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Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data.Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored.The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/μl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty.Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.

Q fever is a worldwide spread zoonotic disease, caused by the gram-negative intracellular bacillus Coxiella burnetii. Apart from its most common manifestations, Q fever has been reported to occasionally mimic autoimmune diseases. We herein present a case of acute Q fever in a 69-year-old man, manifesting as prolonged fever with pneumonitis, in whom biopsy of the temporal artery revealed giant cell arteritis. Moreover, PCR testing of the biopsy specimen was positive for Coxiella burnetii, thus further supporting the possibly infectious etiology of some cases of biopsy proven giant cell arteritis, with implications for treatment.

Our aim was to estimate vaccination and susceptibility rates against vaccine-preventable diseases among healthcare personnel (HCP) in eight hospitals.Cross-sectional survey.A total of 1284 HCP participated (physicians: 31.3%, nursing personnel: 36.6%, paramedical personnel: 11.1%, administrative personnel: 13.2%, supportive personnel: 7.3%). Vaccination rates were 32.9% against measles and mumps, 38.1% against rubella, 5.7% against varicella, 9.2% against hepatitis A, 65.8% against hepatitis B, 31.8% against tetanus-diphtheria, 7.1% against pertussis, 60.2% against influenza, and 80.1% against COVID-19. Susceptibility rates were as follows: 27.8% for measles, 39.6% for mumps, 33.4% for rubella, 22.2% for varicella, 86.3% for hepatitis A, 34.2% for hepatitis B, 68.2% for tetanus-diphtheria, and 92.9% for pertussis. Older HCP had higher susceptibility rates against mumps, rubella, varicella, hepatitis A, hepatitis B, tetanus-diphtheria, and pertussis (p-values0.001 for all). Mandatory vaccinations were supported by 81.85% of HCP.Although most HCPs supported mandatory vaccinations, significant vaccination gaps, and susceptibility rates were recorded. The proportion of susceptible HCP to measles, mumps, rubella, and varicella has increased in the past decade, mostly because of reduction in acquired cases of natural illness. Vaccination programs for HCP should be developed. A national registry to follow HCP's vaccination rates is urgently needed.

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.

Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19.Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death.IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations.IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment.gov, NCT04680949 and NCT04357366.

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.

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.

The Sanfilippo syndrome is an autosomal recessive mucopolysaccharidosis. Homocysteine and B12 status have not been described in this syndrome. A 21-year-old bedridden male with the Sanfilippo syndrome was hospitalized. He was in poor nutritional status according to laboratory and somatometric findings, he had an enlarged liver, moderate aortic valve insufficiency and was under antiepileptic, antipsychotic and anti-cholinergic therapy. The patient had moderate hyperhomocysteinemia (16.9 μmol/L) with co-existing high levels of serum B12 (1,765 pg/mL). In addition, cystathionine, methionine sulphoxide and certain amino acids were measured. It was hypothesized that a “functional” deficiency of vitamin B12 may be due to problematic transcobalamin-vitamin B12 complex dissociation. Moreover, the patient’s cardiovascular background and/or medical treatment may explain the observed hyperhomocysteinemia. B12 and homocysteine status should be assessed in Sanfilippo patients. This report suggests that checking vitamin B12 and homocysteine status may be useful in the Sanfilippo syndrome.

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.

ObjectiveImproving the quality of life (QoL) of people living with HIV (PLWH) has been proposed as a new priority in HIV care. The objective of this cross-sectional, qualitative study was to explore the perspectives of PLWH in Greece regarding their QoL.DesignTwenty-four semi-structured interviews were conducted with PLWH receiving care across six HIV clinics in Greece. The thematic analysis of the transcribed interviews resulted in four themes and eleven subthemes.ResultsFirst, fear of repercussions (e.g., stigmatization) makes PLWH reluctant to disclose their diagnosis in public settings or disclose accounting for factors like the confidant’s discretion. Second, participants are challenged by HIV’s unique biopsychosocial facets (e.g., uncertainty about symptoms) and fear for the future (e.g., a confidant revealing their HIV status without consent). Third, support received by specialist services is satisfactory in contrast to non-HIV specialist services, where significant improvements are needed to reduce stigmatization. Finally, the experiences of PLWH include contrasting elements of post-traumatic growth and an inability to accept their seropositivity (e.g., avoiding social interactions).ConclusionsEmpowering PLWH in these QoL areas is greatly needed. Increasing the life expectancy of PLWH is only the initial step; their QoL needs to be secured as the next priority in HIV care.

Σκοπός της παρούσας διατριβής είναι η μελέτη των μηχανισμών αντοχής πολυανθεκτικών στελεχών K.pneumoniae που απομονώθηκαν από ασθενείς της ΜΕΘ του Γενικού Νοσοκομείου Σερρών κατά τη διάρκεια της τετραετίας 2008-2011 και η αποτίμηση των μέτρων ελέγχου και ενεργού επιτήρησης που εφαρμόσθηκαν για την αναχαίτιση της διασποράς τους στο νοσοκομειακό περιβάλλον.Ο έλεγχος των στελεχών περιελάμβανε τον καθορισμό των MICs των κυριότερων αντιβιοτικών, φαινοτυπική δοκιμασία για την ανίχνευση παραγωγής καρβαπεμενασών καθώς και μοριακές μεθόδους τυποποίησης (PFGE). Για την ταυτοποίηση των γονιδίωντων β-λακταμασών (MBLs, KPCs, OXA – 48, AmpC, ESBLs) χρησιμοποιήθηκαν η μέθοδος PCR και η ανάλυση της νουκλεοτιδικής αλληλουχίας. Κατά τη χρονική διάρκεια της μελέτης απομονώθηκαν 49 στελέχη K. pneumoniae ανθεκτικά στην ιμιπενέμη και/ή την μεροπενέμη από κλινικά δείγματα 36 ασθενών της ΜΕΘ. Η πλέον συχνή εστία απομόνωσης ήταν τα ούρα (26,5 %) και ακολουθούσαν το αίμα (20,4%), οι βρογχικές εκκρίσεις (20,4%) και οι ενδοφλέβιοι καθετήρες (8,1%).Οι MICs της ιμιπενέμης κυμαίνονταν από 4 έως >32μg/ml, της μεροπενέμης από 2 έως > 32 μg/ml , ενώ όλα τα στελέχη παρουσίαζαν υψηλού βαθμού αντοχή στην ερταπενέμη με MICs > 32 μg/ml. Επιπλέον, όλα τα στελέχη ήταν ανθεκτικά στα β-λακταμικά αντιβιοτικά, συμπεριλαμβανομένων των συνδυασμών β-λακταμικών με αναστολείς των β-λακταμασών και της αζτρεονάμης, στην αμικασίνη, την τριμεθοπρίμη-σουλφαμεθοξαζόλη και τη σιπροφλοξασίνη.In vitro δραστικότητα έναντι των ανθεκτικών στις καρβαπενέμες στελεχών επέδειξαν η γενταμικίνη, η κολιστίνη και η τιγεκυκλίνη με 43 (87,7%) , 40 (83,6%) και 46 (94,5%) στελέχη να παραμένουν ευαίσθητα, αντιστοίχως.Ο φαινοτυπικός έλεγχος και η μοριακή τυποποίηση έδειξαν την παρουσία KPC και/ή καρβαπενεμάσης τύπου MBL σε όλα τα ανθεκτικά μικροβιακά στελέχη. Σε όλες τις περιπτώσεις, ο μοριακός έλεγχος με PCR επιβεβαίωσε τα αποτελέσματα των φαινοτυπικών δοκιμασιών.Ένα αντιπροσωπευτικό στέλεχος από κάθε ασθενή (συνολικά 36 στελέχη) μελετήθηκε περαιτέρω με PCR και ανάλυση νουκλεοτιδικής αλληλουχίας. Τα αποτελέσματα έδειξαν την παραγωγή KPC-2 από τα στελέχη που απομονώθηκαν από 24 ασθενείς, την παραγωγή VIM-1 από στελέχη 9 ασθενών και την συμπαραγωγή KPC-2 και VIM-1 από στελέχη 3 ασθενών. Ο φαινοτυπικός και ο μοριακός έλεγχος έδειξαν την συμπαραγωγή ESBL από 23 στελέχη που έφεραν το γονίδιο για KPC, από 6 στελέχη που έφεραν το γονίδιο για VIM και από 1 στέλεχος που παρήγαγε και τις δυο καρβαπενεμάσες. Πλασμιδικά γονίδια για AmpC δεν ανιχνεύθηκαν σε κανένα μικροβιακό στέλεχος. Η μοριακή τυποποίηση των αντιπροσωπευτικών στελεχών με PFGE έδειξε ότι ανήκαν σε διαφορετικούς κλώνους ( Ι-ΙΙΙ, ΙV- VI , VII και VIII ) ορισμένοι από τους οποίους διακρίνονταν σε υποτύπους.Κατά τη διάρκεια του δεύτερου έτους της μελέτης (2009) διαπιστώθηκε το ήμισυ περίπου των περιστατικών (16: 44,4%), ενώ 10 περιστατικά ανιχνεύθηκαν κατά τη διάρκεια του 4ου τριμήνου του έτους (Οκτώβριος –Δεκέμβριος) στο πλαίσιο επιδημίας. Αξίζει να σημειωθεί ότι τα δύο επόμενα έτη ο αριθμός των περιστατικών ελαττώθηκε σημαντικά (2010: 11 περ. 30,5%, 2011: 5 περ. 13,8%), ως αποτέλεσμα εφαρμογής ενός προγράμματος ελέγχου λοιμώξεων μετά το 2009. Η επίπτωση νέων περιστατικών ανά 1000 ασθενοημέρες ήταν 17,7 , 11,9 και 5,4 για το 2009 , 2010 και 2011, αντιστοίχως, με στατιστικά σημαντική μείωση να σημειώνεται κατά το τελευταίο έτος της μελέτης(p=0,0192).Κατά τη διάρκεια της επιδημίας του τελευταίου τριμήνου του 2009, αναπτύχθηκαν μόνο 3 ανθεκτικά στις καρβαπενέμες στελέχη από το περιβάλλον της ΜΕΘ. Δύο στελέχη προέρχονταν από συσκευές μηχανικής υποστήριξης της αναπνοής και 1 στέλεχος από νοσοκομειακή κλίνη. Σε 2 στελέχη ανιχνεύθηκαν KPC-2 ενώ το τρίτο στέλεχος παρήγε και τα δύο είδη καρβαπεμενασών. Η τυποποίηση με PFGE κατέδειξε ότι τα περιβαλλοντικά μικροβιακά στελέχη ανήκαν σε κλωνικούς υποτύπους, που είχαν ταυτοποιηθεί από κλινικά δείγματα.Κατά τη διάρκεια του 2011, στο πλαίσιο της ενεργού επιτήρησης, διαπιστώθηκε αποικισμός 11 ασθενών (11/97 ασθ. 11,3%), 24 ώρες μετά την εισαγωγή τους στη ΜΕΘ, με στελέχη K.pneumoniae ανθεκτικά στις καρβαπενέμες. Ο μοριακός έλεγχος έδειξε ότι όλα τα στελέχη παρήγαν το ένζυμο KPC-2 ενώ 8 παρήγαν συγχρόνως και μια ESBL. Τα στελέχη ανήκαν σε κλωνικούς υποτύπους, που είχαν ανιχνευθεί σε κλινικά δείγματα.Ελήφθησαν μέτρα απομόνωσης των αποικισθέντων ασθενών ενώ 3/11 ανέπτυξαν λοίμωξη από ανθεκτικό στέλεχος K.pneumoniae, 4-16 ημέρες μετά τον έλεγχο αποικισμού.Τα ευρήματα της μελέτης υποδηλώνουν ότι η εφαρμογή αυστηρών μέτρων πρόληψης και ενεργού επιτήρησης των λοιμώξεων μπορούν να ελαττώσουν την επίπτωση της δευτερογενούς μετάδοσης παθογόνων που παράγουν KPC στο χώρο της ΜΕΘ.

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)

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Background Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Methods Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/μL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/μL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Results Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. Conclusions PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. Clinical Trials Registration NCT03041051.

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.

Antiretroviral therapy (ΑRT) has successfully decreased AIDS morbidity and mortality and increased the lifespan of HIV patients to several decades. However, numerous factors contribute with unknown mechanisms to chronic immune activation and inflammation leading to severe “non-AIDS morbidities’’. Platelet Activating Factor (PAF) is a potent lipid inflammatory mediator with important role in the ‘’non-AIDS morbidities’’. The purpose of this study was to investigate whether tenofovir-DF/emtricitabine and abacavir/lamivudine with atazanavir boosted ritonavir (ART_A and ART_B, respectively) affect in vitro PAF activity and in vivo PAF levels and metabolism. In this intent, the two ART regimens were examined in vitro against platelet aggregation induced by PAF. In addition, PAF levels and PAF metabolic enzymes were determined in HIV-1 infected volunteers before and after the initiation of antiretroviral therapy for a 12-month period. The in vitro results showed that ritonavir was the most potent inhibitor against PAF induced platelet aggregation while abacavir presented the less potent action. The in vivo results showed that tenofovir-DF/emtricitabine with atazanavir-r seems not to affect PAF levels and metabolism while abacavir/lamivudine with atazanavir-r increased bound and total PAF blood levels, PAF biosynthesis in platelets and also decreased Lp-PLA2 activity. In addition, ART_B revealed higher lyso-PAF-AT specific activity at 3rd, 6th and 9th month (p3=0.04, p6=0.04 and p9=0.03) compared to ART_A. In conclusion, there is a direct relation between in vitro and in vivo effect of antiretrovirals on PAF and abacavircontaining regimen activates PAF biosynthesis leading to elevated PAF levels.

To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART.SMART patients from sites that determined platelets routinely.Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2.Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/μl (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P0.0001)] and the rate of developing thrombocytopenia (100 000/μl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels.Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.

Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein-associated-phospholipase-A(2) (LpPLA(2)) in plasma, were measured in blood samples of eight asymptomatic naive male HIV-infected patients just before and after 1, 3, and 6 months of treatment. CD4 cell counts, viral load, and several biochemical markers were also measured in the same blood samples of these patients. The repeated measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations-partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA(2) in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF-biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA(2) remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir-DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated.

Platelet-activating factor (PAF), a mediator of proatherosclerotic inflammatory processes, is also implicated in endothelial dysfunction during human immunodeficiency virus (HIV) infection. We examined PAF metabolism in blood of naive male patients, 8 with early HIV infection (group A) and 17 just before treatment initiation (group B), versus 18 healthy age-matched males (group C). Statistical analysis was performed with 1-way analysis of variance (ANOVA) criterion and Pearson r test. Higher PAF biosynthesis in patients’ leukocytes versus group C was accompanied by an increase in lipoprotein-associated phospholipase A2 (Lp-PLA2) activity that degrades PAF. Moreover, PAF synthesis was higher and Lp-PLA2 activity was lower in group B compared to group A. Lipoprotein-associated phospholipase A2 was positively correlated with viral load and negatively correlated with CD4 cell counts in group B. The activities of PAF-basic biosynthetic enzymes in patients’ leukocytes were also negatively correlated with CD4 cell counts. The observed continuous increase in PAF biosynthesis during HIV infection progress seems to amplify the risk of AIDS manifestations and/or cardiovascular complications in HIV-infected patients, while a subsequent increase in Lp-PLA2 activity seems to be a host response.

Ginkgo biloba products seem to protect from several pathological conditions, including HIV manifestations, where Platelet Activating Factor (PAF) is implicated. In the present study, we examined for the first time the in vivo effects of a standardized formulation of Ginkgo biloba extract (150 mg daily, per os) on PAF metabolism in blood cells and plasma of two male, asymptomatic HIV-infected patients, not receiving antiretroviral treatment, during a 9-month period. These patients differed at baseline in terms of duration of HIV infection, viral load levels, CD4 cell counts and Highly Active Antiretroviral Therapy (HAART) experience. In the first patient with early HIV infection, after an initial transient increase, a return of both plasma viral load and PAF biosynthetic enzyme activities in leukocytes to their baseline levels was observed during Ginkgo biloba use. As a result PAF degradation also remained low in this patient. The second patient with late but not advanced HIV infection, had higher levels of viral load and a lower CD4 cell count at baseline. The use of 150 mg of a Ginkgo biloba extract was probably insufficient to induce PAF degradation and/or to suppress the induction of PAF biosynthesis observed. At the same time, the initial high levels of viral load were further increased and CD4 cell counts were finally decreased during the study. The observed differences in PAF metabolism during Ginkgo use seem to be related to the initial heterogeneity of these patients. It appears that in some HIV-infected patients inhibition of the PAF/PAF-receptor system, along with a decrease/down-regulation of PAF-biosynthesis, illustrates a new potential role for Ginkgo biloba compounds in the treatment of HIV infection and its manifestations. However, more tests on a larger number of patients are needed in order to support these preliminary observations.

Doppler tissue imaging (DTI) is a useful tool for the detection of subtle systolic function abnormalities related to the longitudinal contraction. We assessed left ventricular (LV) systolic function with DTI in 45 human immunodeficiency virus (HIV)-infected patients without any heart-related symptoms and in 30 healthy control subjects. Although conventional echocardiography showed no differences between groups, DTI revealed lower peak systolic velocities in group A patients when compared with group B ones (Sms: 8.84 ± 0.94 cm/s vs. 9.42 ± 0.84 cm/s, respectively, P < 0.001 and Sml: 9.58 ± 1.86 cm/s vs. 10.78 ± 2.07 cm/s P = 0.003). In group A patients, both peak systolic myocardial velocities at the septal (Sms) and lateral mitral annulus (Sml) correlated with CD4 lymphocyte count (P = 0.034 and 0.009, respectively). We conclude that pulse wave DTI reveals subtle and non-otherwise detectable abnormalities of the longitudinal LV contractile function in asymptomatic patients with positive HIV serology. DTI study should potentially be expanded in the population of HIV-infected patients, aiming at an early identification of LV systolic dysfunction.

Combined antiretroviral treatment (cART) modifications are often required due to treatment failure or side effects. We investigate cART regimens' durability, frequency of treatment-limiting adverse events, and potential risk factors and temporal trends. Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). Statistical analyses were based on survival techniques, allowing for multiple contributions per individual. Overall, 2,756 individuals, aged15 years, initiated cART. cART regimens were grouped by their initiation date into four calendar periods (1995-1998, 1999-2002, 2003-2006, and 2007+). Median [95% confidence interval (CI)] time to first treatment modification was 2.11 (1.95-2.33) years; cumulative probabilities at 1 year were 31.6%, 29.0%, 33.1%, and 29.6% for the four periods, respectively. cART modifications were less frequent in more recent years (adjusted HR=0.96 per year; p0.001). Longer treatment duration was associated with lower HIV-RNA, higher CD4 counts, and being previously ART naive. cART modifications due to treatment failure became less frequent in recent years (adjusted HR=0.91 per year; p0.001). Estimated (95% CI) 1 year cumulative probabilities of treatment-limiting side effects were 16.4% (12.0-21.3%), 19.3% (15.6-23.3%), 24.9% (20.3-29.7%), and 21.1% (13.4-29.9%) for the four periods, respectively, with no significant temporal trends. Risk of side effects was lower in nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens or triple nucleoside reverse transcriptase inhibitor (NRTI)-based cART regimens. Treatment modifications have become less frequent in more recent years. This could be partly attributed to the lower risk for side effects of NNRTI-based cART regimens and mainly to the improved efficacy of newer drugs. However, the rate of drugs substitutions due to adverse events remains substantially high.

The prevalence of HIV-1 drug resistance mutations in naïve patients has been previously shown to differ greatly with the geographic origin. The purpose of this study was to prospectively estimate the prevalence of HIV-1 drug resistance in Greece by analyzing a representative sample of newly HIV-1 diagnosed patients, as part of the SPREAD collaborative study. Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 101 newly diagnosed HIV-1 patients, in Greece, during the period September 2002--August 2003, representing one-third of the total newly diagnosed HIV-1 patients in the same time period. The prevalence of HIV-1 drug resistance was estimated according to the IAS-USA mutation table taking into account all mutations in RT and only major mutations in PR region. The overall prevalence of resistance was 9% [95% confidence interval (CI): 4.2--16.2%]. The prevalence of mutations associated with resistance to NRTIs was 5% (95% CI: 1.6--11.2%), for NNRTIs was 4% (95% CI: 1.1--9.8%), while no major resistance mutations were found in PR. No multi-class resistance was detected in the study population. The prevalence of resistant mutations in the recent seroconverters was 22%. For two individuals, there was clear evidence for transmitted resistance based on epidemiological information for a known source of HIV-1 transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%.

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

Objective: To evaluate the long-term effects of different boosted protease inhibitors (bPIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral regimens on lipid levels in HIV seropositive individuals who have not received lipid-lowering agents. Methods: Data consisted of 595 patients participating in the population-based Athens Multicenter Cohort Study who were consistently followed up during 1996–2008. Results: In naive patients, lipid parameters increased sharply during the first 3 months of antiretroviral therapy and reached a plateau level approximately 6–9 months after therapy initiation. The plateau levels remained almost stable for up to 3·5 years. In general, bPIs exerted a more pronounced effect compared to NNRTIs. Conclusions: The administration of PI- or NNRTI-based regimens especially in naive but also in unboosted PI experienced patients provoked a sharp increase in lipid levels that remained stable in higher levels for more than 3 years.

Human Immunodeficiency Virus (HIV)-infected patients are at increased risk for cardiovascular diseases partly due to chronic inflammation. Some antiretroviral drugs and Highly Active Anti-Retroviral Therapy (HAART) regimens seem to be related and amplify this increased risk, especially the ones containing abacavir. Platelet-Activating-Factor (PAF) is a potent inflammatory mediator that is implicated in both cardiovascular diseases and HIV-related manifestations. Our objective is to study the in vivo effect of the abacavir/lamivudine/efavirenz first-line HAART regimen on PAF metabolism in HIV-infected patients. The specific activities of PAF basic biosynthetic enzymes in leukocytes and platelets, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT), but also those of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets and Lipoprotein-associated-Phospholipase-A2(LpPLA2) in plasma, were measured in blood samples of 10 asymptomatic naïve male HIV-infected patients just before and after 1, 3 and 6 months of treatment. CD4 cell counts, viral load and several biochemical markers were also measured in the same blood samples of these patients. The repeated ANOVA measures and the Pearson r criterion were used for studying statistical differences and correlations - partial correlations respectively. Even though viral load was decreased and CD4 cell counts were beneficially increased after treatment with the abacavir/lamivudine/efavirenz regimen, the main enzyme of the remodelling PAF-synthesis that is implicated in pro-atherogenic inflammatory procedures, Lyso-PAF-AT activity, was increased at 3 months of treatment in both leukocytes and platelets, while the main enzyme of PAF-degradation, PAF-AH, was increased as a response only in leukocytes at the 3rdmonth. Although the abacavir/lamivudine/efavirenz HAART regimen exhibits very efficient antiretroviral activities, on the other hand it induces an in vivo transient increase in the inflammation-related remodeling PAF-biosynthetic pathway. This finding supports the hypothesis of inflammation-mediated increased cardiovascular risk in HIV-infected patients during the first months of abacavir-containing HAART.

Platelet-activating factor (PAF) is a potent inflammatory mediator, which seems to play a role in the pathogenesis of several AIDS manifestations such as AIDS dementia complex, Kaposi's sarcoma, and HIV-related nephropathy. PAF antagonists have been studied in these conditions with promising results. In order to examine the possible interactions between PAF and antiretroviral therapy, we studied the effect of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors against PAF biological activities and its basic biosynthetic enzymes dithiothreitol-insensitive PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT), as well as its main degradative enzyme PAF-acetylhydrolase, of human mesangial cell line (HMC). We also studied the effect of several backbones and highly active antiretroviral therapy (HAART) regimens against PAF activity. Among the drugs tested, several inhibited PAF-induced platelet aggregation in a concentration-depended manner, with tenofovir, efavirenz, and ritonavir exhibiting the higher inhibitory effect. In addition, when these drugs were combined in backbones and HAART regimens based on American antiretroviral therapy proposals, they also synergistically exhibited an inhibitory effect against PAF-induced platelet aggregation. Several of these drugs have also inhibited in vitro microsomal PAF-CPT activity, and concentrations of lopinavir-r or tenofovir-DF (similar to their IC(50) against PAF-induced platelet aggregation) exhibited the same effect against PAF-CPT and Lyso-PAF-AT when added in the cell medium of cultured HMC. In addition, in naïve patients treated with one of the most potent anti-PAF HAART regimens (efavirenz/emtricitabine/tenofovir-DF) for a period of 1 month, a significant reduction of the specific activity of PAF-CPT of washed human leukocytes of these patients was also observed, compared with its levels before the HAART treatment. These promising results need to be further studied and confirmed by additional in vivo tests in order to optimize HAART efficacy.

The Procleix Ultrio human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus (HCV)/hepatitis B virus (HBV) (Ultrio) assay simultaneously detects HIV-1 RNA, HCV RNA and HBV DNA in individual blood donations. The main objective of the study was to assess the analytical and clinical sensitivity of the multiplex and discriminatory probe assays in samples with a low viral load.The VQC HIV RNA genotype B, HCV RNA genotype 1 and HBV DNA genotype A standard dilutions were tested in 26 repeats. The probability of detection by Ultrio was compared with previously obtained data of the Procleix Duplex HIV-1/HCV assay on the same reference panels. A selection of 121 anti-HIV-1, 138 anti-HCV and 190 HBsAg positive samples from patients receiving antiviral therapy were tested. The majority of patient samples had a viral load below the detection limit of the diagnostic nucleic acid test assays, which made them suitable to evaluate the performance of the multiplex and discriminatory assays on yield cases with a similar low viral load.The 95% and 50% detection end-points of the Ultrio assay along with the corresponding 95% confidence intervals are 53.7 (32.9-117.2) and 8.6 (6.2-12.1) geq/ml for HIV-1 RNA, 30.3 (19.0-62.4) and 5.2 (3.7-7.2) geq/ml for HCV RNA and 393.7 (147.9-6978) and 54.5 (22.4-143.8) geq/ml for HBV DNA. The analytical sensitivity of Ultrio expressed as a potency factor relative to previously obtained Duplex results on the same HIV-1 RNA and HCV-RNA standard dilutions was 1.09 (0.20-6.10) and 1.11 (0.21-5.89), respectively. The assay detected all 22 HIV-1 infected patients with viral load50 copies/ml, and 41 of 99 patients (41%) with viral load50 copies/ml, of which 23 (56%) were detected by the discriminatory assay. All 47 patients with HCV RNA load521 IU/ml and 10/91 polymerase chain reaction-negative patients with viral load50 IU/ml tested positive in Ultrio assay of which five were missed in the discriminatory test. The assay detected 53/55 HBV infected patients (96%) with viral load250 copies/ml and 108/135 patients (80%) with viral load250 copies/ml of which 17 (16%) were missed by the discriminatory test.The new Procleix Ultrio assay is as sensitive as the Procleix Duplex assay for HIV-1 and HCV detection meeting the requirements of universal guidelines. The ability of the assay to detect HBV DNA in low viral load samples could be useful for screening blood. Inevitable negative results of discriminatory probe assays caused by stochastic sample variation will reduce the chance of recognizing low viraemic blood donors detected by individual donation nucleic acid test.

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

Purpose of the study PAF, a potent inflammatory mediator, seems to play a role in the pathogenesis of several AIDS manifestations. PAFantagonists have been studied in this context with promising results. We have previously described the in vitro interaction between HAART and PAF-induced platelet aggregation, as well as between HAART and the specific activities of the basic PAF metabolic enzymes.