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(1) Background: Access to laboratory testing services for HIV in Greece is persistently challenged and this impacts both the continuum of care and, potentially, equity in access. (2) Methods: A cross-sectional study with two parts (first part: HIV-positive people/PLWHIV; second part: HIV clinicians) was conducted in Greece to quantify challenges regarding access to laboratory testing for HIV. Data were collected through online surveys, during a one-month period, between 2019 and 2020. The total sample consisted of 153 PLWHIV and 26 HIV clinicians. (3) Results: Access to viral load testing varied significantly according to place of residence (p = 0.029) and year of diagnosis (p = 0.054). Patients diagnosed after 2015 reported worse access to viral load testing (72.7% vs. 85.9%). Over one third of respondents perceived viral load tests as being not at all accessible (11.4%) or somewhat accessible, only after facing multiple systemic obstacles (24.2%). Equally, most of HIV clinicians reported barriers or no access to baseline viral load testing (80%) and baseline genotype resistance tests (96%). (4) Conclusions: Access of people diagnosed with HIV to CD4 lymphocyte tests and genotype resistance screening is significantly challenged in Greece, especially after 2015. Addressing this challenge is critical in removing access barriers and achieving the UNAIDS 95-95-95 HIV elimination goals.

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.

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.

Objective Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. Methods Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2, Graphical abstract Image 1

In light of the accumulating evidence for survival benefit coming from the use of macrolides for community-acquired pneumonia (CAP), a group of experts from the field of internal medicine and infectious diseases frame a position statement on the use of macrolides for the management of bacterial CAP and for infection by the novel coronavirus (COVID-19). The statement is framed taking into consideration existing publications and own research experience. The main content of this statement is that the combination of one β-lactam and a macrolide should be the first treatment of choice for patients with severe bacterial CAP. Severity is assessed as scoring 2 or more points on the CURB65 scoring system of severity or as pneumonia severity index III to V or C-reactive protein more than 150 mg/l; the suggested macrolide is either azithromycin or clarithromycin. The experts also suggest that in COVID-19 pneumonia, the combination of one β-lactam and a macrolide should be reserved only when there is strong suspicion of bacterial co-infection.

Background To investigate intention rates to get vaccinated against COVID-19 among healthcare personnel (HCP) in Greece. Methods Cross-sectional survey. Results The response rate was 14.5%. Of 1521 HCP with a known profession, 607 (39.9%) were nursing personnel, 480 (31.6%) physicians, 171 (11.2%) paramedical personnel, 72 (4.7%) supportive personnel, and 191 (12.6%) administrative personnel. Overall, 803 of 1571 HCP (51.1%) stated their intention to get vaccinated while 768 (48.9%) stated their intention to decline vaccination. Most HCP (71.3%) who reported intent to get vaccinated noted contributing to the control of the pandemic and protecting their families and themselves as their reasons, while the most common reason for reporting intent to decline vaccination was inadequate information about the vaccines (74.9%), followed by concerns about vaccine safety (36.2%). Logistic regression analysis revealed that the probability of intending to get vaccinated increased with male gender, being a physician, history of complete vaccination against hepatitis B, history of vaccination against pandemic A (H1N1) in 2009–2010, belief that COVID-19 vaccination should be mandatory for HCP, and increased confidence in vaccines in general during the COVID-19 pandemic. The following factors were associated with a lower intention to get vaccinated: no vaccination against influenza the past season, no intention to get vaccinated against influenza in 2020–2021, and no intention to recommend COVID-19 vaccination to high-risk patients. Conclusion There is an urgent need to built safety perception towards COVID-19 vaccines and raise vaccine uptake rates by HCP, and thus to protect the healthcare workforce and the healthcare services.

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 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.

Although the connection of [secondary hemophagocytic syndrome (sHS)] with HIV has been well documented, optimal treatment regimen is not well established. This is due not only to the rarity of the syndrome, but also to the heterogeneity of the involved population. Most cases are related to opportunistic infections or malignancies in advanced stage, but many cases are also related to seroconversion, in the primary infection setting. Moreover, in the [antiretroviral treatment (ART)] era, rare cases of ART-related sHS have been reported. In these, often fatal cases, an [immune reconstitution inflammatory syndrome (IRIS)] process is involved, posing a serious challenge to the treating physician. We hereby report a case of successful treatment of an HIV patient with primary effusion lymphoma who experienced sHS shortly after ART onset. Our patient, treated with high dose dexamethasone and gamma globulin, achieved complete remission. This case might hint possible therapeutic insights in the treatment of IRIS-related sHS.

Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA500 copies/ml) and time to failure (500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

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.

Background: Calcific myonecrosis is a rare late complication of trauma, affecting almost exclusively the lower limb. Its radiologic appearance is characteristic. Superimposed infection usually is a sequela of biopsy. Case Report: We present three patients, one with bilateral involvement, who presented with calcific myonecrosis and spontaneous infection. Three infections were attributable to a single microorganism: Enterobacter cloacae, Staphylococcus hominis, and S. haemolyticus were recovered. Multiple microorganisms were responsible in the other case. Treatment consisted of radical surgical debridement and antibiotics. The incision was closed over a suction drain, where possible, or left open to close by secondary intention. Conclusions: Calcific myonecrosis may present as infection without any obvious precipitating factor, and it should be included in the differential diagnosis in cases of soft tissue infection of the leg.

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.

The COBAS TaqMan HIV-1 test (Roche Diagnostics) was compared with the LCx HIV RNA quantitative assay (Abbott Laboratories), the Versant HIV-1 RNA 3.0 (bDNA) assay (Bayer) and the COBAS Amplicor HIV-1 Monitor v1.5 test (Roche Diagnostics), using plasma samples of various viral load levels from HIV-1-infected individuals. In the comparison of TaqMan with LCx, TaqMan identified as positive 77.5% of the 240 samples versus 72.1% identified by LCx assay, while their overall agreement was 94.6% and the quantitative results of samples that were positive by both methods were strongly correlated (r=0.91). Similarly, in the comparison of TaqMan with bDNA 3.0, both methods identified 76.3% of the 177 samples as positive, while their overall agreement was 95.5% and the quantitative results of samples that were positive by both methods were strongly correlated (r=0.95). Finally, in the comparison of TaqMan with Monitor v1.5, TaqMan identified 79.5% of the 156 samples as positive versus 80.1% identified by Monitor v1.5, while their overall agreement was 95.5% and the quantitative results of samples that were positive by both methods were strongly correlated (r=0.96). In conclusion, the new COBAS TaqMan HIV-1 test showed excellent agreement with other widely used commercially available tests for the quantitation of HIV-1 viral load.

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%.

The LCx HIV RNA quantitative assay (Abbott Laboratories, Delkenheim, Germany) was compared with the Versant HIV-1 RNA 3.0 (bDNA) assay (Bayer, Tarrytown, NY) and the COBAS Amplicor HIV-1 Monitor v1.5 test (Roche Diagnostics, Branchburg, NJ), using plasma samples of various viral load levels from HIV-1-infected patients. Considering the lower limit of the linear range of 50 copies/ml of both assays, the detection range of the LCx was 127/151 (84.1%) versus the 131/151 (86.8%) of the bDNA 3.0 assay, while overall agreement between the two assays was 93.4% (141/151). LCx and bDNA 3.0 results were found to be strongly correlated ( r = 0.96). The fitted regression line was described by the equation log 10 (LCx copies/ml) = 0.05 + 1.06 × log 10 (bDNA 3.0 copies/ml) with 95% CI for the estimated slope and intercept at 1.01, 1.12 and −0.16, 0.26, respectively. Similarly, the detection range of the LCx was 115/148 (77.7%) versus the 128/148 (86.5%) of the Monitor v1.5 test. A 91.2% concordance (135/148) was observed between these two assays at a cut-off of 50 copies/ml. LCx and Monitor v1.5 results were highly correlated ( r = 0.96). The fitted regression line was described by the equation log 10 (LCx copies/ml)=0.06 + 1.03 × log 10 (Monitor v1.5 copies/ml) with 95% CI for the estimated slope and intercept at 0.97, 1.09 and −0.16, 0.28, respectively.

TMA = transcription-mediated amplification.From the Department of Hygiene and Epidemiology, Athens University Medical School, Athens; the Second Regional Blood Transfusion and Comprehensive Haemophilia Care Center, Laiko General Hospital, Athens; the Red Cross General Hospital, Athens; the First Department of Internal Medicine, Western Attica General Hospital, Athens; and the Department of Nephrology, Laiko General Hospital, Athens, Greece.

The widespread use of antiviral drugs against HIV has increased the prevalence of HIV-1 resistant strains among naïve individuals due to transmission of resistant strains. The purpose of this study was to investigate the presence of HIV-1 strains harboring resistance mutations in naïve patients in Greece. Blood samples were collected from 25 individuals. The DNA sequence of protease and partial reverse transcriptase regions (codons 41-223) were obtained by direct sequencing. Our results showed the absence of any primary resistance mutations in the study population. However, we were able to identify high prevalence of sequence polymorphisms at positions in reverse transcriptase region associated mainly with resistance to NNRTIs. Moreover, in protease region several secondary mutations were detected, suggesting the higher genetic variability of this region. The clinical significance of the polymorphisms associated with reduced susceptibility to NNRTIs remains to be clarified.

To evaluate the safety and antiviral action of interferon-alpha (IFN-alpha) in HIV-1 infection, we undertook a proof of concept study in 27 treatment-naive patients. Eligible patients comprised two groups: the IFN-alphaT group (n = 17), which received 5 MIU IFN-alpha s.c. daily for 32 consecutive days, and the IFN-alphaNT group (n = 10), which did not receive IFN-alpha prior to highly active antiretroviral therapy (HAART), which was commenced on day 28 in both groups. IFN-alphaTreatment was well tolerated in 14 of the 17 patients of the IFN-alphaT group who completed the study. The mean HIV RNA reduction in the IFN-alphaT group on day 14 was 1.1 log(10). Viral load suppression was inversely associated with baseline viral load (p = 0.031). Four weeks after initiation of HAART, IFN-alphaT and IFN-alphaNT group patients had 2.40 and 1.82 log(10) HIV RNA reduction from baseline, respectively (p0.001). There was no evidence of cross-resistance with existing antiretrovirals in patients with HIV-RNA rebound after initial plasma viral load declineor = 1 log(10) during IFN-alpha monotherapy. Thus, low daily IFN-alpha exhibits potent anti-HIV-1 activity in vivo without serious adverse effects. These properties render IFN-alpha an attractive candidate for further assessment as a constituent of HAART.

To determine virological and immunological response to highly active antiretroviral therapy (HAART) and to investigate factors influencing response in a community-based setting.Plasma HIV RNA levels and CD4 cell counts were studied in 168 unselected individuals starting HAART including indinavir or ritonavir or hard-gel saquinavir-containing regimens.Overall, 60% of the patients reduced their HIV RNA to below 500 Eq/mL, but half of them experienced a subsequent virologic rebound. Patients with higher baseline HIV RNA, higher baseline CD4 cell count, and simultaneous initiation of combination therapy and patients on indinavir or ritonavir regimen were more likely to have virologic response within 6 months since HAART initiation. Patients with lower baseline CD4 cell count and with lower rates of viral clearance had a higher probability of a subsequent virologic rebound. Forty percent of the patients had increased their CD4 cell counts by more than 100 cells/microL (immunologic response). The probability of immunologic response was independent of baseline HIV RNA levels and CD4 cell count; however, the more complete the virologic suppression, the higher the probability of immunologic response. Thirty percent of the patients had discordance between virologic and immunologic responses.The rate of virologic failure in this unselected group of patients was higher than that observed in randomized clinical trials, but only a minority (11%) of the patients were treatment naïve. Starting combination therapy simultaneously and initiating antiretroviral therapy before advanced HIV disease has developed predict virologic response, whereas the magnitude of viral suppression predicts mid to long immunological response.

We present the rare case of a 64-year-old man who developed knee pyarthrosis due to Nocardia asteroides following intraarticular injections. The patient was suffering from chronic lymphocytic leukaemia; however, there were no signs of disseminated Nocardia infection. The patient was treated with antibiotics, arthroscopic lavage of the joint and paracentesis of a cyst that was formed in the popliteal fossa and calf.

The HIV-1 subtype distribution in 83 HIV-1-seropositive individuals living in Greece was investigated by using the heteroduplex mobility assay (HMA), DNA sequencing, and phylogenetic analysis. The results revealed that partial HIV-1 gp120 sequences from 71 (86%) patients were subtype B, 5 (6%) were subtype A, 4 were subtype D (5%), 2 (2%) were subtype C, and 1 (1%) was subtype I. The subtype I isolate was documented in an intravenous drug user. A high prevalence (90-100%) of B isolates among intravenous drug users, hemophiliacs, and homosexual men was observed, in contrast to heterosexuals, among whom non-B subtypes seemed to be common (42.9%, p < 0.001). Among the Greek population subtype B is the most frequent (94%), in contrast to the high prevalence (57%) of non-B isolates found in emigrants living in Greece (p < 0.001). A heterosexual transmission case of subtype D in a Greek individual not traveling abroad was also documented. The broad HIV-1 diversity in Greece may be explained by population movements, such as migration and traveling.

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

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.

To assess the attitudes about mandatory vaccination and vaccination coverage against vaccine-preventable diseases among health-care workers (HCWs) working in tertiary-care hospitals in Greece.A questionnaire was distributed to HCWs working in four tertiary-care hospitals.In total, 505 HCWs participated in the survey. Self-reported completed vaccination rates were 18.8% against measles, 18.8% against mumps, 22.2% against rubella, 1.9% against varicella, 3.6% against hepatitis A, 56.5% against hepatitis B, and 35.7% against tetanus-diphtheria. Younger age groups had higher completed vaccination rates against measles, mumps, rubella, varicella, and hepatitis B compared with older HCWs (p-value 0.001). Self-reported susceptibility rates were 12.7% for measles, 18.9% for mumps, 15.8% for rubella, 15.2% for varicella, 89.9% for hepatitis A, 34.2% for hepatitis B, and 64.3% for tetanus-diphtheria. Sixty three percent of 451 HCWs who answered this question supported mandatory vaccinations for HCWs, with significant differences per target disease. Physicians more frequently supported a mandatory vaccination policy compared to nurses and other professions (72.1% versus 61.9% and 54.2%, respectively; p-value = 0.028).Approximately two thirds of HCWs working in tertiary-care hospitals in Greece support mandatory vaccinations for HCWs, however suboptimal vaccination rates against vaccine-preventable diseases were recorded.

A significant increase (more than 10-fold) in the number of newly diagnosed HIV-1 infections among injecting drug users (IDUs) was observed in Greece during the first seven months of 2011. Molecular epidemiology results revealed that a large proportion (96%) of HIV-1 sequences from IDUs sampled in 2011 fall within phylogenetic clusters suggesting high levels of transmission networking. Cases originated from diverse places outside Greece supporting the potential role of immigrant IDUs in the initiation of this outbreak.

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.

Objective: Prolonged intestinal replication of polioviruses has not previously been studied in Greek AIDS patients. The objective of our study was to estimate the prevalence of enteroviral infections in this population. Methods: Nineteen stool samples were investigated from 19 different patients. Collection took place at the Hellenic Red Cross Hospital, Athens, Greece, between August and October 2002. Samples were processed as follows: virus isolation was attempted by cell culture using three different cell lines (human epidermoid carcinoma [Hep]-2, rabdomyosarcoma [RD], and mouse cells genetically modified in order to express the polio virus receptor in their cell surface [L20b]). An enterovirus-specific reverse transcription (RT)-PCR was then applied. Finally, seroneutralization tests were performed on 11 blood samples taken from a number of the patients who had supplied stool samples. Results: Samples were negative for enterovirus detection of any serotype on all cell lines. No cytopathic effect was observed. Enterovirus-specific RT-PCR assays were also negative for the detection of enteroviral RNA. Seroneutralization revealed relatively high antibody titers against poliovirus 1 and 2 in three of the eleven blood samples. Conclusions: Greek AIDS patients are not vulnerable to enteroviral infections and do not constitute a potential reservoir of poliovirus-prolonged excretion in Greece.

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

HIV-1 RNA measurements from 84 plasma specimens obtained with the QUANTIPLEX HIV-1 RNA 2.0 and 3.0 (bDNA) assays (Chiron Diagnostics, Emeryville, CA) and with the AMPLICOR HIV-1 MONITOR™ Test, version 1.5 with ultra-sensitive specimen preparation (Roche Diagnostic Systems, Inc., Branchburg, NJ) were compared. The absolute RNA values of tested specimens differed significantly between bDNA 2.0 and bDNA 3.0 or Monitor v1.5 measurements (Wilcoxon signed-rank test P

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.

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.

Inclusion of darunavir and etravirine significantly increased the percentage of patients having at least one fully-active drug from two or three different drug categories. Specifically, this percentage changed from 21% to 44% (two categories) and from 15% to 31% (three categories) (p < 0.001). Interestingly, in the study population, 81 (58%) individuals had no options in the N(t)RTI class. Concerning the other drug classes, 33 (41%) individuals had no available NNRTIs, while 58 (72%) of them had less than two options among the PIs.

Background Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. Methods We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively. Results Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentration-depended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity. Conclusions These newly found properties of antibiotics used in sepsis suggest that apart from their general actions, these drugs may present additional beneficial anti-inflammatory and anti-coagulant effects against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor and/or the thrombin/protease-activated-receptor-1 systems, and/or by reducing PAF-levels through both PAF-biosynthesis inhibition and PAF-catabolism induction. These promising in vitro results need to be further studied and confirmed by in vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis.