Search

Background Bacterial co-infections in COVID-19 patients represent a significant challenge for clinicians and can impact outcomes. Rapid identification of bacterial co-pathogens improves management, and is crucial to avoid inappropriately administered antimicrobials. We evaluated the use of a multiplex PCR assay in the early detection of respiratory co-infections in COVID-19 hospitalized patients. Methods The study included non-ICU patients with high clinical suspicion of respiratory co-infection. Lower respiratory tract samples (sputum/bronchial secretions), were analyzed using BIOFIRE® FILMARRAY® pneumonia panel plus [(bioMerieux, USA), FA]. Specimens were considered as acceptable based on Gram stain. Conventional cultures were also performed. Results A total of 28 samples from 27 patients (20 males, median age 60 years, IQR 49-71) were analyzed. 8/27 patients were intubated, 5 were treated with high flow nasal canula oxygenation and 11 with high or low oxygen mask. 18 patients received dexamethasone. Co-infection was detected in 17/27 patients (62.9%). 11 specimens were collected in less than 48 hours from admission and no target was identified in 6/11. Detected pathogens and AMR genes, per sample tested, are presented in the table. Bacterial pathogens and any AMR genes were detected in 15 and 4 samples, respectively, leading to modifications of antimicrobial treatment. The semi-quantitative results along with patients’ clinical presentation assisted with differentiation of bacterial colonization versus infection, especially in cases where multiple targets were identified. De-escalation was implemented for 12 patients, for whom no co-infection or a viral co-pathogen (n=2) was detected. One patient was co-infected with another Coronavirus; further analysis, using the FA respiratory panel, detected Human coronavirus HKU-1 along with SARS-CoV-2. Median time until discharge or death was 13.5 days (IQR 9-24). Overall mortality was 33.3%. Detected pathogens, microbial load and AMR genes, per sample tested. Conclusion Implementation of FA assay proved effective for the rapid detection of respiratory co-infections in COVID-19 non-ICU patients. Molecular panel-based assays can contribute to timely adaptation of antimicrobial treatment, benefiting patient management and antibiotic stewardship strategies. Disclosures All Authors: No reported disclosures.

OBJECTIVE To propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages. DESIGN The established 90-90-90 target follows a cross-sectional 4-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation and viral suppression (VS) durability. METHODS Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people living with HIV (PLHIV) by estimated time from infection to diagnosis; of those who ever initiated ΑRT or achieved VS by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and VS, treating loss-to-follow-up (LTFU) as competing event. VS was defined as viral load (VL)

The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes.This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949).Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22-0.50; CCI2, OR: 0.38, 95% CI 0.21-0.68; suPAR9 ng/mL, OR: 0.35, 95% CI 0.19-0.66; suPAR 6-9 ng/mL, OR: 0.35, 95% CI 0.24-0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25-0.66; and patients65 years, OR: 0.29, 95% CI 0.19-0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28-0.57) and 0.46 (95% CI 0.32-0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment.Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90.Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB.

HIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis.Our nationwide sample included HIV-1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999-2015. Our analysis was based on the molecularly inferred HIV-1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B.Analysis of the determinants of LP was conducted using either CD4 counts or AIDS-defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age-dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks.We demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations.

Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear. Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis. Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization. Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8–13.1%; 9/125) versus 15.3% (95% CI, 10.1–22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20–0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10–22.5%; 19/125) versus 28.2% (95% CI, 21.2–36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29–0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5–7) versus 10 (range, 7–15) days (P

Contains fulltext : 237989.pdf (Publisher’s version ) (Closed access) BACKGROUND: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. METHODS: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). FINDINGS: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO(2)/FiO(2)), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO(2)/FiO(2). In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]). INTERPRETATION: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. FUNDING: Sobi.

Background Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. Objectives To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). Methods A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. Results One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. Conclusions Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

ObjectivesSubtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions.MethodsOur analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window.ResultsA significant decline was detected for the treatment window during 2014–2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval.ConclusionsOur findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.

The aim of this study was to propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages.The established 90-90-90 target follows a cross-sectional four-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation, and viral suppression durability.Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people with HIV (PWH) by estimated time from infection to diagnosis; of those who ever initiated ART or achieved viral suppression by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and viral suppression, treating loss-to-follow-up (LTFU) as competing event. Viral suppression was defined as viral load less than 500 copies/ml. Viral suppression durability was assessed by the CIF of viral load rebound.About 89.1% of PWH in 2018 were diagnosed (range of diagnoses: 1980-2018). Median time to diagnosis was 3.5 years (IQR: 1.1-7.0). Among diagnosed, 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9 and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved viral suppression, of whom 87.4% were currently virally suppressed. The CIF of viral load rebound was 24.2% at 5 years since first viral suppression but substantially reduced in more recent years.The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC.

Early recognition of risk and start of treatment may improve unfavorable outcome of COVID-19. In the SAVE-MORE double-blind randomized trial, 594 patients with pneumonia without respiratory dysfunction at risk as defined by plasma suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml were 1:2 randomized to subcutaneous placebo or 100 mg anakinra once daily for 10 days; 85.9% were co-administered dexamethasone. After 28 days, anakinra-treated patients were distributed to lower strata of the 11-point World Health Organization ordinal Clinical Progression Scale (WHO-CPS) (adjusted odds ratio-OR 0.36; 95%CI 0.26–0.50; P

BackgroundIn a previous open-label trial, early anakinra treatment guided by elevated soluble urokinase plasminogen activator receptor (suPAR) prevented progression of COVID-19 pneumonia into respiratory failure.MethodsIn the SAVE-MORE multicenter trial, 594 hospitalized patients with moderate and severe COVID-19 pneumonia and plasma suPAR 6 ng/ml or more and receiving standard-of-care were 1:2 randomized to subcutaneous treatment with placebo or 100 mg anakinra once daily for 10 days. The primary endpoint was the overall clinical status of the 11-point World Health Organization ordinal Clinical Progression Scale (WHO-CPS) at day 28. The changes of the WHO-CPS and of the sequential organ failure assessment (SOFA) score were the main secondary endpoints.ResultsAnakinra-treated patients were distributed to lower strata of WHO-CPS by day 28 (adjusted odds ratio-OR 0.36; 95%CI 0.26-0.50; PConclusionsEarly start of anakinra treatment guided by suPAR provides 2.78 times better improvement of overall clinical status in moderate and severe COVID-19 pneumonia.(Sponsored by the Hellenic Institute for the Study of SepsisClinicalTrials.govidentifier,NCT04680949)

Background Antimicrobial resistance (AMR) is an increasing threat to public health and antimicrobial consumption is a primary driver of resistance. Many studies have shown that the implementation of an antibiotic stewardship program (ASP) improves prescribing of antibiotics and can reduce AMR. Purpose of the study was to assess the impact of a successful ASP, implemented for four years, on AMR in our 427-bed tertiary general hospital. Methods We monitored pharmacy data for the years 2015 (pre-intervention) and 2016-2019 (post-intervention) for antibiotic consumption (DDD/100 bed-days) and resistance rates. AMR data were obtained from the clinical microbiology laboratory’s electronic database. To achieve the goals of ASP we used a range of interventions as pre-authorization strategy for the protected antibiotics (tigecycline, carbapenems, quinolones, glycopeptides, daptomycin, colistin, linezolid), prospective audit and feedback with direct intervention, de-escalation or switch from iv to oral administration and appropriate selection and duration of chemoprophylaxis in surgery. Results Significant reductions were observed for: total antibiotics, colistin, carbapenems, quinolones and tigecycline consumption during study period. Significantly lower resistance rates were documented in 2019 compared to 2015 for Pseudomonas aeruginosa and for Klebsiella pneumoniae. As for Acinetobacter baumannii isolates, which in our hospital are highly-resistant exhibiting >90% resistance to carbapenems, no significant changes were noted during the study period. Infections caused by Gram-positive pathogens are less prevalent in our hospital. Lower rates of vancomycin-resistant enterococci were noted after the implementation of our ASP (30.4% in 2019 vs. 50.0% in 2015 for E. faecium and 0.6% vs. 6% for E. faecalis, respectively), whereas methicillin-resistant S. aureus isolates increased (40% in 2019 vs. 31.1% in 2015), possibly because most of these infections were not hospital-acquired. Resistance rates of Pseudomonas and Klebsiella Conclusion Our ASP was successful in reducing antibiotic consumption and AMR for important pathogens. Disclosures All Authors: No reported disclosures

This study aimed to investigate the effects of a 4-year antibiotic stewardship program (ASP) in a tertiary hospital. We monitored data for 2015 (pre-intervention) and 2016-2019 (post-intervention) about antibiotic consumption (DDD/100 bed days), Clostridioides difficile infections (CDIs), resistance rates, length of stay (LOS), and annual antibiotic costs. Significant reductions were observed for total antibiotics/colistin/carbapenems/quinolones/tigecycline consumption and resistance rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and vancomycin-resistant enterococci. Considerable reductions occurred for LOS (4.18 [2015]/3.0 [2019] days), CDIs (1.47 [2015]/0.86 [2019] per 1000 patients), antibiotic cost/patient (39.45€ [2015]/23.69€ [2019]). The ASP was successful in reducing antibiotic consumption, antibiotic costs, length of hospital stay, and CDIs.

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml−1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P, The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1α/β inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor.

Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2&ndash, 1518 subtype A1 sequences and 168 MTCs in the range of 2&ndash, 218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p &lt, 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p &lt, 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p &lt, 0.001), and more recent sampling (time period: 2011&ndash, 2015 vs. 1999&ndash, 2005, OR = 3.83, p &lt, 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention.

The aim of this study was to investigate the effect of the implementation of an antibiotic stewardship program (ASP) on antibiotic consumption in our 428-bed hospital. The Infection Control Committee implemented an ASP beginning in January 2016, aiming to reduce inappropriate antibiotic use through improved prescribing practices. The ASP included both pre-authorization and prospective audit and feedback strategies. We collected pharmacy and hospital data for the years 2015 (pre-intervention) and 2016 (post-intervention). Consumption data were expressed as daily defined doses (DDDs) per 100 patient-days (PD) and the significance of the differences between 2015 and 2016 was assessed by paired t-test. Antibiotic resistance rates for the most important hospital pathogens were monitored for 2015–2016. The ASP effectively reduced consumption of most antimicrobials; total antibiotic use decreased by 16.7% (from 104.3 in 2015 to 86.9 DDDs/100 patient-days in 2016, p

Objective Combined antiretroviral treatment (cART) results in profound immunologic improvement, but it is unclear whether CD4 cell counts return to levels similar to those of HIV-negative individuals. We explore long-term CD4 cell count evolution post-cART and its association with baseline levels, virologic suppression, pre-cART cumulative viremia and other factors. Design Data were derived from the AMACS. Included individuals were adults who started cART, at least 2003, while previously ART-naive. Methods Changes in CD4 cell counts were modeled through piecewise linear mixed models. Results A total of 3405 individuals were included. The majority was male (86.0%), homosexual (58.8%) with median (IQR) age at cART initiation 36 (31-44) years and a median (IQR) follow-up of 3.9 (2.0-6.9) years. Most persons (57%) starting cART with less than 200 cells/μl did not reach 600 cells/μl after 7 years of treatment. Those starting cART with 200-349 CD4 cells/μl could reach 600 cells/μl within less than 2 years of fully suppressive treatment. Probability of CD4 normalization (i.e. >800 cells/μl) after 7 years of suppressive treatment was 24 and 46% for those starting treatment with less than 200 or 200-349 CD4 cells/μl, respectively. Lower pre-cART cumulative viremia was associated with faster CD4 recovery. CD4 cell count increases after 4 years were either insignificant or very slow, irrespectively of baseline levels. Conclusion cART initiation before CD4 cell count drops below 350 cells/μl is crucial for achieving normal CD4 levels. These findings underline the importance of timely diagnosis and cART initiation as the risk of both AIDS and non-AIDS-related morbidity/mortality remains increased in patients with incomplete CD4 recovery.

The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the Re was >1 between 2008 and the first half of 2013. For all E138A LTNs, the Re was >1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was >1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health.

A matched 1:3 case-control study investigated factors predicting colistin-resistant versus colistin-susceptible KPC-producing Klebsiella pneumoniae acquisition and its impact on patient outcomes. Case patients were more often admitted from other institutions ( P = 0.019) and had longer therapy with β-lactam/β-lactamase inhibitors ( P = 0.002) and higher overall mortality ( P = 0.05). All 52 study isolates were clonally related, suggesting horizontal dissemination. None of these parameters independently predicted colistin resistance, which probably occurred in a susceptible KPC-KP strain that was subsequently disseminated horizontally.

Background: Chronic kidney disease (CKD) in HIV-infected patients is associated with both HIV and non-HIV-related factors. Initial renal dysfunction is silent and detectable only by laboratory tests such as the glomerular filtration rate (GFR) estimated by the Cockcroft-Gault equation. Our objective was to assess possible risk factors for CKD in a cohort of Greek HIV-1-infected adults. Methods: Patients in the AMACS (Athens Multicenter AIDS Cohort Study) cohort with at least two available creatinine values were enrolled in the study. Renal dysfunction was defined as eGFR below 90 mL/min/1.73 m 2 . The Kaplan-Meier estimator and the Cox proportional hazards model were used to analyze the occurrence and predictors of renal dysfunction. Results: A total of 1073 patients were enrolled in the study; 255 (23.76%) had baseline eGFR below 90 mL/min/1.73 m 2 and were excluded. Characteristics of the study population: men 88.4%, MSM 62.6%, median baseline age, CD4+ count and viral load were 32.6 years, 413 cells/μL and 3.77 log 10 copies/mL, respectively. 240 (29.3%) patients experienced an eGFR decrease below 90 mL/min/1.73 m 2 during follow-up period. Older age, female gender, heterosexual mode of transmission, lower baseline eGFR (all p

Introduction: The prevalence of drug resistance is approximately 10% in Europe and North America among newly infected patients. We aim to investigate the temporal patterns of resistance among drug naive HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains. Materials and Methods: Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 2499 newly diagnosed HIV-1 patients, in Greece, during 2003–2013. Genotypic drug resistance was estimated using the HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission clusters of resistant strains on the basis of a large collection of HIV-1 sequences from 4024 seropositives in Greece. Phylodynamic analysis was performed using a Bayesian method. Results: We estimated drug resistance levels among naive patients on the basis of all resistance mutations in PR and partial RT. The overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was the most common (397/2499, 15.9%) followed by PIs (116/2499, 4.6%) and NRTIs (79/2499, 3.2%). We found a significant trend for decreasing resistance to NRTIs over time (6.7%–1.6%). There was no time trend for the overall PI and NNRTI resistance. The most frequently observed major resistant sites in PR were V82 (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%), K103 (13.1%), V179 (8.4%) and T215 (7.1%), M41 (4.7%) associated with resistance to NNRTIs and NRTIs, respectively. The prevalence of K103N and E138Q were significantly increased during 2003–2013. Crucially, we found that both K103N, E138Q are associated with transmission networking within men having sex with men (MSM) and intravenous drug user (IDU) local networks. The K103N network included seropositives across Greece, while the latter only from the recent IDU outbreak in Athens metropolitan area [1]. Phylodynamic analyses revealed that the exponential growth for K103N network started in 2009 (Figure 1) and for the E138Q in 2010. Conclusions: The overall resistance has been stable in Greece over time; however, specific NNRTI resistance patterns are increasing. Notably, they are associated with local transmission networking, thus suggesting that this is the cause for the increased patterns of NNRTI resistance and not multiple transmissions of resistant strains from different sources among treated individuals. Our study highlights the advance of molecular epidemiology for understanding the dynamics of resistance. (Published: 2 November 2014) Citation: Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Paraskevis D et al. Journal of the International AIDS Society 2014, 17(Suppl 3): 19742 http://www.jiasociety.org/index.php/jias/article/view/19742 | http://dx.doi.org/10.7448/IAS.17.4.19742

Recombination is one of several factors that contribute to the great genetic diversity of human immunodeficiency virus type 1 (HIV-1). In the current study, analysis of the full-length genome of a novel complex mosaic HIV-1 isolate (99GR303) from a Greek sailor who was possibly infected in Sierra Leone, Africa is presented. The 99GR303 isolate was found to comprise genomic regions belonging to subtypes A, G, J and K as well as of regions of a subtype that remains unclassified. For a partial region of env as well as vpr, no apparent similarity to the known HIV-1 subtypes or to any of the circulating recombinant forms was found. In fact, in the partial env gene, including the C2-V3 region, the 99GR303 isolate formed a new clade, suggesting the existence of an additional HIV-1 subtype. Thus, novel recombinants embody partial genomic regions which may have originated either from subtypes that existed in the past and became extinct or from contemporary subtypes that are extremely rare.