SARS-CoV-2 and the nervous system: review on pathogenesis of nervous system SARS-CoV-2 damage

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Evidence for Polymicrobic Flora Translocating in Peripheral Blood of HIV-Infected Patients with Poor Immune Response to Antiretroviral Therapy

In advanced HIV infection, the homeostatic balance between gastrointestinal indigenous bacteria and gut immunity fails and microbes are able to overcome the intestinal barrier and gain the systemic circulation. Because microbial translocation is not fully controlled by antiviral therapy and is associated with inefficient CD4+ reconstitution, we investigated the profile of translocating bacteria in peripheral blood of 44 HIV-infected patients starting therapy with advanced CD4+ T-lymphopenia and displaying poor CD4+ recovery on virologically suppressive HAART. According to CD4+ reconstitution at 12-months HAART, patients were considered Partial Immunological Responders, PIRs (CD4+≥250/µl, n = 29) and Immunological non Responders, INRs (CD4+<200/µl, n = 15)). We show that PIRs and INRs present similarly elevated plasma levels of lipopolysaccharide (LPS) and its ligand sCD14 that were not lowered by virologically suppressive therapy. Bacterial 16S rRNA gene amplification and sequencing resulted in a highly polymicrobic peripheral blood microbiota both prior and after 12-month HAART. Several differences in bacterial composition were shown between patients' groups, mainly the lack of probiotic Lactobacillaceae both prior and after therapy in INRs. Failure to control microbial translocation on HAART is associated with a polymicrobic flora circulating in peripheral blood that is not substantially modified by therapy

Reduced Central Memory CD4+ T Cells and Increased T-Cell Activation Characterise Treatment-Naive Patients Newly Diagnosed at Late Stage of HIV Infection

Objectives. We investigated immune phenotypes of HIV+ patients who present late, considering late presenters (LPs, CD4+ < 350/μL and/or AIDS), advanced HIV disease (AHD, CD4+ < 200/μL and/or AIDS), and AIDS presenters (AIDS-defining condition at presentation, independently from CD4+). Methods. Patients newly diagnosed with HIV at our clinic between 2007–2011 were enrolled. Mann-Whitney/Chi-squared tests and logistic regression were used for statistics. Results. 275 patients were newly diagnosed with HIV between January/2007–March/2011. 130 (47%) were LPs, 79 (29%) showed AHD, and 49 (18%) were AIDS presenters. LP, AHD, and AIDS presenters were older and more frequently heterosexuals. Higher CD8+%, lower CD127+CD4+%, higher CD95+CD8+%, CD38+CD8+%, and CD45R0+CD38+CD8+% characterized LP/AHD/AIDS presentation. In multivariate analysis, older age, heterosexuality, higher CD8+%, and lower CD127+CD4+% were confirmed associated with LP/AHD. Lower CD4+ and higher CD38+CD8+% resulted independently associated with AIDS presentation. Conclusions. CD127 downregulation and immune activation characterize HIV+ patients presenting late and would be studied as additional markers of late presentation

Abacavir and cardiovascular risk in HIV-infected patients: does T-lymphocyte hyperactivation exert a pathogenic role?

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Cost analysis of dalbavancin versus standard of care for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in two Italian hospitals

The study was presented at the 21st Conference of the National Society of Infectious Diseases and Tropical Medicine ‘Congresso Nazionale Società Italiana Malattie Infettive e Tropicali’, 20–23 November 2022, Rome, Italy (Poster PP259).OBJECTIVES: Thanks to its long half-life, dalbavancin qualifies as an optimal drug for saving costs. We aimed to assess the cost and effectiveness of dalbavancin versus the standard of care (SoC). PATIENTS AND METHODS: Thanks to its long half-life, dalbavancin qualifies as an optimal drug for saving costs. We aimed to assess the cost and effectiveness of dalbavancin versus the standard of care (SoC). RESULTS: One hundred and twenty-six of 228 (55.3%) patients received SoC, while 102/228 (44.7%) received dalbavancin. Twenty-seven of the 102 (26.5%) patients received dalbavancin as first-line treatment, 46 (45.1%) as second-line, and 29 (28.4%) as third- or higher-line treatment. Most patients received dalbavancin as monotherapy (62/102; 60.8%). Compared with SoC, dalbavancin was associated with a significant reduction of LOS (5 ± 7.47 days for dalbavancin, 9.2 ± 5.59 days for SoC; P < 0.00001) and with lower mean direct medical costs (3470 ± 2768€ for dalbavancin; 3493 ± 1901€ for SoC; P = 0.9401). LOS was also reduced for first-line dalbavancin, in comparison with second-, third- or higher-line groups, and for dalbavancin monotherapy versus combination therapy. Mean direct medical costs were significantly lower in first-line dalbavancin compared with higher lines, but no cost difference was observed between monotherapy and combination therapy. CONCLUSIONS: Monotherapy with first-line dalbavancin was confirmed as a promising strategy for ABSSSIs in real-life settings, thanks to its property in reducing LOS and saving direct medical costs.https://www.ncbi.nlm.nih.gov/pmc/journals/4039School of Health Systems and Public Health (SHSPH

One-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjects

OBJECTIVE: The aim of the ADONE (ADherence to ONE pill) study was to verify the effect of a reduced number of pills on adherence and quality of life (QoL) in HIV-infected patients on highly active antiretroviral therapy (HAART). DESIGN: Prospective, multicenter, study. METHODS: Patients chronically treated with emtricitabine (FTC) + tenofovir (TDF) + efavirenz (EFV) or lamivudine (3TC) +TDF +EFV and with a HIV-RNA < 50 copies/mL were switched to the single-pill fixed-dose regimen (FDR) of FTC +TDF +EFV. Data were collected with SF-36 using visual analog scales. Results of the final (6 months) primary as-treated analysis are reported. RESULTS: 212 patients (77.4% males) of mean age 45.8 years were enrolled; 202 completed the study. One month post switch to FDR the adherence rate increased significantly to 96.1% from a baseline value of 93.8% (P < 0.01). The increase was steadily maintained throughout the study (96.2% at 6 months). QoL improved over time from 68.8% to 72.7% (P = 0.042) as well, and was significantly associated with the perception of health status, presence of adverse events (AEs) and number of reported AEs (P < 0.0001). QoL significantly influenced adherence (P < 0.0001). During FDR use the mean CD4 count increased from 556 to 605 cells/muL (P < 0.0001). At the end of follow-up 98% of patients maintained HIV-RNA level < 50 copies/mL and 100% <400 copies/mL. Four patients stopped therapy because they were lost to follow-up and 6 because of AEs (insomnia/nervousness 4, allergy 1, difficulties swallowing pills 1). CONCLUSION: By substituting a one-pill once-a-day HAART, we observed an improvement of both adherence and QoL while maintaining high virologic and immunologic efficacy. HAART simplicity is an added value that favors adherence and may improve long-term success

Projections of non-communicable disease and health care costs among HIV-positive persons in Italy and the U.S.A.: A modelling study.

BACKGROUND: Country-specific forecasts of the growing non-communicable disease (NCD) burden in ageing HIV-positive patients will be key to guide future HIV policies. We provided the first national forecasts for Italy and the Unites States of America (USA) and quantified direct cost of caring for these increasingly complex patients. METHODS AND SETTING: We adapted an individual-based model of ageing HIV-positive patients to Italy and the USA, which followed patients on HIV-treatment as they aged and developed NCDs (chronic kidney disease, diabetes, dyslipidaemia, hypertension, non-AIDS malignancies, myocardial infarctions and strokes). The models were parameterised using data on 7,469 HIV-positive patients from the Italian Cohort Naïve to Antiretrovirals Foundation Study and 3,748 commercially-insured patients in the USA and extrapolated to national level using national surveillance data. RESULTS: The model predicted that mean age of HIV-positive patients will increase from 46 to 59 in Italy and from 49 to 58 in the USA in 2015-2035. The proportion of patients in Italy and the USA diagnosed with ≥1 NCD is estimated to increase from 64% and 71% in 2015 to 89% and 89% by 2035, respectively, driven by moderate cardiovascular disease (CVD) (hypertension and dyslipidaemia), diabetes and malignancies in both countries. NCD treatment costs as a proportion of total direct HIV costs will increase from 11% to 23% in Italy and from 40% to 56% in the USA in 2015-2035. CONCLUSIONS: HIV patient profile in Italy and the USA is shifting to older patients diagnosed with multiple co-morbidity. This will increase NCD treatment costs and require multi-disciplinary patient management

The interaction between a sexually transferred steroid hormone and a female protein regulates oogenesis in the malaria mosquito anopheles gambiae

Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that the mating-dependent pathway of egg development in these mosquitoes is regulated by the interaction between the steroid hormone 20-hydroxy-ecdysone (20E) transferred by males during copulation and a female Mating-Induced Stimulator of Oogenesis (MISO) protein. RNAi silencing of MISO abolishes the increase in oogenesis caused by mating in blood-fed females, causes a delay in oocyte development, and impairs the function of male-transferred 20E. Co-immunoprecipitation experiments show that MISO and 20E interact in the female reproductive tract. Moreover MISO expression after mating is induced by 20E via the Ecdysone Receptor, demonstrating a close cooperation between the two factors. Male-transferred 20E therefore acts as a mating signal that females translate into an increased investment in egg development via a MISO-dependent pathway. The identification of this male–female reproductive interaction offers novel opportunities for the control of mosquito populations that transmit malaria