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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.

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.

Objective: HIV infection is currently regarded as a global chronic disease. The purpose of this study was to assess the direct cost of illness per patient per year in Greece. Methods: A retrospective study for the estimation of the direct cost of HIV infection was performed from the third-party payer perspective. Data from 447 patients monitored in a general hospital of Athens were collected from their medical records. The survey involved all services and treatments that patients (stratified into three health states according to the number of CD4 cells/ml as defined by the Centers for Disease Control and Prevention classification system for HIV infection) received in 1 year, as well as demographic data. Results: The annual direct cost per patient was calculated at €6859 €4699. Antiretroviral therapy cost was estimated at €5741, while the annual cost of providing health care services regardless of health state was computed at €1118, with laboratory investigation and imaging studies representing €924 (13.5%), outpatient visits €34 (0.5%), and hospitalization €160 (2.3%) of total cost, respectively. Overall, direct cost per patient was found to increase as the CD4 T lymphocytes decreased, leading to prolonged hospitalization and an increase in the number of laboratory tests. Direct cost for patients with more than 500 CD4 cells/μl was estimated at €6067, whereas for those with 200 to 499 cells/μ la nd less than 200 cells/μl, it was assessed at €6857 and €7654, respectively. Conclusions: The direct cost of HIV infection per patient increased as CD4 T lymphocytes decreased. The largest part of expenses was attributed to antiretroviral therapy, followed by laboratory tests/imaging studies, hospitalization, and finally outpatient visits.

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.

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.

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.

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.

Background: Persistent immune activation and inflammation are lying behind HIV-infection even in the setting of ART mediated viral suppression. The purpose of this study is to define the in vivo effect of two first-line ART regimens on certain inflammatory mediators in male HIV patients. Methods: Male, naive, HIV-infected volunteers were assigned either to tenofovir-DF/emtricitabine/efavirenz (Group_T) or abacavir/lamivudine/efavirenz (Group_A). Platelet Activating Factor (PAF) levels and metabolic enzymes together with HIV-implicated cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFa) and VEGF were determined for a 12-month period. Differences within each group were determined by non-parametric Friedman and Wilcoxon test, while the differences between the groups were checked by ANOVA repeated measures. Results: Both ART regimens present pronounced effect on inflammatory mediators, resulting in decreased PAF levels and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity for tenofovir-containing regimen and same as baseline PAF levels with a peak though at the 3 rd month as well as elevated Lp-PLA2 activity for abacavir-containing regimen. Conclusions: Studies regarding the effect of first-line ART regimens on inflammation may be beneficial in preventing chronic morbidities during HIV-treatment. From this point of view, the present study suggests an anti-inflammatory effect of tenofovir-containing ART, while the temporary increase of PAF levels in abacavir-containing ART may be the link between the reported cardiovascular risk and abacavir administration.