Darcy's law of yield stress fluids on a treelike network.

Understanding the flow of yield stress fluids in porous media is a major challenge. In particular, experiments and extensive numerical simulations report a nonlinear Darcy law as a function of the pressure gradient. In this letter we consider a treelike porous structure for which the problem of the flow can be resolved exactly due to a mapping with the directed polymer (DP) with disordered bond energies on the Cayley tree. Our results confirm the nonlinear behavior of the flow and expresses its full pressure dependence via the density of low-energy paths of DP restricted to vanishing overlap. These universal predictions are confirmed by extensive numerical simulations.

Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.

Promising High-Tech Devices in Dry Eye Disease Diagnosis.

BACKGROUND: Dry eye disease (DED) is a common and debilitating condition that affects millions of people worldwide. Despite its prevalence, the diagnosis and management of DED can be challenging, as the condition is multifactorial and symptoms can be nonspecific. In recent years, there have been significant advancements in diagnostic technology for DED, including the development of several new devices. METHODS: A literature review of articles on the dry eye syndrome and innovative diagnostic devices was carried out to provide an overview of some of the current high-tech diagnostic tools for DED, specifically focusing on the TearLab Osmolarity System, DEvice Hygrometer, IDRA, Tearcheck, Keratograph 5M, Cornea Dome Lens Imaging System, I-PEN Osmolarity System, LipiView II interferometer, LacryDiag Ocular Surface Analyzer, Tearscope-Plus, and Cobra HD Camera. CONCLUSIONS: Despite the fact that consistent use of these tools in clinical settings could facilitate diagnosis, no diagnostic device can replace the TFOS algorithm.

Many-Body Quantum Chaos and Emergence of Ginibre Ensemble.

We show that non-Hermitian Ginibre random matrix behaviors emerge in spatially extended many-body quantum chaotic systems in the space direction, just as Hermitian random matrix behaviors emerge in chaotic systems in the time direction. Starting with translational invariant models, which can be associated with dual transfer matrices with complex-valued spectra, we show that the linear ramp of the spectral form factor necessitates that the dual spectra have nontrivial correlations, which in fact fall under the universality class of the Ginibre ensemble, demonstrated by computing the level spacing distribution and the dissipative spectral form factor. As a result of this connection, the exact spectral form factor for the Ginibre ensemble can be used to universally describe the spectral form factor for translational invariant many-body quantum chaotic systems in the scaling limit where t and L are large, while the ratio between L and L_{Th}, the many-body Thouless length is fixed. With appropriate variations of Ginibre models, we analytically demonstrate that our claim generalizes to models without translational invariance as well. The emergence of the Ginibre ensemble is a genuine consequence of the strongly interacting and spatially extended nature of the quantum chaotic systems we consider, unlike the traditional emergence of Hermitian random matrix ensembles.

Real Life Impact of Dry Eye Disease.

Dry Eye Disease (DED) is an increasingly common condition that affects between 5% and 50% of the global population. Even though DED is most frequently diagnosed in older people, it has also been diagnosed in young adults and adolescents more frequently in recent years (employees, gamers). People can experience different types of symptoms and find it challenging to read, watch TV, cook, climb stairs, and meet friends. Mild and severe dry eye can reduce quality of life similarly to mild psoriasis and moderate-to-severe angina. Furthermore, DED patients experience serious difficulties driving vehicles, especially at night, and show a decrease in work productivity, which, when combined with the relevant indirect cost that this condition produces, poses a serious challenge in our days. In addition, DED patients are more likely to develop depression and suicidal ideations and experience frequent sleep disorders. Finally, it is discussed how lifestyle changes, such as increased physical activity, blinking exercises, and a proper diet, have positive implications for the management of this condition. Our aim is to draw attention to the negative effects of dry eye in real life, which are unique to each patient, especially as they relate to the non-visual symptoms experienced by DED patients.

Many-body quantum chaos and space-time translational invariance.

We study the consequences of having translational invariance in space and time in many-body quantum chaotic systems. We consider ensembles of random quantum circuits as minimal models of translational invariant many-body quantum chaotic systems. We evaluate the spectral form factor as a sum over many-body Feynman diagrams in the limit of large local Hilbert space dimension q. At sufficiently large t, diagrams corresponding to rigid translations dominate, reproducing the random matrix theory (RMT) behaviour. At finite t, we show that translational invariance introduces additional mechanisms via two novel Feynman diagrams which delay the emergence of RMT. Our analytics suggests the existence of exact scaling forms which describe the approach to RMT behavior in the scaling limit where both t and L are large while the ratio between L and LTh(t), the many-body Thouless length, is fixed. We numerically demonstrate, with simulations of two distinct circuit models, that the resulting scaling functions are universal in the scaling limit.

New Approach to Privacy-Preserving Clinical Decision Support Systems for HIV Treatment.

BACKGROUND: HIV treatment prescription is a complex process. Clinical decision support systems (CDSS) are a category of health information technologies that can assist clinicians to choose optimal treatments based on clinical trials and expert knowledge. The usability of some CDSSs for HIV treatment would be significantly improved by using the knowledge obtained by treating other patients. This knowledge, however, is mainly contained in patient records, whose usage is restricted due to privacy and confidentiality constraints. METHODS: A treatment effectiveness measure, containing valuable information for HIV treatment prescription, was defined and a method to extract this measure from patient records was developed. This method uses an advanced cryptographic technology, known as secure Multiparty Computation (henceforth referred to as MPC), to preserve the privacy of the patient records and the confidentiality of the clinicians' decisions. FINDINGS: Our solution enables to compute an effectiveness measure of an HIV treatment, the average time-to-treatment-failure, while preserving privacy. Experimental results show that our solution, although at proof-of-concept stage, has good efficiency and provides a result to a query within 24 min for a dataset of realistic size. INTERPRETATION: This paper presents a novel and efficient approach HIV clinical decision support systems, that harnesses the potential and insights acquired from treatment data, while preserving the privacy of patient records and the confidentiality of clinician decisions.

Dynamics of Total and Intact HIV-1 DNA in Virologically Suppressed Patients Switching to DTG-Based or ATV-Based Dual Therapy.

BACKGROUND: Clinical trials have demonstrated noninferior viral suppression rates of selected 2-drug regimens (2DRs) over standard 3-drug regimens (3DRs). However, the effect of simplification to 2DRs on HIV-1 reservoir remains to be fully assessed. SETTING: Retrospective analyses of samples of virologically suppressed people living with HIV remaining on the same 3DRs or switching to DTG + 3TC or ATV/r + 3TC 2DRs. METHODS: Whole blood samples were collected at enrollment and after 48 weeks. Total HIV-1 DNA (tDNA) and intact HIV-1 DNA (iDNA) were quantified by droplet digital polymerase chain reaction and intact proviral DNA assay, respectively. Statistical analysis was performed to identify associations among variables, and multiple linear regression was used to analyze potential predictors of tDNA and iDNA changes over time. RESULTS: Forty-seven individuals were switched to DTG + 3TC 2DR (N = 23) and ATV/r + 3TC 2DR (N = 24), while 18 remained on 3DRs. tDNA did not change either in the overall population or in the 3DR and 2DR groups. iDNA decreased significantly in the whole data set and in the overall 3DR and 2DR groups ( P = 0.001, P = 0.039 and P = 0.009, respectively). iDNA, but not tDNA, was inversely correlated with the time of viral suppression ( P = 0.002) and time under antiretroviral therapy ( P = 0.006). Higher nadir CD4 + T-cell counts ( P = 0.001) and lower zenith viral load ( P = 0.02) showed an association with the decrease of iDNA, but not with tDNA. CONCLUSIONS: Both tDNA and iDNA dynamics supported noninferior efficacy of 2DRs over 3DRs. iDNA could be more informative than tDNA in analyzing the dynamics of the HIV-1 reservoir under different treatment strategies.

A highly stable, nanotube-enhanced, CMOS-MEMS thermal emitter for mid-IR gas sensing.

The gas sensor market is growing fast, driven by many socioeconomic and industrial factors. Mid-infrared (MIR) gas sensors offer excellent performance for an increasing number of sensing applications in healthcare, smart homes, and the automotive sector. Having access to low-cost, miniaturized, energy efficient light sources is of critical importance for the monolithic integration of MIR sensors. Here, we present an on-chip broadband thermal MIR source fabricated by combining a complementary metal oxide semiconductor (CMOS) micro-hotplate with a dielectric-encapsulated carbon nanotube (CNT) blackbody layer. The micro-hotplate was used during fabrication as a micro-reactor to facilitate high temperature (>700 [Formula: see text]C) growth of the CNT layer and also for post-growth thermal annealing. We demonstrate, for the first time, stable extended operation in air of devices with a dielectric-encapsulated CNT layer at heater temperatures above 600 [Formula: see text]C. The demonstrated devices exhibit almost unitary emissivity across the entire MIR spectrum, offering an ideal solution for low-cost, highly-integrated MIR spectroscopy for the Internet of Things.

Durability of rilpivirine-based versus integrase inhibitor-based regimens in a large cohort of naïve HIV-infected patients starting antiretroviral therapy.

OBJECTIVES: Comparisons between rilpivirine (RPV) and integrase strand transfer inhibitors (INSTIs) in antiretroviral therapy (ART)-naïve HIV-infected individuals are currently lacking. This study aimed to compare, in an observational cohort setting, the durability of treatment with RPV-based and INSTI-based first-line regimens. METHODS: Patients who started first-line ARTs based on RPV or INSTIs, with HIV-RNA < 100 000 copies/mL and CD4 cell count > 200 cells/µL were included. The primary endpoint was the cumulative probability of treatment failure (TF = virological failure [confirmed HIV-RNA > 50 copies/mL] or discontinuation of the anchor drug in the regimen), as assessed by the Kaplan-Meier method. A multivariable Cox regression was used to control for potential confounding. RESULTS: Of the 1991 included patients, 986 started ART with an RPV-based regimen and 1005 with an INSTIs-based regimen. The median (IQR) follow-up was 20 (10, 35) months. The cumulative 2-year probability of TF with RPV (9.1% [95% 7.2, 11.1]) was lower than that observed in the INSTIs group (16.6% [13.8, 19.4], P = 0.0002) but not when compared with dolutegravir (DTG) alone. Starting ART with an INSTIs-based regimen vs. RPV was associated with a higher risk of TF after controlling for potential confounding factors (adjusted hazard ratio, AHR [95% CI]: 1.64 [1.28, 2.10]; P < 0.001). The results were similar when restricting the analysis to single-tablet regimens, although the probability of virological success was higher for INSTIs and DTG. CONCLUSIONS: In ART-naïve patients with low viral loads and high CD4 counts, the risk of treatment failure was lower in those who started RPV-based vs. INSTIs-based regimens other than DTG-based ones.

Hepatitis C Virus Core Antigen (HCVAg): an affordable assay to monitor the efficacy of treatment in DAAs era.

Hepatitis C virus (HCV) Core Antigen (HCVAg) and HCV-RNA were tested in 962 plasma/serum samples from 180 patients during Direct Antiviral Agents (DAAs) treatment and at follow-up. One hundred and eighty individuals were included: 71% carried advanced fibrosis and 43% were treatment-experienced. A Sustained Virological Response (SVR) was achieved in 166/180 (92%) individuals: 96/102 (94.1%) na ve and 70/78 (89.7%) treatment-experienced (p=0.20). The baseline median levels of HCV-RNA and HCVAg were not significantly different between individuals achieving SVR (5.92 x 105 IU/mL, IQR 5.4-6.4, and 3,417 fmol/L, 2,900-3,795) and those without SVR (6.06 x 105 IU/mL, 5.63-6.57, and 3,391 fmol/L, 2,828-4,077). The HCV-RNA vs. HCVAg assays results showed a fair correlation with an overall moderate qualitative agreement (kappa=0.52). Among treatment-failed individuals, at failure 100% of the assays results were positive for both techniques, with HCV-RNA median value 3.09 x 105 IU/mL (2.10-29.09) and HCVAg median value 1570.28 fmol/L (360.15-9317.67). Undetectable HCV-RNA at EOT showed sensitivity 54%, specificity 100%, negative predictive value (NPV) 93% and positive predictive value (PPV) 100%. Undetectable HCVAg at EOT showed sensitivity 74%, specificity 100%, NPV 97% and PPV 100%. The operative and economic advantages of the HCVAg support the alternative use of HCVAg to monitor DAAs treatment outcome.

Maraviroc as a potential HIV-1 latency-reversing agent in cell line models and ex vivo CD4 T cells.

Recent studies have suggested that the CCR5 antagonist maraviroc (MVC) may exert an HIV-1 latency reversal effect. This study aimed at defining MVC-mediated induction of HIV-1 in three cell line latency models and in ex vivo CD4 T cells from six patients with suppressed viraemia. HIV-1 induction was evaluated in TZM-bl cells by measuring HIV-1 LTR-driven luciferase expression, and in ACH-2 and U1 latently infected cell lines by measuring cell-free (CFR) and cell-associated (CAR) HIV-1 RNA by qPCR. NF-κB p65 was quantified in nuclear extracts by immunodetection. In ex vivo CD4 T cells, CAR, CFR and cell-associated DNA (CAD) were quantified at baseline and 1-7-14 days post-induction (T1, T7, T14). At T7 and T14, the infectivity of the CD4 T cells co-cultured with MOLT-4/CCR5 target cells was evaluated in the TZM-bl assay (TZA). Results were expressed as fold activation (FA) with respect to untreated cells. No LTR activation was observed in TZM-bl cells at any MVC concentration. NF-κB activation was only modestly upregulated (1.6±0.4) in TZM-bl cells with 5 µM MVC. Significant FA of HIV-1 expression was only detected at 80 µM MVC, namely on HIV-1 CFR in U1 (3.1±0.9; P=0.034) and ACH-2 cells (3.9±1.4; P=0.037). CFR was only weakly stimulated at 20 µM in ACH-2 (1.7±1.0 FA) cells and at 5 µM in U1 cells (1.9±0.5 FA). Although no consistent pattern of MVC-mediated activation was observed in ex vivo experiments, substantial FA values were detected sparsely on individual samples with different parameters. Notably, in one sample, MVC stimulated all parameters at T7 (2.3±0.2 CAD, 6.8±3.7 CAR, 18.7±16.7 CFR, 7.3±0.2 TZA). In conclusion, MVC variably induces HIV-1 production in some cell line models not previously used to test its latency reversal potential. In ex vivo CD4 T cells, MVC may exert patient-specific HIV-1 induction; however, clinically relevant patterns, if any, remain to be defined.

Ambulatory blood pressure and risk of new-onset atrial fibrillation in treated hypertensive patients.

The aim of this study was to evaluate the influence of clinic and ambulatory blood pressure (BP) on the occurrence of new-onset atrial fibrillation (AF) in treated hypertensive patients. We studied 2135 sequential treated hypertensive patients aged >40 years. During the follow-up (mean 9.7 years, range 0.4-20 years), 116 events (new-onset AF) occurred. In univariate analysis, clinic, daytime, nighttime, and 24-h systolic BP were all significantly associated with increased risk of new-onset AF, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.22 (1.11-1.35), 1.36 (1.21-1.53), 1.42 (1.29-1.57), and 1.42 (1.26-1.60), respectively. After adjustment for various covariates in multivariate analysis, clinic systolic BP was no longer associated with increased risk of new-onset AF, whereas daytime, nighttime, and 24-h systolic BP remained significantly associated with outcome, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.09 (0.97-1.23), 1.23 (1.10-1.39), 1.16 (1.03-1.31), and 1.22 (1.06-1.40), respectively. Daytime, nighttime, and 24-h systolic BP are superior to clinic systolic BP in predicting new-onset AF in treated hypertensive patients. Future studies are needed to evaluate whether a better control of ambulatory BP might be helpful in reducing the occurrence of new-onset AF.

Analysis of genetic and viral determinants of HBsAg levels in patients with chronic HBV infection.

Single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) gene can influence the course of treated and untreated HBV infection. However, the correlation between different IL28B-SNPs and HBVDNA and quantitative HBsAg (qHBsAg) in chronic HBV infection remains to be fully elucidated. Patients with chronic HBV infection were analysed for qHBsAg, HBVDNA, HBV genotype and six IL28B-SNPs (rs12980275, rs8105790, rs8099917, rs7248668, rs12979860, rs10853728). Seventy patients were recruited: 80% Caucasian, 56% genotype D, 44% treated with nucleos(t)ide analogues, 11% cirrhotic, 37% inactive carriers (IC). Median (IQR) qHBsAg and HBVDNA were 3.2 log10 IU/ml (2.2-3.9) and 2.2 log10 IU/ml (0.3-3.3), respectively. Lower levels of qHBsAg were associated in the whole study population with rs12979860 CC vs. CT (p=0.05), rs12980275 AA vs. AG (p=0.04), rs8105790 TT vs. CT (p=0.05) and genotype D vs. A+E (p=0.01). rs8105790 TT was present in 81% of IC vs. 46% non-IC (p=0.005). These data were also confirmed in the untreated patients' subgroup. In multivariate analysis, IL28B-SNP haplogroups were associated with lower qHBsAg: CC/AA at rs12979860/rs12980275 (-0.70 log IU/mL, 95% CI -1.26;-0.14; p=0.01), CC/TT at rs12979860/rs8105790 (-0.78 log IU/mL, 95% CI -1.33;-0.23; p=0.006) and AA/TT at rs12980275/rs8105790 (-0.71 log IU/mL, 95% CI -1.27;-0.17; p=0.01) both in the whole population and in the untreated subgroup. Specific IL28-SNP haplogroups might be associated with lower qHBsAg.

Thermalization of a Trapped One-Dimensional Bose Gas via Diffusion.

For a decade the fate of a one-dimensional gas of interacting bosons in an external trapping potential remained mysterious. We here show that whenever the underlying integrability of the gas is broken by the presence of the external potential, the inevitable diffusive rearrangements between the quasiparticles, quantified by the diffusion constants of the gas, eventually lead the system to thermalize at late times. We show that the full thermalizing dynamics can be described by the generalized hydrodynamics with diffusion and force terms, and we compare these predictions to numerical simulations. Finally, we provide an explanation for the slow thermalization rates observed in numerical and experimental settings: the hydrodynamics of integrable models is characterized by a continuity of modes, which can have arbitrarily small diffusion coefficients. As a consequence, the approach to thermalization can display prethermal plateau and relaxation dynamics with long polynomial finite-time corrections.

Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors.

OBJECTIVES: This study evaluated the emergence of mutations associated with integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in human immunodeficiency virus type 1 (HIV-1) infected patients treated with this drug class. METHODS: The emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under INSTI treatment and before INSTI treatment) were evaluated in 107 INSTI-naïve patients (19 drug-naïve and 88 drug-experienced) with two plasma genotypic resistance tests: one before INSTI treatment and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associated with the integrase evolution under INSTI treatment. RESULTS: The patients were mainly infected by B subtype (72.0%). Eighty-seven patients were treated with raltegravir, 13 with dolutegravir and seven with elvitegravir. Before INSTI treatment one patient harboured the major INSTI-RM R263K and three patients the accessory INSTI-RMs T97A. Under INSTI treatment the emergence of ≥1 INSTI-RM was found in 39 (36.4%) patients. The major INSTI-RMs that more frequently emerged were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), and Y143C (4.7%). Concerning integrase evolution, a higher genetic distance was found in patients with ≥1 INSTI-RM compared with those without emergence of resistance (0.024 [0.012-0.036] vs. 0.015 [0.009-0.024], P=0.018). This higher integrase evolution was significantly associated with a longer duration of HIV-1 infection, a higher number of past regimens and non-B subtypes. CONCLUSIONS: These findings confirm that major INSTI-RMs very rarely occur in INSTI-naïve patients. Under INSTI treatment, selection of drug-resistance follows the typical drug-resistance pathways; a higher evolution characterises integrase sequences developing drug-resistance compared with those without any resistance.

Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study.

BACKGROUND: Antiretroviral drug resistance mutations remain a major cause of treatment failure. OBJECTIVES: To evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens. MATERIALS AND METHODS: We selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of >50 copies/mL. RESULTS: We included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39-53), 7 years (3-16) of HIV infection, nadir CD4+ 247 cells/mm3 (105-361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3-12.5) versus 3.8% (2.1-5.5) in virologically suppressed patients and 66.7% (39.5-93.9) versus 11.2% (6.5-15.9) (P<0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02-1.27, P=0.024) in viraemic patients. CONCLUSIONS: A switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term.

Spectral Statistics and Many-Body Quantum Chaos with Conserved Charge.

We investigate spectral statistics in spatially extended, chaotic many-body quantum systems with a conserved charge. We compute the spectral form factor K(t) analytically for a minimal Floquet circuit model that has a U(1) symmetry encoded via spin-1/2 degrees of freedom. Averaging over an ensemble of realizations, we relate K(t) to a partition function for the spins, given by a Trotterization of the spin-1/2 Heisenberg ferromagnet. Using Bethe ansatz techniques, we extract the "Thouless time" t_{Th} demarcating the extent of random matrix behavior, and find scaling behavior governed by diffusion for K(t) at t≲t_{Th}. We also report numerical results for K(t) in a generic Floquet spin model, which are consistent with these analytic predictions.

Clinical use, efficacy, and durability of maraviroc for antiretroviral therapy in routine care: A European survey.

OBJECTIVES: The study aimed to survey maraviroc use and assess effectiveness and durability of maraviroc-containing antiretroviral treatment (ART) in routine practice across Europe. METHODS: Data were retrieved from 26 cohorts in 8 countries comprising adults who started maraviroc in 2005-2016 and had ≥1 follow-up visit. Available V3 sequences were re-analysed centrally for tropism determination by geno2pheno[coreceptor]. Treatment failure (TF) was defined as either virological failure (viral load >50 copies/mL) or maraviroc discontinuation for any reason over 48 weeks. Predictors of TF were explored by logistic regression analysis. Time to maraviroc discontinuation was estimated by Kaplan-Meier survival analysis. RESULTS: At maraviroc initiation (baseline), among 1,381 patients, 67.1% had experienced ≥3 ART classes and 45.6% had a viral load <50 copies/mL. Maraviroc was occasionally added to the existing regimen as a single agent (7.3%) but it was more commonly introduced alongside other new agents, and was often (70.4%) used with protease inhibitors. Accompanying drugs comprised 1 (40.2%), 2 (48.6%) or ≥3 (11.2%) ART classes. Among 1,273 patients with available tropism data, 17.6% showed non-R5 virus. Non-standard maraviroc use also comprised reported once daily dosing (20.0%) and a total daily dose of 150mg (12.1%). Over 48 weeks, 41.4% of patients met the definition of TF, although the 1-year estimated retention on maraviroc was 82.1% (95% confidence interval 79.9-84.2). Among 1,010 subjects on maraviroc at week 48, the viral load was >50 copies/mL in 19.9% and >200 copies/mL in 10.7%. Independent predictors of TF comprised a low nadir CD4 count, a detectable baseline viral load, previous PI experience, non-R5 tropism, having ≥3 active drugs in the accompanying regimen, and a more recent calendar year of maraviroc initiation. CONCLUSIONS: This study reports on the largest observation cohort of patients who started maraviroc across 8 European countries. In this overall highly treatment-experienced population, with a small but appreciable subset that received maraviroc outside of standard treatment guidelines, maraviroc was safe and reasonably effective, with relatively low rates of discontinuation over 48 weeks and only 2 cases of serum transaminase elevations reported as reasons for discontinuation.