Search

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. [ABSTRACT FROM AUTHOR]

Objectives: Individuals with HIV infection are at an increased risk for a number of infectious diseases, some of which are preventable by vaccination. Unfortunately, little is known about the attitudes of this population group to vaccination, therefore, we decided to find out vaccination coverage against 5 infections among newly diagnosed HIV-infected patients in the Czech Republic.Methods: This cross-sectional study was conducted on newly diagnosed patients who started their follow-up care at the HIV Clinic of Na Bulovce Hospital during the two following years. Vaccination history data and results of serological tests were collected from all participants.Results: Enrolled were 269 HIV-positive subjects (94.1% males) with a mean age of 34.4 years, 64 subjects (23.8%) had tertiary education, 229 (85.1%) were men having sex with men, 32 (11.9%) were heterosexual, and 8 (3.0%) were injection drug users. The mean CD4+ T-lymphocyte count was 556.2/µL, with 149 persons (55.4%) who had a CD4+ T-lymphocyte count > 500/µL, and 68 (25.3%) individuals were late presenters with CD4+ T-lymphocyte count < 350/µL. A vaccination against tetanus was reported by 262 subjects (97.4%), against influenza by 18 subjects (6.7%), against tick-borne encephalitis by 18 subjects (6.7%), against viral hepatitis A by 78 persons (29.0%), and against hepatitis B by 104 subjects (38.7%). For influenza, tick-borne encephalitis and hepatitis A, a significant positive impact of tertiary education was found (p-values < 0.001-0.044). Vaccination coverage against both types of hepatitis was significantly lower in late presenters (p = 0.044 and p = 0.004, respectively).Conclusions: Vaccination rates found in our cohort were except tetanus and hepatitis B in young people low, especially for influenza and tick-borne encephalitis. Higher level of education and less advanced HIV infection were associated with higher vaccination rates. To improve this unsatisfactory situation, more attention should be paid to vaccination. [ABSTRACT FROM AUTHOR]

HIV infection is often described as a modern‑day scourge of humanity and also the natural consequence of unbridled sexual behavior. In fact, it is a viral infection affecting the human immune system. HIV has spread throughout the world at the end of the last century, causing a pandemic that has so far affected tens of millions of people and has already killed a comparable number. HIV infection can be effectively treated by using antiretrovirals. However, there is still no way to completely eradicate HIV from the human body. Health care for people with HIV infection is concentrated in HIV centers. To provide comprehensive care it is necessary to cooperate with physicians of all specialties, including general practitioners for adults and children. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess the extent of integration of non‐communicable disease (NCD) assessment and management in HIV clinics across Europe. Methods: A structured electronic questionnaire with 41 multiple‐choice and rating‐scale questions assessing NCD assessment and management was sent to 88 HIV clinics across the WHO European Region during March–May 2023. One response per clinic was collected. Results: In all, 51 clinics from 34 countries with >100 000 people with HIV under regular follow‐up responded. Thirty‐seven clinics (72.6%) reported shared NCD care responsibility with the general practitioner. Systematic assessment for NCDs and integration of NCD management were common overall [median agreement 80%, interquartile range (IQR): 55–95%; and 70%, IQR: 50–88%, respectively] but were lowest in central eastern and eastern Europe. Chronic kidney disease (median agreement 96%, IQR: 85–100%) and metabolic disorders (90%, IQR: 75–100%) were regularly assessed, while mental health (72%, IQR: 63–85%) and pulmonary diseases (52%, IQR: 40–75%) were less systematically assessed. Some essential diagnostic tests such as glycated haemoglobin (HbA1c) for diabetes (n = 38/51, 74.5%), proteinuria for kidney disease (n = 30/51, 58.8%) and spirometry for lung disease (n = 11/51, 21.6%) were only employed by a proportion of clinics. The most frequent barriers for integrating NCD care were the lack of healthcare workers (n = 17/51, 33.3%) and lack of time during outpatient visits (n = 12/51, 23.5%). Conclusion: Most HIV clinics in Europe systematically assess and manage NCDs. People with HIV appear to be screened more frequently than the general population at the same age. There are, however, larger gaps among eastern European clinics in general and for clinics in all regions related to mental health, pulmonary diseases and the employment of some essential diagnostic tests. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the effect of human immunodeficiency virus infection on the retinal nerve fibre layer. The thickness was assessed in 48 human immunodeficiency virus--positive patients using scanning laser polarimetry. Results were compared to normal values and tested against factors suspected to affect the retinal nerve fibre layer. The mean value of the thickness was 57.65 ±± 6.18 µµm in our cohort. No significant correlation between the retinal nerve fibre layer thickness and the immune profile or antiretroviral therapy was detected. However, a significant negative correlation between the retinal nerve fibre layer thickness with increasing length of human immunodeficiency virus infection was found. [ABSTRACT FROM AUTHOR]

• What's new? • Currently there is no evidence for a different course of COVID-19 in HIV(+) patients. • This is the first report on COVID-19 among HIV(+) persons in Central and Eastern Europe. • Earlier reports suggested that some antivirals may suppress SARS-CoV-2 replication. • We analyzed a series of 34 cases of HIV and SARS-CoV-2 coinfection. • We found that HIV-related factors are not associated with the course of COVID-19. • Our analysis suggests that antiretrovirals may be associated with the course of COVID-19. There is currently no evidence suggesting that COVID-19 takes a different course in HIV-positive patients on antiretroviral treatment compared to the general population. However, little is known about the relation between specific HIV-related factors and the severity of the COVID-19 disease. We performed a retrospective analysis of cases collected through an on-line survey distributed by the Euroguidelines in Central and Eastern Europe Network Group. In statistical analyses characteristics of HIV-positive patients, asymptomatic/moderate and moderate/severe course were compared. In total 34 HIV-positive patients diagnosed with COVID-19 were reported by 12 countries (Estonia, Czech Republic, Lithuania, Albania, Belarus, Romania, Serbia, Bosnia and Herzegovina, Poland, Russia, Hungary, Bulgaria). Asymptomatic courses of COVID-19 were reported in four (12%) cases, 11 (32%) patients presented with mild disease not requiring hospitalization, moderate disease with respiratory and/or systemic symptoms was observed in 14 (41%) cases, and severe disease with respiratory failure was found in five (15%) patients. The HIV-related characteristics of patients with an asymptomatic/mild course of COVID-19 were comparable to those with a moderate/severe course of COVID-19, except for the use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in cART regimen (0.0% vs. 31.6% respectively, p = 0.0239). In our analyses HIV viral suppression and immunological status were not associated with the course of COVID-19 disease. On the contrary the cART regimen could contribute to severity of SARS-CoV-2 infection. Large and prospective studies are necessary to further investigate this relationship. [ABSTRACT FROM AUTHOR]

Background The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear. Methods Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment). Results A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNA-positive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6–13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7–8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global P  = .33). Hypertension (22.2%; 95% CI, 17.5%–26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%–29.7%) had the largest population-attributable fractions for DM. Conclusions HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus type 1 (HIV-1) latency represents the major barrier to virus eradication in infected individuals because cells harboring latent HIV-1 provirus are not affected by current antiretroviral therapy (ART). We previously demonstrated that DNA methylation of HIV-1 long terminal repeat (5' LTR) restricts HIV-1 reactivation and, together with chromatin conformation, represents an important mechanism of HIV-1 latency maintenance. Here, we explored the new issue of temporal development of DNA methylationinlatentHIV-15' LTR. Results: In the Jurkat CD4+ T cell model of latency, we showed that the stimulation of host cells contributed to de novo DNA methylation of the latent HIV-1 5' LTR sequences. Consecutive stimulations of model CD4+ Tcell line with TNF-α and PMA or with SAHA contributed to the progressive accumulation of 5' LTR DNA methylation. Further, we showed that once established, the highDNAmethylationlevelofthelatent5' LTR in the cell line model was a stable epigenetic mark. Finally, we explored the development of 5' LTR DNA methylation in the latent reservoir of HIV-1-infected individuals who were treated with ART. We detected low levels of 5' LTR DNA methylation in the resting CD4+ Tcellsof the group of patients who were treated for up to 3 years. However, after long-term ART, we observed an accumulation of 5' LTR DNA methylation in the latent reservoir. Importantly, within the latent reservoir of some long-term-treated individuals, we uncovered populations of proviral molecules with a high density of 5' LTR CpG methylation. Conclusions: Our data showed the presence of 5' LTR DNA methylation in the long-term reservoir of HIV-1-infected individuals and implied that the transient stimulation of cells harboring latent proviruses may contribute, at least in part, to the methylation of the HIV-1 promoter. [ABSTRACT FROM AUTHOR]

A relationship between latent toxoplasmosis and the immune system during HIV disease is poorly understood. Therefore, the aim of this follow-up study was to characterize immunological parameters in HIV-infected patients with latent toxoplasmosis and noninfected individuals. A total of 101 HIV-infected patients were enrolled in the study. The patients were classified into two groups based on anti-Toxoplasma gondii antibodies: a group of 55 toxoplasma-positive persons (TP) and a group of 46 toxoplasma-negative persons (TN). Absolute counts of several lymphocyte subsets decreased in the TP group, namely, T cells (p=0.007), B cells (p=0.002), NK cells (p=0.009), CD4 T cells (p=0.028), and CD8 T cells (p=0.004). On the other hand, the percentage of CD8 T cells expressing CD38 and HLA-DR significantly increased during the follow-up in the TP group (p=0.003, p=0.042, resp.) as well as the intensity of CD38 and HLA-DR expression (MFI) on CD8 T cells (p=0.001, p=0.057, resp.). In the TN group, analysis of the kinetics of immunological parameters revealed no significant changes over time. In conclusion, the results suggest that latent T. gondii infection modulates the immune response during HIV infection. [ABSTRACT FROM AUTHOR]

The HLA-B*57:01 allele is associated with a hypersensitivity reaction to abacavir, and its prevalence varies in different populations. The aim of the study was to investigate HLA-B*57:01 prevalence in the Czech HIV-infected population. HLA-B*57:01 prevalence in our cohort was 5.33%, which is similar to the situation in other Central European countries. [ABSTRACT FROM AUTHOR]

Depletion and functional impairment of circulating plasmacytoid dendritic cells (pDCs) are characteristic attributes of HIV-1-infection. The mechanism of dysfunction of pDCs is unclear. Here, we studied the development of phenotype of pDCs in a cohort of HIV-1-infected individuals monitored before the initiation and during a 9-month follow up with antiretroviral therapy (ART). Using polychromatic flow cytometry, we detected significantly higher pDC-surface expression of the HIV-1 receptor CD4, regulatory receptor BDCA-2, Fcγ receptor CD32, pDC dysfunction marker TIM-3, and the marker of killer pDC, TRAIL, in treatment-naïve HIV-1-infected individuals before initiation of ART when compared to healthy donors. After 9 months of ART, all of these markers approached but did not reach the expression levels observed in healthy donors. We found that the rate of decline in HIV-1 RNA level over the first 3 months of ART negatively correlated with the expression of TIM-3 on pDCs. We conclude that immunogenic phenotype of pDCs is not significantly restored after sustained suppression of HIV-1 RNA level in ART-treated patients and that the level of the TIM-3 expressed on pDCs in treatment naïve patients could be a predictive marker of the rate of decline in the HIV-1 RNA level during ART. [ABSTRACT FROM AUTHOR]

HIV pathogenesis includes dysregulated immune responses and cytokines production, resulting in an increased redox stress. Cytokines, namely TNF-alpha, and redox-stress promote replication of HIV-1. We have previously observed that heme arginate, a drug approved for human use in treatment of hepatic porphyria, can reactivate the latent provirus in synergism with PKC inducers like TNF-alpha, phorbol myristate acetate (PMA), prostratin or bryostatin-1, while inhibiting HIV-1 replication during the acute infection. Heme is physiologically decomposed by action of heme oxygenases into 3 degradation products: iron (Fe2+), carbon monoxide (CO) and biliverdin that is further converted to bilirubin by biliverdin reductase. Therefore, we have studied the effects of heme degradation products on latent HIV-1 reactivation when added individually to ACH-2 cells harboring integrated HIV-1 provirus or to a clone of Jurkat cells harboring HIV-minivirus expressing EGFP. Addition of iron increased expression of both HIV-1 p24 Ag and EGFP, while addition of a CO-donor or bilirubin decreased the PMA-stimulated p24 and EGFP expression. The reactivation was inhibited by antioxidants N-acetyl cysteine and vitamin E or by an iron chelator desferrioxamine, decreasing iron-induced redox stress. Desferrioxamine also inhibited the effect of heme arginate on latent HIV-1 reactivation. Redox stress was shown to affect epigenetic mechanisms regulating gene expression as well as to activate redox-sensitive transcription factors. Therefore, we propose a model in which redox-modulating agents induce chromatin remodeling, affect binding of specific transcription factors to HIV-LTR and allow HIV-1 expression. These results may point towards a new direction in the latent HIV-1 reactivation and therapy. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To determine the incidence and laboratory characteristics of primary Toxoplasma gondii infection in HIV-infected individuals. Methods: This retrospective study was conducted between 1988 and 2012 on a cohort of 1130 HIV-infected patients at the AIDS Center Prague. Toxoplasma serology, standard laboratory parameters, and health status were evaluated at 3–6-month intervals for all patients. Results: The total person-time of follow-up of patients at risk of Toxoplasma seroconversion was 3046.3 years; there were 14 primary T. gondii infections, yielding an incidence rate of 0.0046 (95% confidence interval 0.0027–0.0078). Most of the subjects were clinically asymptomatic, but in one case seroconversion was accompanied by transient cervical lymphadenopathy. The CD4+ T-lymphocyte count geometric mean increased from 418 (95% confidence interval 303–579) cells/μl before seroconversion to 501 (95% confidence interval 363–691) cells/μl after seroconversion (p = 0.004), while other parameters (CD8+ T-lymphocytes, natural killer cells, viral load, beta2-microglobulin, total immunoglobulins) remained unchanged. As compared to the control group, patients with primary toxoplasmosis had higher initial levels of total immunoglobulins IgA and IgG and a tendency to higher CD8+ T lymphocyte counts. Conclusions: Neither the incidence nor the course of the primary Toxoplasma infection was influenced by the immune status of the patients. Immune parameters of patients with primary Toxoplasma infection did not differ from those of the controls. [ABSTRACT FROM AUTHOR]