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.

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.

High rates of deferring antiretroviral treatment for patients with HIV and substance use disorders: Results from a national sample of HIV physicians in Ukraine.

BACKGROUND: HIV incidence and mortality are increasing in Ukraine despite their reductions globally, in part due to suboptimal antiretroviral therapy (ART) coverage in key populations of people with HIV (PWH) where the epidemic is concentrated. As physicians are gatekeepers to ART prescription, stigma and discrimination barriers are understudied as a key to meeting HIV treatment targets in key populations. METHODS: A national sample (N = 204) of ART-prescribing physicians in Ukraine were surveyed between August and November 2019. Participants underwent a series of randomized, hypothetical HIV clinical scenarios and decided whether to initiate or defer (or withhold) ART. Scenarios varied based on 5 distinct CD4 counts (CD4: 17, 176, 305, 470, or 520 cells/mL) and 10 different PWH key populations. Z scores and McNemar's test for paired samples were used to assess differences between key populations and CD4 count. Feeling thermometers were used to assess stigma-related measures toward key populations among physicians. RESULTS: Physicians were highly experienced (mean = 19 years) HIV treaters, female (80.4%), and trained in infectious diseases (76.5%). Patients who drink alcohol (range: 21.6%-23.5%) or use (PWUD range: 16.7%-20.1%) or inject (PWID range: 15.5%-20.1%) drugs were most likely to have ART deferred, even at AIDS-defining CD4 counts. PWID maintained on methadone, however, were significantly (p<0.001) less likely to have ART deferred compared with those who were not (range: 7.8%-12.7%) on methadone. Men who have sex with men (range: 5.4%-10.8%), transgender women (range: 4.9%-11.3%), sex workers (range: 3.9%-10.3%),and having an HIV-uninfected sex partner (range: 3.9%-9.3%) had the lowest likelihood of ART deferral. Increasing levels of stigma (i.e., feeling thermometers) towards a key population was correlated with ART deferral (i.e., discrimination). CONCLUSIONS: Despite international and Ukrainian guidelines recommending ART prescription for all PWH, irrespective of risk or CD4 count, ART deferral by experienced HIV experts remains high in certain key populations, especially in PWH and substance use disorders. Strategies that initiate ART immediately after diagnosis (i.e., rapid start antiretroviral therapy), independent of risk group, should be prioritized to truly mitigate the current epidemic.

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.

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.

Unified European support framework to sustain the HIV cascade of care for people living with HIV including in displaced populations of war-struck Ukraine.

Ukraine is one of the countries in Europe most affected by HIV. The escalation of open war on the European continent has affected HIV care in Ukraine in an unprecedented way. Treating physicians in Europe have little experience on how to handle HIV-specific care under these circumstances. A framework is urgently needed that both defines and sets out strategies to handle the specific challenges for emergency support for people living with HIV, both those staying in Ukraine and those becoming displaced. The optimal allocation of the few available medical resources, primarily antiretroviral therapy, is necessary to best prevent individual morbidity and achieve population transmission control. Professional HIV networks play a central role to create, optimise, and execute support strategies. Through a rapid literature review we identified the key strategies needed to create a support framework, adapted to Ukraine's HIV epidemiology. We produce a unified support framework aiming to reduce the inevitable impact on Ukraine's HIV care cascade now, and when rebuilding it after the war.