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

Molecular origin of the two-step mechanism of gellan aggregation

Among hydrocolloids, gellan is one of the most studied polysaccharides due to its ability to form mechanically stable gels. Despite its long-standing use, the gellan aggregation mechanism is still not understood because of the lack of atomistic information. Here, we fill this gap by developing a new gellan force field. Our simulations offer the first microscopic overview of gellan aggregation, detecting the coil to single-helix transition at dilute conditions and the formation of higher-order aggregates at high concentration through a two-step process: first, the formation of double helices and then their assembly into superstructures. For both steps, we also assess the role of monovalent and divalent cations, complementing simulations with rheology and atomic force microscopy experiments and highlighting the leading role of divalent cations. These results pave the way for future use of gellan-based systems in a variety of applications, from food science to art restoration

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA &lt; 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged &gt; 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p &lt; 0.001]. By multivariate analysis, females (p &lt; 0.01) and PWID (p &lt; 0.001), presented a longer time to ART initiation, while older people (p &lt; 0.001), people with higher educational levels (p &lt; 0.001), unemployed (p = 0.02) and students (p &lt; 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability

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

Monica Airoldi1,6, Mauro Zaccarelli2, Luca Bisi3, Teresa Bini4, Andrea Antinori2, Cristina Mussini3, Francesca Bai4, Giancarlo Orofino5, Laura Sighinolfi7, Andrea Gori6, Fredy Suter1, Franco Maggiolo11Division of Infectious Diseases, Ospedali Riuniti, Bergamo; 2Clinical Department, INMI L Spallanzani, Roma; 3Division of Infectious Diseases, Universit&amp;agrave;, Modena; 4Division of Infectious Diseases, Ospedale San Paolo, Milano; 5Division of Infectious Diseases, Ospedale Amedeo di Savoia, Torino; 6Division of Infectious Diseases, Ospedale San Gerardo, Monza; 7Division of Infectious Diseases, Ospedale Sant&amp;rsquo;Anna, Ferrara, ItalyObjective: 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 &amp;lt; 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 &amp;lt; 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 &amp;lt; 0.0001). QoL significantly influenced adherence&amp;nbsp;(P &amp;lt; 0.0001). During FDR use the mean CD4 count increased from 556 to 605 cells/&amp;mu;L (P &amp;lt; 0.0001). At the end of follow-up 98% of patients maintained HIV-RNA level &amp;lt; 50 copies/mL and 100% &amp;lt;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. Keywords: EFV/FTC/TDF, single-pill regimen, once-daily antiretroviral regimen, adherence, QoL, patient preference

Four-drugs regimen containing raltegravir is highly effective in HIV patients starting therapy with >500,000 copies/mL viral load

Introduction: Assessing virological response of four-drugs antiretroviral regimen that include raltegravir (RAL) in naïve patients with high viral load (>500,000 copies/mL) selected from a multicentre Italian database. Methods: Naïve patients with HIV RNA>500,000 copies/mL, who began standard antiretroviral regimens either based on non-nucleoside reverse transcriptase inhibitors (NNRTI) or boosted-PI (PI/r), or a standard regimen plus RAL between 2008 and 2013 were analyzed. Observation was censored at 12 months and the percentage of patients who achieved a viral load below the limit of detection (BLD) was calculated. Virological failure was defined as two consecutive viral loads>40 copies/mL. Results: Overall, 179 patients were included (13% with primary HIV infection (PHI), and 42.5% with AIDS diagnosis). Of them, 156 started standard three-drugs antiretroviral regimen (75.6% PI/r-based, 24.4% NNRTI-based. Among patients with PHI, 23 patients (12.8%), 6 (25%) started a four-drugs antiretroviral regimen containing both RAL and PI/r. Patients’ characteristics were as follows: males 74%, median age 42 years (IQR 35–51), sexually transmission 75.1%, median CD4 count 156 cells/µL (IQR 47–368) and median HIV-RNA 6.1 log10 copies/mL (IQR 5.8–6.4). 91 of 179 patients (50.8%) reached BLD viral load during the twelve months of observation. Three patients (1.7%) who began regimens PI/r-based with three-drugs had virological rebound after reaching BLD viral load. By use of survival analysis, we show that those patients who added RAL to the standard regimen have reached the primary end point faster (mean 8.4 months (95% CI 7.2–9.6) vs 11.4 (95% CI 11.0–11.8) in PI group and 10.3 (95% CI 9.4–11.1) in NNRTI group; p<0.001, Figure 1). In the adjusted analysis, the choice of a standard regimen versus a four-drugs regimen was driven only by higher baseline viral load (OR. 9.05; 95% CI 2.41–37.41; p=0.001). Conclusions: Only half of the naïve patients who began antiretroviral therapy having >500,000 copies/mL HIV-RNA had virological success at 12 months. The success was reached faster using the RAL-containing four-drugs regimen, suggesting that strengthening the initial regimen could be an option in patients with very high viral load to improve virological response

Suitability of energy cone for probabilistic volcanic hazard assessment: validation tests at Somma-Vesuvius and Campi Flegrei (Italy)

Pyroclastic density currents (PDCs) are gravity-driven hot mixtures of gas and volcanic particles which can propagate at high speed and cover distances up to several tens of kilometers around a given volcano. Therefore, they pose a severe hazard to the surroundings of explosive volcanoes able to produce such phenomena. Despite this threat, probabilistic volcanic hazard assessment (PVHA) of PDCs is still in an early stage of development. PVHA is rooted in the quantification of the large uncertainties (aleatory and epistemic) which characterize volcanic hazard analyses. This quantification typically requires a big dataset of hazard footprints obtained from numerical simulations of the physical process. For PDCs, numerical models range from very sophisticated (not useful for PVHA because of their very long runtimes) to very simple models (criticized because of their highly simplified physics). We present here a systematic and robust validation testing of a simple PDC model, the energy cone (EC), to unravel whether it can be applied to PVHA of PDCs. Using past PDC deposits at Somma-Vesuvius and Campi Flegrei (Italy), we assess the ability of EC to capture the values and variability in some relevant variables for hazard assessment, i.e., area of PDC invasion and maximum runout. In terms of area of invasion, the highest Jaccard coefficients range from 0.33 to 0.86 which indicates an equal or better performance compared to other volcanic mass-flow models. The p values for the observed maximum runouts vary from 0.003 to 0.44. Finally, the frequencies of PDC arrival computed from the EC are similar to those determined from the spatial distribution of past PDC deposits, with high PDC-arrival frequencies over an ∼8-km radius from the crater area at Somma-Vesuvius and around the Astroni crater at Campi Flegrei. The insights derived from our validation tests seem to indicate that the EC is a suitable candidate to compute PVHA of PDCs

Uncertainty Assessment of Pyroclastic Density Currents Uncertainty Assessment of Pyroclastic Density Currents Cone Model

Pyroclastic density currents (PDCs) are extremely dangerous phenomena so their modeling is essential for haz­ ard and risk purposes. However, PDCs are governed by very complex processes, making their deterministic prediction impossible. Probabilistic approaches are in a pioneering phase and feature large (and still unknown) uncertainties, from the natural variability of PDCs (aleatory uncertainty) to the main sources of epistemic uncertainty (input, parametric, theoretical and structural). In this chapter, we quantify these uncertainties by using the Energy Cone Model (ECM) in a Monte Carlo scheme applied to Mount Vesuvius. According to our results, theoretical uncertainty has the largest impact, 5 to 100 times bigger than input uncertainty, which seems to play a minor role. We find that conditional probabilities of PDC arrival (given an eruption of a specific size) show spatial distributions related to the surrounding topography. In particular, for medium and large eruptions, the conditional probability of PDCs traveling beyond Mount Somma is 1%–15% and 50%–60%, while they reach the Napoli airport in about 0%–1% and 0%–15% of the simulations, respectively. Small‐eruption PDCs remain restricted to the south flank and summit area. These results may guide future research devoted to reduce epistemic uncertainties and improve volcanic hazard analyses associated with PDCs.Published126-1451VV. Altr

Uncertainty Assessment of Pyroclastic Density Currents at Mount Vesuvius (Italy) Simulated Through the Energy Cone Model

Pyroclastic density currents (PDCs) are extremely dangerous phenomena so their modeling is essential for hazard and risk purposes. However, PDCs are governed by very complex processes, making their deterministic prediction impossible. Probabilistic approaches are in a pioneering phase and feature large (and still unknown) uncertainties, from the natural variability of PDCs (aleatory uncertainty) to the main sources of epistemic uncertainty (input, parametric, theoretical and structural). In this chapter, we quantify these uncertainties by using the Energy Cone Model (ECM) in a Monte Carlo scheme applied to Mount Vesuvius. According to our results, theoretical uncertainty has the largest impact, 5 to 100 times bigger than input uncertainty, which seems to play a minor role. We find that conditional probabilities of PDC arrival (given an eruption of a specific size) show spatial distributions related to the surrounding topography. In particular, for medium and large eruptions, the conditional probability of PDCs traveling beyond Mount Somma is 1%–15% and 50%–60%, while they reach the Napoli airport in about 0%–1% and 0%–15% of the simulations, respectively. Small‐eruption PDCs remain restricted to the south flank and summit area. These results may guide future research devoted to reduce epistemic uncertainties and improve volcanic hazard analyses associated with PDCs