HIV disease metrics and COVID-19 infection severity and outcomes in people living with HIV in central and eastern Europe.

BACKGROUND: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS-CoV-2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID-19 severity in this cohort. METHODS: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID-19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID-19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1. RESULTS: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID-19 diagnosis was 605 cells/µL [interquartile range (IQR) 409-824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/µL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001). CONCLUSION: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID-19 illness and can be used as a prognostic indicator in this cohort.

Mapping frailty in people living with HIV: A nationwide study in Greece.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

HIV treatment strategies across Central, Eastern and Southeastern Europe: New times, old problems.

INTRODUCTION: In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region. RESULTS: In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons. CONCLUSIONS: In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

New Insights into the Fluid Management in Patients with Septic Shock.

The importance of fluid resuscitation therapy during the early stages of sepsis management is a well-established principle. Current Surviving Sepsis Campaign (SSC) guidelines recommend the early administration of intravenous crystalloid fluids for sepsis-related hypotension or hyperlactatemia due to tissue hypoperfusion, within the first 3 h of resuscitation and suggest using balanced solutions (BSs) instead of normal saline (NS) for the management of patients with sepsis or septic shock. Studies comparing BS versus NS administration in septic patients have demonstrated that BSs are associated with better outcomes including decreased mortality. After initial resuscitation, fluid administration has to be judicious in order to avoid fluid overload, which has been associated with increased mortality, prolonged mechanical ventilation, and worsening of acute kidney injury. The "one size fits all" approach may be "convenient" but it should be avoided. Personalized fluid management, based on patient-specific hemodynamic indices, provides the foundations for better patient outcomes in the future. Although there is a consensus on the need for adequate fluid therapy in sepsis, the type, the amount of administered fluids, and the ideal fluid resuscitation strategy remain elusive. Well-designed large randomized controlled trials are certainly needed to compare fluid choices specifically in the septic patient, as there is currently limited evidence of low quality. This review aims to summarize the physiologic principles and current scientific evidence regarding fluid management in patients with sepsis, as well as to provide a comprehensive overview of the latest data on the optimal fluid administration strategy in sepsis.

Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock-inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Chems4EU: chemsex use and its impacts across four European countries in HIV-positive men who have sex with men attending HIV services.

INTRODUCTION: Chemsex in a European context is the use of any of the following drugs to facilitate sex: crystal methamphetamine, mephedrone and gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) and, to a lesser extent, cocaine and ketamine. This study describes the prevalence of self-reported recreational drug use and chemsex in HIV-positive men who have sex with men (MSM) accessing HIV services in four countries. It also examines the problematic impacts and harms of chemsex and access to chemsex-related services. METHODS: This is a cross-sectional multi-centre questionnaire study of HIV-positive MSM accessing nine HIV services in the UK, Spain, Greece and Italy. RESULTS: In all, 1589 HIV-positive MSM attending HIV services in four countries completed the questionnaire. The median age of participants was 38 years (interquartile range: 32-46 years) and 1525 (96.0%) were taking antiretroviral therapy (ART). In the previous 12 months, 709 (44.6%) had used recreational drugs, 382 (24.0%) reported chemsex and 104 (6.5%) reported injection of chemsex-associated drugs ('slamsex'). Of the 382 engaging in chemsex, 155 (40.6%) reported unwanted side effects as a result of chemsex and 81 (21.2%) as a result of withdrawal from chemsex. The reported negative impacts from chemsex were on work (25.1%, 96), friends/family (24.3%, 93) and relationships (28.3%, 108). Fifty-seven (14.9%) accessed chemsex-related services in the past year, 38 of whom (67%) felt the service met their needs. DISCUSSION: A quarter of participants self-reported chemsex in the past 12 months. There were high rates of harms from chemsex across all countries, including negative impacts on work, friends/family and relationships. Although a minority of those engaging in chemsex accessed support, most found this useful.

Earlier treatment initiation is associated with a decreased number of HIV-1 subtype A1 transmissions in Greece.

OBJECTIVES: Subtypes 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. METHODS: Our 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. RESULTS: A 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. CONCLUSIONS: Our 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.

Identifying, linking, and treating people who inject drugs and were recently infected with HIV in the context of a network-based intervention.

Identifying and linking people to care soon after HIV infection could limit viral transmission and protect their health. This work aims at describing the continuum of care among recently HIV-infected people who inject drugs (PWID) and participated in an intervention in the context of an HIV outbreak in Athens, Greece. The Transmission Reduction Intervention Project (TRIP) conducted risk network-based contact tracing and screened people for recent HIV infection. A comprehensive approach with a case management component that aimed to remove barriers to accessing care was adopted. Follow-up data on antiretroviral treatment (ART) and HIV-RNA levels were obtained from HIV clinics. TRIP enrolled 45 recently HIV-infected PWID (80% male) with a median viral load at recruitment of 5.43 log10 copies/mL. Of the recently infected persons in TRIP, 87% were linked to care; of these, 77% started ART; and of those on ART, 89% achieved viral load <200 copies/mL. TRIP and its public health allies managed to get most of the recently HIV-infected PWID who were identified by the program into care and many of them onto ART. This resulted in very low HIV-RNA levels. Treatment as prevention can work if individuals are aided in overcoming difficulties in entry to, or attrition from care.

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review.

Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and has markedly improved the disease burden and life expectancy of people living with HIV. HIV enters the central nervous system (CNS) early in the course of infection, establishes latency, and produces a pro-inflammatory milieu that may affect cognitive functions, even in the cART era. Whereas severe forms of neurocognitive impairment (NCI) such as HIV-associated dementia have declined over the last decades, milder forms have become more prevalent, are commonly multifactorial, and are associated with comorbidity burdens, mental health, cART neurotoxicity, and ageing. Since 2007, the Frascati criteria have been used to characterize and classify HIV-associated neurocognitive disorders (HAND) into three stages, namely asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). These criteria are based on a comprehensive neuropsychological assessment that presupposes the availability of validated, demographically adjusted, and normative population data. Novel neuroimaging modalities and biomarkers have been proposed in order to complement NCI assessments, elucidate neuropathogenic mechanisms, and support HIV-associated NCI diagnosis, monitoring, and prognosis. By integrating neuropsychological assessments with biomarkers and neuroimaging into a holistic care approach, clinicians can enhance diagnostic accuracy, prognosis, and patient outcomes. This review interrogates the value of these modes of assessment and proposes a unified approach to NCI diagnosis.

HCV Cascade of Care in HIV/HCV Co-Infected Individuals: Missed Opportunities for Micro-Elimination.

People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals living in Greece and investigated factors associated with different HCV-CoC stages. We analyzed data from 1213 participants from the Athens Multicenter AIDS Cohort Study. A seven-stage CoC, overall and by subgroup (people who inject drugs (PWID), men having sex with men (MSM), men having sex with women (MSW), and migrants], was constructed, spanning from HCV diagnosis to sustained virologic response (SVR). Logistic/Cox regression models were employed to identify factors associated with passing through each CoC step. Among 1213 anti-HCV-positive individuals, 9.2% died before direct-acting antiviral (DAA) availability. PWID exhibited higher mortality rates than MSM. Of 1101 survivors, 72.2% remained in care and underwent HCV-RNA testing. Migrants and PWID showed the lowest retention rates. HCV-RNA was available for 79.2% of those in care, with 77.8% diagnosed with chronic HCV. Subsequently, 71% initiated DAAs, with individuals with very low CD4 counts (<100 cells/µL) exhibiting lower odds of DAA initiation. SVR testing was available for 203 individuals, with 85.7% achieving SVR. The SVR rates did not differ across risk groups. In 2023, significant gaps and between-group differences persisted in HCV-CoC among HIV-HCV co-infected individuals in Greece.

Mpox across countries from Central and Eastern Europe - 2022 outbreak.

BACKGROUND: The aim of the study was to assess socio-demographical characteristics, clinical presentation, and outcomes in patients diagnosed with mpox. METHODS: A survey on patients diagnosed with mpox was performed in 14 countries from Central and Eastern Europe. Data was compared according to HIV status and country of origin (EU vs. non-EU). Mpox diagnosis was confirmed by RT-PCR from oropharyngeal swabs, skin lesions, and other body fluids. RESULTS: Out of 154 patients confirmed with mpox in 2022, 99.3% were males, with a median age (years) of 35 (IQR 30-39), 90.2% MSM and 48.7% PLWH. Compared to HIV-negative subjects, PLWH had more frequent high-risk behaviours:chemsex (p = 0.015), group sex (p = 0.027), and a history of sexually transmitted infections (STIs) (p = 0.004). Persons from EU were more often PLWH (p = 0.042), MSM (p < 0.0001), had multiple sexual partners (p = 0.025), practiced chemsex (p = 0.008) or group-sex (p = 0.005) and had more often history of STIs (p < 0.0001). The median CD4 cell count/mL at mpox diagnosis was 713 (IQR 486-996) and 73.5% had undetectable HIV VL. The commonest clinical features were fever (108 cases), lymphadenopathy (78), and vesiculo-pustular rash: penile (76), perianal (48), limbs (67). Fifty-one (31%) persons were hospitalized due to complications or epidemiological reasons. Three patients received tecovirimat or cidofovir. The outcome was favorable for all patients, including 4 with severe forms. CONCLUSIONS: Mpox was diagnosed predominantly in young MSM, with high-risk behaviors and history of STIs. Effective contact tracing and vaccination are important strategic pillars to control mpox outbreaks.

Switching from Tenofovir Disoproxil to Tenofovir Alafenamide Fumarate: Impact on Cardiovascular Risk and Lipid Profile in People Living with HIV, an Observational Study.

In the era of combination antiretroviral therapy (ART), people living with HIV (PLHIV) still face an increased risk of cardiovascular disease (CVD). Tenofovir alafenamide fumarate (TAF) is superior to its precursor tenofovir disoproxil fumarate (TDF) regarding bone and renal toxicity, but there are concerns about a negative effect on lipid profile. This observational, single-center study investigates the effects on lipid profile and cardiovascular (CVD) risk of the switch from TDF to TAF, in combination with emtricitabine/elvitegravir/cobicistat (FTC/EVG/c), in patients with no exposure to other antiretrovirals. Routine laboratory measurements, somatometric characteristics, and smoking status were analyzed for the assessment of CVD risk changes, using D:A:D and ATP III scores pre- and postswitch. A total of 62 patients with a mean age of 32.9 years were included in this study. Sixty-one patients (98.4%) were men, 38 (61.3%) late presenters, and 39 (62.9%) active smokers. A year after the switch, there was a significant increase in total cholesterol (178 ± 38 to 194 ± 40 mg/dL, p < .001), high-density lipoprotein (45 ± 12 to 48 ± 13 mg/dL, p = .001), and low-density lipoprotein (117 ± 32 to 137 ± 36 mg/dL, p < .001). Mean increase of the 10-year D:A:D score was 1.13% (95% confidence interval, 1.05-1.22, p = .002). Changes were more prominent in nonsmokers. Body mass index and average weight showed an upward trend. Switching from TDF to TAF caused significant changes in lipid profile at 14 months of follow-up, in young, otherwise healthy PLHIV. CVD risk, as measured by D:A:D, showed a statistically significant increase, but more data are needed to determine clinical significance. These results point toward a patient-centered approach when selecting an ART regimen.

The impact of frailty and illness perceptions on quality of life among people living with HIV in Greece: A network analysis.

OBJECTIVE: Despite the significant advances in healthcare, people living with HIV still face challenges that affect their quality of life (QoL), both in terms of their physical state as represented by frailty and of their illness perceptions (IP). The aim of this study was to unravel the associations between these constructs (QoL, frailty, IP). METHODS: This multicenter, cross-sectional study included 477 people living with HIV (93% male; median age = 43 years, IQR = 51.7) from six HIV clinics in Greece. Frailty phenotype, QoL and IP were assessed using Fried's criteria, EuroQoL (EQ-5D-5L) and Brief Illness Perception Questionnaire (BIPQ), respectively. Network analysis model was utilized. RESULTS: Among frailty criteria, exhaustion had the highest expected influence, while the strongest correlation concerns exhaustion and weak grip strength (pr = 0.14). Regarding the QoL items, usual activities displayed the highest expected influence. The correlations of pain/discomfort with mobility (pr = 0.31), and usual activities with self-care (pr = 0.34) were the strongest. For the BIPQ items, the strongest correlation was found between illness concern and emotional response (pr = 0.45), whereas the latter item was the one that displayed the highest expected influence. Three communities were formed: 1) personal control, treatment control and coherence, 2) the frailty items with mobility, self-care, usual activities, and pain/discomfort, and 3) the rest BIPQ items with anxiety/depression. Identity displayed the highest bridge strength, followed by pain/discomfort, usual activities and consequences. CONCLUSIONS: The interplay between QoL, frailty, and IP in people living with HIV requires clinical attention. Self-reported exhaustion, slow walking speed, and low physical activity affect the physical QoL dimensions, while anxiety/depression is strongly associated with illness-related concern and perceived emotional effects, leading to psychological distress. Symptom management can improve QoL, and information on the disease and treatment can enhance control over the disease. Developing interventions to address QoL, frailty, and IP is crucial.

Endothelial Glycocalyx Integrity in Treatment-Naïve People Living with HIV before and One Year after Antiretroviral Treatment Initiation.

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed EG at baseline, 24 (±4) and 48 (±4) weeks, by measuring the perfused boundary region (PBR, inversely proportional to EG thickness), in sublingual microvessels. In total, 66 consecutive PLWH (60 (90.9%) males) with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40(60.6%) received INSTI-based regimens. The mean (standard deviation) PBR decreased significantly from 2.17 (0.29) µm at baseline to 2.04 (0.26) µm (p = 0.019), and then to 1.93 (0.3) µm (p < 0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. PLWH on INSTIs had a significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low levels of viremia experienced the greatest PBR reduction. This study is the first to report the benefit of antiretroviral treatment on EG improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH.

Association of Mal/TIRAP S180L variant polymorphism with decreased infection risk in patients with advanced HIV-1 infection.

OBJECTIVES: MyD88 adaptor-like (Mal/TIRAP) is an adaptor protein bridging activation of Toll-like receptors 2 and 4 after stimulation by exogenous and endogenous ligands. We investigated the association between the presence of the S180L SNP of Mal and the risk of severe infection in individuals with human immunodeficiency virus (HIV)-1 infection. METHODS: The SNP S180L was determined in a cohort of 179 HIV-1 infected Greek patients. Analysis of the prevalence of this SNP in relation to the infectious complications was evaluated. RESULTS: One hundred and thirty-two (73.3%) patients were bearing the wild type haplotype, 43 (24%) were heterozygous for the SNP, and four (2.2%) were homozygous for the variant allele. The individuals with a nadir CD4 count <200 cells/mm(3) who carried the 180L variant demonstrated a 4-fold decrease in the odds ratio (OR) for any serious infection compared with those who carried the wild-type 180S genotype (OR 0.58 vs OR 2.6, p=0.016). CONCLUSIONS: This study suggest a protection effect of the Mal S180L SNP against serious infections in HIV-1 infected individuals with low CD4 cell counts.

Sexualized Drug Use and Chemsex: Their Association with Sexual Health Among Men who have Sex with Men Living in Greece.

Objectives: The study aims to investigate rates of sexualized drug use (SDU) and chemsex, a type of SDU involving specifically the use of crystal methamphetamine, mephedrone, or GHB/GBL and their association with the rates of negative sexual health outcomes among men who have sex with men (MSM) in Greece. Methods: Survey of 485 MSM in internal disease departments and community testing centers. Results: Twenty-eight percent of participants were involved in SDU and 20.4% in chemsex. HIV positive status and recent STI diagnoses were associated with SDU involvement. Conclusion: SDU and chemsex rates and their impact on health reveal the need for informed community-based services.

An exploration of the quality of life of people living with HIV in Greece: Challenges and opportunities.

OBJECTIVE: Improving 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. DESIGN: Twenty-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. RESULTS: First, 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). CONCLUSIONS: Empowering 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.

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Early alterations of the innate and adaptive immune statuses in sepsis according to the type of underlying infection.

INTRODUCTION: Although major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time. METHODS: The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer. RESULTS: Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis. CONCLUSIONS: Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.