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.

Incidence, risk factors, and clinical findings of syphilis among men living with HIV in Croatia during the COVID-19 pandemic.

We conducted a nationwide longitudinal observational study to estimate the incidence of syphilis in a cohort of male persons living with HIV (MLWH) in Croatia in the pre-COVID-19 and COVID-19 years. Data were reviewed and extracted from the clinical database. We analyzed 1187 MLWH (≥ 18 years) in care in Croatia from 2018 to 2021 and used Poisson regression to calculate rates. We observed a 91.4% increase in incidence between 2019 and 2020; the overall rate was 6.0/100 person-years, and the annual rate ranged from 3.3/100 person-years in 2018 to 9.3/100 person-years in 2021. We found higher rates in men who have sex with men, MLWH with a baseline history of syphilis, MLWH with a more recent HIV diagnosis, and a lower rate in those who had clinical AIDS. The rate of syphilis serological testing was 3.5% lower in 2020 compared to 2019. Recurrent syphilis was more likely asymptomatic compared to the first episodes. In conclusion, during the COVID-19 epidemic years, there was a huge increase in syphilis. Results highlight the need for enhanced and novel prevention interventions.

Lupus anticoagulant-hypoprothrombinemia syndrome with severe bleeding diathesis after coronavirus disease 2019: a case report.

Acquired antibodies against factor II (prothrombin) are rare and most commonly associated with severe liver disease or vitamin K antagonist treatment. In very rare cases, these antibodies and associated hypoprothrombinemia are found in patients with lupus anticoagulant (LAC), an antiphospholipid antibody that inhibits phospholipid-dependent coagulation tests. This uncommon entity, called lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), may cause both severe, life-threatening bleeding and a predisposition to thrombosis. Coronavirus disease 2019 (COVID-19) is associated with a variety of coagulation abnormalities and an increased risk of thrombosis. Bleeding may occur, but it is less common than thromboembolism and has mostly been described in association with the severity of the disease and anticoagulation treatment in hospitalized patients, rarely in the post-acute phase of the disease. We report on a case of an 80-year-old man who developed LAHPS with prothrombin antibodies and severe bleeding after COVID-19.

Digital technology and HIV, HCV and STI voluntary counselling and testing: good practice example from Croatia.

The aim of this paper is to introduce the digitalization process and its effects on better reach of the target population. Progress in the digitalization and e-health tools worldwide enables new opportunities in prevention, diagnostics and treatment for people living with HIV (PLHIV) and people in the risk of HIV infection, hepatitis C (HCV) and other sexually transmitted infections (STIs), especially in the context of the COVID-19 pandemic. The system already used for voluntary counselling and testing (VCT) at the CheckPoint Centre Zagreb run by the non-governmental organization (NGO) Croatian Association for HIV and Viral Hepatitis (CAHIV) was upgraded and adapted (due to the COVID-19 prevention epidemiological measures) and developed for implementation of the pilot project of feasibility and acceptability of home HIV self-testing (HIVST) among men who have sex with men (MSM) in Zagreb. A special feature of the HIVST mobile application enables an innovative approach in collecting clients' test result feedback. This paper presents the method of use digitalization of the VCT and HIVST activities to support and increase availability of screening testing. Described procedures of new technologies application in VCT services and preliminary results of the HIVST pilot project indicate that technology-delivered interventions can contribute and improve access and utilisation of HIV/STI prevention and care services.

Correction: Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020.

[This corrects the article DOI: 10.1371/journal.pone.0263437.].

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.

Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020.

BACKGROUND: During the initial phase of the COVID-19 pandemic, there was great enthusiasm for the use of azithromycin with or without hydroxychloroquine. OBJECTIVES: We analyzed azithromycin consumption in Croatia in 2020 and compared this to the period 2017-2019. METHODS: Azithromycin consumption was evaluated using the IQVIA Adriatic d.o.o. database which collects data on azithromycin distribution from wholesale pharmacies to hospital and non-hospital pharmacies in Croatia. We analyzed data for the period from January 2017 to December 2020. Azithromycin distribution was measured as days of therapy (DOT) and reported as per 1000 inhabitants or per 1000 inhabitant-days. RESULTS: In the period 2017-2020, total azithromycin DOT in Croatia increased in 2017, 2018, 2019, and 2020 (1.76, 1.91, 1.91 and 2.01/1000 inhabitant-days, respectively). Non-hospital pharmacies received 2.18 times and hospital pharmacies 4.39 times more DOT units/1000 inhabitants of azithromycin in March 2020 compared to the average distribution rate in March 2017-2019. During the peak of the COVID-19 epidemic (November and December 2020) azithromycin distribution increased considerably in hospital (3.62 and 3.19 times, respectively) and non-hospital pharmacies (1.93 and 1.84 times, respectively) compared to the average consumption in the same months in 2017-2019. CONCLUSIONS: Our data showed increased azithromycin distribution in the period 2017-2020 which indicates azithromycin overuse. Preliminary information on COVID-19 treatments with a desire to offer and try what is available even in the absence of strong scientific evidence may have influenced practices of antimicrobial prescriptions.

Hepatitis A Outbreak in Men Who Have Sex with Men Using Pre-Exposure Prophylaxis and People Living with HIV in Croatia, January to October 2022.

The hepatitis A virus (HAV) is a highly hepatotropic virus transmitted mainly via the fecal-oral route. The purpose of this study is to describe a prolonged HAV outbreak in HIV-infected men who have sex with men (MSM) and pre-exposure prophylaxis (PrEP) users in Croatia in 2022. Croatia has a centralized system of HIV care and the PrEP service is only available at the University Hospital for Infectious Diseases (UHID), Zagreb. We reviewed all MSM living with HIV and MSM PrEP users at UHID and identified those diagnosed with HAV between January and October 2022. During this period, a total of 1036 MSM living with HIV and 361 PrEP users were followed, and 45 (4.4%) and 32 (8.9%) were diagnosed with HAV, respectively. Most cases were diagnosed in mid-February. A total of 70.1% (726/1036) MSM living with HIV and 82.3% (297/361) PrEP users were susceptible to HAV. Sequencing information was available for 34 persons; in all cases the HAV subtype IA was found. Our findings indicate that both MSM living with HIV and HIV-uninfected PrEP users are vulnerable to HAV infection and might be a potential source for a more widespread HAV epidemic.

Timeliness of antiretroviral therapy initiation in the era before universal treatment.

We assessed the prevalence and factors related to the time to antiretroviral (ART) initiation among persons who entered HIV care and subsequently started ART in Croatia from 2005 to 2014. Included were patients ≥ 18 years, the follow-up ended on Dec/31/2017. 628 patients were included into the study 91.9% were men; median age was 36.1 (Q1-Q3: 29.6-43.8) years. Rapid (within 7 days of diagnosis) ART initiation was observed in 21.8% patients, 49.8% initiated ART within 30 days, 21.7% and 28.5% had intermediate (31 days-1 year) and late initiation (> 1 year), respectively. Of 608 patients that achieved an undetectable viral load, 94% had a plasma HIV-1 RNA < 50 copies/ml at last measurement after a median follow-up of 5.2 years. On quantile regression analysis, calendar year of entry into care, and markers of more advanced HIV disease (higher viral load, lower CD4 cell count and clinical AIDS) were significantly associated with earlier ART initiation. Early ART was not related to a gap in care afterwards at all quantiles. In conclusion, a significant proportion of patients started ART early in Croatia in 2005-2014. Early ART initiation led to durable viral load suppression and was not associated with a subsequent gap in care.

Evaluation of platelet count and platelet function analyzer - 100 testing for prediction of platelet transfusion following coronary bypass surgery.

Platelet transfusions are commonly administered to treat bleeding in cardiac surgery. The aim of this study was to compare platelet (PLT) count and values of collagen adenosine diphosphate closure time (cADP-CT) measured by Platelet Function Analyzer (PFA) for prediction of PLT transfusion therapy following coronary bypass surgery. For this prospective observational study, 66 patients scheduled for coronary artery bypass grafting (CABG) who received early PLT transfusions (within 60 min after the operation) were enrolled. To assess changes in platelets, count and function, two time points were selected: 15 min before and 30 - 60 min after the end of PLT transfusion. The patients were divided into transfused and non-transfused with further PLT in the 48 h postoperatively. We used the receiver operating characteristics (ROC) curve to investigate whether the PLT count and cADP-CT values were predictors of PLT transfusion. The positive predictive values (PPV) of PLT count and cADP-CT after PLT transfusion for further PLT transfusion were 33% and 86% respectively, with a PLT count threshold of ≤200 × 109/L and cADP-CT threshold of ≥118 s. The comparison among the ROC curves showed a statistical difference (p = .0002). In multiple regression analysis, cADP-CT was the strongest predictor for the number of PLT transfusion doses in the 48 h postoperatively. In CABG patients, the results of cADP-CT after PLT transfusion have a better predictive capacity for further PLT transfusions than the PLT count.

Successful treatment of genotype 3 hepatitis C infection in a noncirrhotic HIV infected patient on chronic dialysis with the combination of sofosbuvir and velpatasvir: A case report.

RATIONALE: Data on anti-HCV therapy in patients on dialysis is still evolving. Sofosbuvir is mainly eliminated through the renal route and there is controversy about its use in these patients. PATIENT CONCERNS: We describe a 53-year-old male patient with HCV genotype 3 and human immunodeficiency type 1 (HIV) infection on chronic dialysis. HIV infection was diagnosed in 1987 and since July 2007 the patient was compliant with his antiretroviral therapy (ART) and had an undetectable plasma HIV viral load on all follow-up measurements. The patient was known to have HCV infection since 1997 but has never been treated for chronic hepatitis C. Because of progressive renal impairment dialysis started in 2005. DIAGNOSIS: Before anti-HCV treatment commenced the patient liver transient elastography (FibroScan) indicated F3 fibrosis (stiffness, 11.6 kPa) and his HCV RNA viral load was 320,798 IU/mL (Abbott RealTime HCV assay). INTERVENTION: Fixed dose combination of sofosbuvir/velpatasvir (400 mg/100 mg) for 11 weeks. OUTCOMES: Twelve weeks after treatment cessation HCV RNA was undetectable, hence the patient achieved a sustained virologic response. The drugs were well tolerated and the patient did not report any side effects. LESSONS: Sofosbuvir/velpatasvir may be an option for HCV genotype 3 infection in patients coinfected with HIV on long-term dialysis.

The Role of Platelet Function Analyzer Testing in Cardiac Surgery Transfusion Management.

BACKGROUND: Identifying high-risk patients for transfusion after cardiac operations would alter postoperative management. The aim of this study was to investigate closure time (CT) measured by platelet function analyzer (PFA) for prediction of bleeding and transfusions. METHODS: 66 patients were scheduled for coronary artery bypass graft (CABG) surgery and 30 patients for valve repair and replacement (non-CABG). Measurements of PFA-100® CT for collagen and adenosine diphosphate (cADP) and collagen and epinephrine (cEPI) were performed 15 min after protamine administration. Blood loss was measured, and the amount of transfusion products was recorded postoperatively. RESULTS: The study demonstrated significant differences between CABG patients with cADP-CT ≥ 118 s and those with cADP-CT < 118 s with regard to blood loss for 24 h (p = 0.001) and blood loss for 25-48 h (p = 0.003) as well as fresh frozen plasma (p = 0.015), platelet (p > 0.001) and red blood cell (p = 0.002) units given in 48 postoperative h. There were no differences cardiopulmonary bypass when was applied. In non-CABG patients, there were no differences in blood loss and transfusion requirements with respect to cADP-CT and cEPI-CT. CONCLUSION: Postoperative platelet dysfunction measured by a prolonged cADP-CT was significant predictor of blood loss and transfusion in CABG patients.