Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. METHODS: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. RESULTS: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/µL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. CONCLUSIONS: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

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.

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.

HCV reinfection after HCV therapy among HIV/HCV-coinfected individuals in Europe.

OBJECTIVES: Although direct-acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV-coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV-coinfected individuals in Europe. METHODS: Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV-RNA test and 2 years follow-up were assessed using logistic regression. RESULTS: Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43-54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)-free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7-8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11-0.38; 0.43, 95% CI: 0.22-0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. CONCLUSIONS: Among HIV/HCV-coinfected individuals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV.

National strategies for vaccination against COVID-19 in people living with HIV in Central and Eastern European region.

INTRODUCTION: People living with HIV (PLWH) are at higher risk of poorer COVID-19 outcomes. Vaccination is a safe and effective method of prevention against many infectious diseases, including COVID-19. Here we investigate the strategies for national COVID-19 vaccination programmes across central and eastern Europe and the inclusion of PLWH in vaccination programmes. METHODS: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of infectious diseases from 24 countries in the region. Between 1 November 2020 and 19 March 2021 the group proceeded an on-line survey consisting of 20 questions. RESULTS: Twenty-two countries (out of 24 invited) participated in the survey and 20/22 countries in the period between December 2020 and March 2021 had already started their COVID-19 vaccination programme. In total, seven different vaccines were used by participating countries. In 17/21 countries (81%), vaccinated persons were centralized within the national registry. In 8/21 countries (38%) PLWH were prioritized for vaccination (the Czech Republic, Greece, Hungary, Lithuania, Montenegro, Romania, Slovakia, Slovenia) and the Czech Republic, Greece and Serbia had put in place national guidelines for vaccination of PLWH. In 14/20 countries (70%) vaccination was only provided by designated centres. Eighteen respondents (18/21; 85.7%) reported that they planned to follow up HIV patients vaccinated against COVID-19, mainly by measuring antibody levels and checking COVID-19 incidence (11/21; 52.3%). CONCLUSIONS: This survey-based study suggests that there are significant differences in terms of prioritizing PLWH, the types of vaccines used, vaccination coverage, and the development and implementation of a vaccination programmes within the region. Regardless of heterogenicity and existing barriers within the region, systematic vaccination in PLWH should have the highest priority, especially in those with severe immunodeficiency, risk factors, and in the elderly, aiming for prompt and high vaccination coverage.

Retrospective evaluation of an observational cohort by the Central and Eastern Europe Network Group shows a high frequency of potential drug-drug interactions among HIV-positive patients receiving treatment for coronavirus disease 2019 (COVID-19).

OBJECTIVES: The aim of this international multicentre study was to review potential drug-drug interactions (DDIs) for real-life coadministration of combination antiretroviral therapy (cART) and coronavirus disease 2019 (COVID-19)-specific medications. METHODS: The Euroguidelines in Central and Eastern Europe Network Group initiated a retrospective, observational cohort study of HIV-positive patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data were collected through a standardized questionnaire and DDIs were identified using the University of Liverpool's interaction checker. RESULTS: In total, 524 (94.1% of 557) patients received cART at COVID-19 onset: 117 (22.3%) were female, and the median age was 42 (interquartile range 36-50) years. Only 115 (21.9%) patients were hospitalized, of whom 34 required oxygen therapy. The most frequent nucleoside reverse transcriptase inhibitor (NRTI) backbone was tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide (TAF) with lamivudine or emtricitabine (XTC) (79.3%) along with an integrase strand transfer inhibitor (INSTI) (68.5%), nonnucleoside reverse transcriptase inhibitor (NNRTI) (17.7%), protease inhibitor (PI) (13.7%) or other (2.5%). In total, 148 (28.2%) patients received COVID-19-specific treatments: corticosteroids (15.7%), favipiravir (7.1%), remdesivir (3.1%), hydroxychloroquine (2.7%), tocilizumab (0.6%) and anakinra (0.2%). In total, 62 DDI episodes were identified in 58 patients (11.8% of the total cohort and 41.9% of the COVID-19-specific treatment group). The use of boosted PIs and elvitegravir accounted for 43 DDIs (29%), whereas NNRTIs were responsible for 14 DDIs (9.5%). CONCLUSIONS: In this analysis from the Central and Eastern European region on HIV-positive persons receiving COVID-19-specific treatment, it was found that potential DDIs were common. Although low-dose steroids are mainly used for COVID-19 treatment, comedication with boosted antiretrovirals seems to have the most frequent potential for DDIs. In addition, attention should be paid to NNRTI coadministration.

Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium.

OBJECTIVE: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. RESULTS: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND.

National medical specialty guidelines of HIV indicator conditions in Europe lack adequate HIV testing recommendations: a systematic guideline review.

BackgroundAdequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing.AimTo evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries.MethodsBetween 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty).ResultsOf 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines.ConclusionFewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

National multi-stakeholder meetings: a tool to support development of integrated policies and practices for testing and prevention of HIV, viral hepatitis, TB and STIs.

BACKGROUND: Country level policies and practices of testing and care for HIV, viral hepatitis and sexually transmitted infections are lagging behind European recommendations on integration across diseases. Building on previous experiences and evidence, the INTEGRATE Joint Action arranged four national stakeholder meetings. The aim was to foster cross-disciplinary and cross-disease collaborations at national level as a vehicle for strengthened integration of testing and care services. This article presents the methodology and discusses main outcomes and recommendations of these meetings. METHODS: Local partners in Croatia, Italy, Lithuania and Poland oversaw the planning, agenda development and identification of key persons to invite to ensure that meetings addressed main challenges and issues of the respective countries. Invited national stakeholders represented policy and public health institutions, clinical settings, testing sites and community organisations. National experts and experts from other European countries were invited as speakers and facilitators. Main topic discussed was how to increase integration across HIV, viral hepatitis and sexually transmitted infections in testing and care policies and practice; tuberculosis was also addressed in Lithuania and Italy. RESULTS: The agendas reflected national contexts and the meetings provided a forum to engage stakeholders knowledgeable of the national prevention, testing and care systems in interaction with international experts who shared experiences of the steps needed to achieve integration in policies and practice. The evaluations showed that participants found meetings relevant, important and beneficial for furthering integration. Of the respondents 78% agreed or strongly agreed that there was a good representation of relevant national stakeholders, and 78% that decision/action points were made on how to move the agenda forward. The importance of securing participation from high level national policy makers was highlighted. Outcomes were nationally tailored recommendations on integrated policies and strategies, diversification of testing strategies, stigma and discrimination, key populations, cost effectiveness, surveillance and funding. CONCLUSIONS: Shifting from single to multi-disease approaches require collaboration among a broad range of actors and national multi-stakeholder meetings have proven excellent to kick-start this. Face-to-face meetings of key stakeholders represent a unique opportunity to share cross-sectoral perspectives and experiences, identify gaps in national policies and practices and agree on required next steps.

Routine HIV testing program in the University Infectious Diseases Centre in Lithuania: a four-year analysis.

BACKGROUND: HIV transmission remains a major concern in Eastern Europe, and too many people are diagnosed late. Expanded testing strategies and early and appropriate access to care are required. Infectious disease departments might be targets for expanded HIV testing owing to the intense passage of key patient populations that carry indicators of HIV disease. Our objective was to evaluate the feasibility and clinical effectiveness of a fully integrated, opt-out routine, rapid HIV testing program. METHODS: A retrospective four-year study of a screening program was conducted from 2010 through 2014. The program was divided into two periods: from 2010 to 2012 (pilot study) and from 2013 to 2014. The pilot study consisted of routine HIV testing of patients aged 18-55 that were hospitalized in one department. In the second period, all inpatients aged 18-65 were eligible. Targeted testing was conducted in the other inpatient department during the pilot study and the outpatient department during both periods. RESULTS: During the pilot study, 2203 patients were hospitalized, 1314 (59.6%) were eligible, 954 (72.6%) were tested, and 3 (0.31%) were newly diagnosed HIV-positive. In the second period, 4911 patients were hospitalized, 3727 (75.9%) were eligible, 3303 (88.6%) were tested, and 7 (0.21%) were HIV-positive. In total, 2800 targeted tests were performed, and 4 (0.14%) patients tested positive with newly discovered HIV. All 14 newly diagnosed patients were provided with care. Comparing cumulative groups of routine and targeted testing, the HIV prevalence was 0.23% vs. 0.14% (p = 0.40) and was above the reported cost-effectiveness threshold of 0.1% (p = 0.012). A lower proportion of advanced disease and a higher proportion of heterosexually transmitted infection were found in the routine testing group. CONCLUSION: Routine HIV testing in admissions of infectious diseases is acceptable, feasible, sustainable and clinically effective. Compared to targeted testing, routine testing helped to discover more patients in earlier stages and those with heterosexually transmitted HIV infection.

Successful use of extracorporeal membrane oxygenation in a human immunodeficiency virus infected patient with severe acute respiratory distress syndrome.

INTRODUCTION: We report a case of an adult patient with human immunodeficiency virus (HIV), acute respiratory distress syndrome (ARDS) and ventilator associated pneumonia (VAP) caused by multidrug resistant (MDR) bacteria that was successfully managed with veno-venous extracorporeal membrane oxygenation (ECMO). CASE REPORT: A 25 year old male with no significant past medical history had been admitted to a local hospital due to dyspnea and fever. His pulmonary function subsequently failed necessitating mechanical ventilation (MV) and introduction of ECMO support. The patient was transported for 300 km by road on ECMO to a tertiary medical center. The diagnosis of ARDS, HIV infection and MDR bacterial and fungal VAP was made. Patient was successfully treated with antiretroviral therapy (ART), anti-infective agents and 58 days of veno-venous ECMO support, with complete resolution of the respiratory symptoms. CONCLUSION: HIV infected patients with ARDS and MDR bacterial VAP whose HIV replication is controlled by ART could be successfully managed with ECMO.

The socio-demographic, clinical characteristics and outcomes of tuberculosis among HIV infected adults in Lithuania: A thirteen-year analysis.

BACKGROUND: Tuberculosis (TB) is a public health problem in Lithuania, among the 18 high-priority TB countries in the European region, and the most common AIDS-indicative disease with the highest proportion in the EU/EEA since 2015. The study aimed to identify socio-demographic, clinical characteristics and their relationship with TB outcomes in TB-HIV co-infected patients in Lithuania. METHODS: A retrospective chart review analysed the characteristics of TB-HIV co-infected adults registered in State Information System of Tuberculosis over 2008-2020. The factors associated with drug-resistant TB and unsuccessful treatment outcome were identified by multivariable logistic regression. RESULTS: The study included 345 cases in 311 patients (239 new, 106 previously treated cases), median age 40 years (IQR 35-45), 80.7% male. 67.8% patients knew their HIV-positive status before TB diagnosis, median time to TB diagnosis was 8 years (IQR 4-12). 83.6% were unemployed, 50.5%-anytime intravenous drug users (IDU), 34.9% abused alcohol. Drug-resistant TB rates in new and previously treated TB cases were 38.1% and 61.3%, respectively. In multivariable analysis, higher risk of drug-resistant TB was associated with imprisonment in new (aOR 3.35; 95%CI 1.17-9.57) and previously treated (aOR 6.63; 95%CI 1.09-40.35) cases. In 52.3% of new TB cases and in 42.5% previously treated TB cases the treatment outcomes were unsuccessful. In multivariable analysis of new TB cases, current imprisonment (aOR 2.77; 95%CI 1.29-5.91) and drug-resistant TB (aOR 2.18; 95%CI 1.11-4.28) were associated with unsuccessful treatment outcome. In multivariable analysis of previously treated TB cases, female gender (aOR 11.93; 95%CI 1.86-76.69), alcohol abuse (aOR 3.17; 95%CI 1.05-9.58), drug-resistant TB (aOR 4.83; 95%CI 1.53-15.28) were associated with unsuccessful treatment outcome. CONCLUSIONS: In the TB-HIV-infected adult cohort in Lithuania, unemployment, imprisonment, IDU, alcohol abuse, known to be risk factors for TB, were very frequent. Drug resistance was an undeniable risk factor for unsuccessful treatment outcome and imprisonment was associated with drug resistant TB.

Latent Tuberculosis Infection and Associated Risk Factors among People Living with HIV and HIV-Uninfected Individuals in Lithuania.

BACKGROUND: People living with HIV (PLHIV) with latent tuberculosis infection (LTBI) are at increased risk of tuberculosis (TB) reactivation compared to the HIV-negative population. Lithuania belongs to the 18 high-priority TB countries in the European region. The aim of this study was to compare the prevalence of LTBI and LTBI-related risk factors between PLHIV and HIV-uninfected populations. METHODS: A cross-sectional study was conducted in three Lithuanian Infectious Diseases centres from August 2018 to May 2022 using the interferon gamma release assay (IGRA) and tuberculin skin test (TST) in Vilnius, and IGRA only in Siauliai and Klaipeda. Cohen's kappa was used to assess IGRA and TST agreement. A structured questionnaire was completed by the study participants. LTBI-related risk factors were identified using a multivariable logistic regression model. RESULTS: In total, 391 PLHIV and 443 HIV-uninfected individuals enrolled, with a median age of 41 (IQR 36-48) and 43 (IQR 36-50), consisting of 69.8% and 65.5% male, respectively. The prevalence of LTBI defined by positive IGRA and/or TST among PLHIV was higher compared to that in the HIV-uninfected population (20.5% vs. 15.3%; OR 1.42; 95% CI 1.02-2.03; p = 0.04). The concordance between IGRA and TST was fair: kappa = 0.23 (95% CI 0.09-0.34). In multivariable analyses, association with injecting drug use (IDU) (ORa 2.25, 95% CI 1.27-3.99, p = 0.01) and imprisonment (ORa 1.99, 95% CI 1.13-3.52, p = 0.02) in all participants, IDU (ORa 2.37, 95% CI 1.09-5.15; p = 0.029) in PLHIV and a history of contact with an active TB patient (ORa 3.33, 95% CI 1.53-7.24; p = 0.002) in HIV-uninfected individuals were significant associations evidenced by LTBI. CONCLUSIONS: The prevalence of LTBI among PLHIV in Lithuania is higher compared to that in the HIV-uninfected population and the European average. The association with IDU in PLHIV emphasizes the need for integrated HIV, TB and substance abuse treatment to provide patient-centred care.

Vaccination against HBV and HAV as Mode of Hepatitis Prevention among People Living with HIV-Data from ECEE Network Group.

(1) Background: Viral hepatitis C (HCV) and viral hepatitis B (HBV) are common co-infections in people living with HIV (PLWH). All PLWH should be vaccinated against HBV and hepatitis A (HAV) and treated for HBV and HCV. We aimed to compare testing, prophylaxis and treatment of viral hepatitis in PLWH in Central and Eastern Europe (CEE) in 2019 and 2022. (2) Methods: Data was collected through two on-line surveys conducted in 2019 and 2022 among 18 countries of the Euroguidelines in CEE (ECEE) Network Group. (3) Results: In all 18 countries the standard of care was to screen all PLWH for HBV and HCV both years; screening of HAV was routine in 2019 in 54.5% and in 2022 47.4% of clinics. Vaccination of PLWH against HAV was available in 2019 in 16.7%, in 2022 in 22.2% countries. Vaccination against HBV was available routinely and free of charge in 50% of clinics both in 2019 and 2022. In HIV/HBV co-infected the choice of NRTI was tenofovir-based in 94.4% of countries in both years. All clinics that responded had access to direct-acting antivirals (DAAs) but 50% still had limitations for treatment. (4) Conclusions: Although testing for HBV and HCV was good, testing for HAV is insufficient. Vaccination against HBV and especially against HAV has room for improvement; furthermore, HCV treatment access needs to overcome restrictions.

PrEP Scale-Up and PEP in Central and Eastern Europe: Changes in Time and the Challenges We Face with No Expected HIV Vaccine in the near Future.

With no expected vaccine for HIV in the near future, we aimed to define the current situation and challenges for pre- and post-exposure prophylaxis (PrEP and PEP) in Central and Eastern Europe (CEE). The Euroguidelines CEE Network Group members were invited to respond to a 27-item survey including questions on PrEP (response rate 91.6%). PrEP was licensed in 68.2%; 95 centers offered PrEP and the estimated number on PrEP was around 9000. It was available in daily (40.1%), on-demand (13.3%), or both forms (33.3%). The access rate was <1−80%. Three major barriers for access were lack of knowledge/awareness among people who are in need (59.1%), not being reimbursed (50.0%), and low perception of HIV risk (45.5%). Non-occupational PEP was available in 86.4% and was recommended in the guidelines in 54.5%. It was fully reimbursed in 36.4%, only for accidental exposures in 40.9%, and was not reimbursed in 22.72%. Occupational PEP was available in 95.5% and was reimbursed fully. Although PrEP scale-up in the region has gained momentum, a huge gap exists between those who are in need of and those who can access PrEP. Prompt action is required to address the urgent need for PrEP scale-up in the CEE region.

Two dog-related infections leading to death: overwhelming Capnocytophaga canimorsus sepsis in a patient with cystic echinococcosis.

Capnocytophaga canimorsus is a fastidious, capnophilic, fusiform, and filamentous gram-negative rod. It is part of the normal oral flora of dogs and cats and can cause an infection in humans, but is of generally low virulence in healthy individuals. A case of fatal sepsis due to Capnocytophaga canimorsus in a 46-year-old woman with clinically silent cystic echinococcosis discovered postmortem is present. She had been bitten by a dog 3 days before the symptoms appeared. The family had owned the dog for 4 years. A preliminary diagnosis of septic shock of unknown etiology with multisystem organ failure was established. Despite all the efforts, the patient died on the seventh day of hospitalization. Laboratory findings received postmortem showed Capnocytophaga canimorsus isolated from the blood culture after 7 incubation days. Autopsy showed a cyst in the liver with a fibrotic wall and necrotic eosinophilic interiors containing fragments of Echinococcus granulosus scolices. In conclusion, an interaction possibly established long ago between the host and Echinococcus granulosus conditioned immunosuppression mechanisms developed by the parasite in this case, which can explain such an aggressive course of the infection with Capnocytophaga. Two dog-related infections were fatal in the middle-aged dog owner considered healthy before this hospitalization. Vigilance concerning recent exposure to dogs or cats and potential immunosuppression risk factors must be maintained in a patient presenting with clinical features of fulminant sepsis.

Preliminary report on the provision of HIV care to war refugees with HIV who are migrating from Ukraine: data from the ECEE Network Group.

The ECEE Network Group investigated early provision of HIV care to war refugees migrating from Ukraine in Central and Eastern Europe (CEE) through an online survey. Fourteen countries admitting war refugees from Ukraine on March 31, 2022, completed the survey. Most centers (86%) organized provision of same day antiretroviral therapy (ART) for at least 30 days (77%), but indicated that it may affect the local HIV care. CEE countries put effective emergency mechanisms, which need continuation with international support.

The Management of HIV Care Services in Central and Eastern Europe: Data from the Euroguidelines in Central and Eastern Europe Network Group.

INTRODUCTION: The COVID-19 pandemic has been challenging time for medical care, especially in the field of infectious diseases (ID), but it has also provided an opportunity to introduce new solutions in HIV management. Here, we investigated the changes in HIV service provision across Central and Eastern European (CEE) countries before and after the COVID-19 outbreak. METHODS: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of ID from 24 countries within the CEE region. Between 11 September and 29 September 2021, the group produced an on-line survey, consisting of 32 questions on models of care among HIV clinics before and after the SARS-CoV-2 outbreak. RESULTS: Twenty-three HIV centers from 19 countries (79.2% of all countries invited) participated in the survey. In 69.5% of the countries, there were more than four HIV centers, in three countries there were four centers (21%), and in four countries there was only one HIV center in each country. HIV care was based in ID hospitals plus out-patient clinics (52%), was centralized in big cities (52%), and was publicly financed (96%). Integrated services were available in 21 clinics (91%) with access to specialists other than ID, including psychologists in 71.5% of the centers, psychiatrists in 43%, gynecologists in 47.5%, dermatologists in 52.5%, and social workers in 62% of all clinics. Patient-centered care was provided in 17 centers (74%), allowing consultations and tests to be planned for the same day. Telehealth tools were used in 11 centers (47%) before the COVID-19 pandemic outbreak, and in 18 (78%) after (p = 0.36), but were represented mostly by consultations over the telephone or via e-mail. After the COVID-19 outbreak, telehealth was introduced as a new medical tool in nine centers (39%). In five centers (28%), no new services or tools were introduced. CONCLUSIONS: As a consequence of the COVID-19 pandemic, tools such as telehealth have become popularized in CEE countries, challenging the traditional approach to HIV care. These implications need to be further evaluated in order to ascertain the best adaptations, especially for HIV medicine.

Chronic Kidney Disease and Nephrology Care in People Living with HIV in Central/Eastern Europe and Neighbouring Countries-Cross-Sectional Analysis from the ECEE Network.

Chronic kidney disease (CKD) is a significant cause of morbidity and mortality among patients infected with human immunodeficiency virus (HIV). The Central and East Europe (CEE) region consists of countries with highly diversified HIV epidemics, health care systems and socioeconomic status. The aim of the present study was to describe variations in CKD burden and care between countries. The Euroguidelines in the CEE Network Group includes 19 countries and was initiated to improve the standard of care for HIV infection in the region. Information on kidney care in HIV-positive patients was collected through online surveys sent to all members of the Network Group. Almost all centres use regular screening for CKD in all HIV (+) patients. Basic diagnostic tests for kidney function are available in the majority of centres. The most commonly used method for eGFR calculation is the Cockcroft-Gault equation. Nephrology consultation is available in all centres. The median frequency of CKD was 5% and the main cause was comorbidity. Haemodialysis was the only modality of treatment for kidney failure available in all ECEE countries. Only 39% of centres declared that all treatment options are available for HIV+ patients. The most commonly indicated barrier in kidney care was patients' noncompliance. In the CEE region, people living with HIV have full access to screening for kidney disease but there are important limitations in treatment. The choice of dialysis modality and access to kidney transplantation are limited. The main burden of kidney disease is unrelated to HIV infection. Patient care can be significantly improved by addressing noncompliance.

The Presence of Either Typical or Atypical Radiological Changes Predicts Poor COVID-19 Outcomes in HIV-Positive Patients from a Multinational Observational Study: Data from Euroguidelines in Central and Eastern Europe Network Group.

HIV-positive patients may present lungs with multiple infections, which may hinder differential diagnoses and the choice of treatment in the course of COVID-19, especially in countries with limited access to high-standard healthcare. Here, we aim to investigate the association between radiological changes and poor COVID-19 outcomes among HIV-positive patients from Central and Eastern Europe. Between November 2020 and May 2021, the Euroguidelines in Central and Eastern Europe Network Group started collecting observational data on HIV and COVID-19 co-infections. In total, 16 countries from Central and Eastern European submitted data (eCRF) on 557 HIV-positive patients. The current analyses included patients who had a radiological examination performed. Logistic regression models were used to identify the factors associated with death, ICU admission, and partial recovery (poor COVID-19 outcomes). Factors that were significant in the univariate models (p < 0.1) were included in the multivariate model. Radiological data were available for 224 (40.2%) patients, 108 (48.2%) had computed tomography, and 116 (51.8%) had a chest X-ray. Of these, 211 (94.2%) were diagnosed using RT-PCR tests, 212 (94.6%) were symptomatic, 123 (55.6%) were hospitalized, 37 (16.6%) required oxygen therapy, and 28 (13.1%) either died, were admitted to ICU, or only partially recovered. From the radiologist's description, 138 (61.6%) patients had typical radiological changes, 18 (8.0%) atypical changes, and 68 (30.4%) no changes. In the univariate models, CD4 count (OR = 0.86 [95% CI: 0.76−0.98]), having a comorbidity (2.33 [1.43−3.80]), HCV and/or HBV co-infection (3.17 [1.32−7.60]), being currently employed (0.31 [0.13−0.70]), being on antiretroviral therapy (0.22 [0.08−0.63]), and having typical (3.90 [1.12−13.65]) or atypical (10.8 [2.23−52.5]) radiological changes were all significantly associated with poor COVID-19 outcomes. In the multivariate model, being on antiretroviral therapy (OR = 0.20 [95% CI:0.05−0.80]) decreased the odds of poor COVID-19 outcomes, while having a comorbidity (2.12 [1.20−3.72]) or either typical (4.23 [1.05−17.0]) or atypical (6.39 [1.03−39.7]) radiological changes (vs. no changes) increased the odds of poor COVID-19 outcomes. Among HIV patients diagnosed with symptomatic SARS-CoV-2 infection, the presence of either typical or atypical radiological COVID-19 changes independently predicted poorer outcomes.