction of shielding effectiveness for multilayer carbon fibre reinforced composite materials with varying configurations

This paper reports the outcomes of an experimental investigation of the shielding effectiveness (SE) for carbon fibre reinforced polymer (CFRP) composites with varying configurations. It focuses on (1) important parameters affecting the SE of CFRP laminates and (2) applicability of the transmission line (TL) theory to predict their shielding properties. Comparison of the SE profiles showed that quasi-isotropic and cross-ply configurations perform equally well in attenuating the unpolarised radiation and only a modest increase of 10 dB is achieved by doubling the number of plies due to increased absorption. The applicability of the TL model for CFRP composites was found to be limited to thin laminates with quasi-isotropic lay-up, for which the accuracy prediction was within 5 dB in the 150 MHz-1 GHz frequency range. The experimental SE values were also compared to the full wave simulation in a commercial electromagnetic simulation software, demonstrating more accurate predictions than any analytical model.</p

Adenovirus 36 Infection in People Living with HIV—An Epidemiological Study of Seroprevalence and Associations with Cardiovascular Risk Factors

Background. With the life expectancy of people living with HIV (PLHIV) rapidly approaching that of the general population, cardiovascular health in this group is as relevant as ever. Adenovirus 36 (Adv36) is one of the few viruses suspected to be a causative factor in promoting obesity in humans, yet there is a lack of data on this infection in PLHIV. Methods. PLHIV on stable suppressive antiretroviral therapy were included in the study, with assessment of anthropometric measures, blood pressure, serum lipid levels, fasting serum glucose and insulin, non-classical serum cardiovascular risk markers related to inflammation (hsCRP, resistin, calprotectin), and anti-Adv36 antibodies during a routine check-up. Results. 91 participants were recruited, of which 26.4% were Adv36-seropositive (Adv36(+)). Compared to Adv36-seronegative (Adv36(−)) controls, Adv36(+) individuals had a lower waist circumference (Adv36(+) 89.6 ± 7.7 cm, Adv36(−) 95.5 ± 11.7 cm, p = 0.024) and a lower waist-to-hip ratio (Adv36(+) 0.88 ± 0.06, Adv36(−) 0.92 ± 0.09, p = 0.014), but this did not reach statistical significance in the multivariate analysis (p > 0.05). Adv36(+) participants were less likely to be on lipid-lowering treatment (Adv36(+) 12.5%, Adv36(−) 34.3%, p = 0.042), even after adjustment for relevant baseline characteristics (OR = 0.23, 95%CI = 0.04–0.91), but no differences in cholesterol or triglyceride levels were found. No other statistically significant associations were observed. Conclusions. We found no evidence to support the claim that past Adv36-infection is associated with an increased prevalence of cardiovascular risk factors or with elevated inflammatory markers in PLHIV. More research is needed to replicate these findings in other samples of PLHIV and to compare them with the HIV-negative population