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

Delay in diagnosis and treatment of patients with cases of imported malaria in Poland : one center’s experience

Background . Increasingly, Polish citizens are traveling to malaria endemic regions; thus, physicians, especially primary care physicians, should be educated to recognize and treat malaria. Diagnosis and treatment of malaria encounters many difficulties in Poland. Objectives . The aim of the study was to analyze malaria chemoprophylaxis, the time from first symptoms to hospitalization and the process of diagnosis and treatment of patients with malaria. Material and methods . The medical records of patients diagnosed with malaria, hospitalized between 2012 and 2016 in the Department of Infectious Diseases of the University Hospital, Cracow, Poland, were analyzed. Results . 37 subjects with a median age of 32 years (interquartile range IQR: 28–40), mostly returning from Africa (78%, n = 29), were studied. Proper chemoprophylaxis was used in 6 cases (16%). The median length of stay in malaria endemic countries was one month. Plasmodium falciparum was the most frequent species (74%). The mean time to treatment after symptom onset was 5 days (range: 1–27 days). Conclusions . The clinical presentation of malaria in the study group was usually typical. Diagnostic delay resulted from not taking malaria into consideration during the initial differential diagnosis of fever. Few travelers use chemoprophylaxis, hence the awareness of malaria in individuals who have traveled to endemic zones should be enhanced. In a patient presenting with fever, malaria should always be considered in a differential diagnosis if there is a history of travel to a malaria-endemic zone

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

Design and synthesis of new quinazolin-4-one derivatives with negative mGlu7mGlu_7 receptor modulation activity and antipsychotic-like properties

Following the glutamatergic theory of schizophrenia and based on our previous study regarding the antipsychotic-like activity of mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM mGlu7 activity in the T-REx 293 cell line expressing a recombinant human mGlu7 receptor. Out of the twenty-two scaffolds examined, active compounds were found only within the quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, mGlu7 IC50 = 6.14 &micro;M) was selective over other group III mGlu receptors (mGlu4 and mGlu8), exhibited satisfactory drug-like properties in preliminary DMPK profiling, and was further tested in animal models of antipsychotic-like activity, assessing the positive, negative, and cognitive symptoms. ALX-171 reversed DOI-induced head twitches and MK-801-induced disruptions of social interactions or cognition in the novel object recognition test and spatial delayed alternation test. On the other hand, the efficacy of the compound was not observed in the MK-801-induced hyperactivity test or prepulse inhibition. In summary, the observed antipsychotic activity profile of ALX-171 justifies the further development of the group of quinazolin-4-one derivatives in the search for a new drug candidate for schizophrenia treatment