BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3, and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

• Klíčová slova
• COVID‐19, Europe, HIV, SARS‐CoV‐2 testing,
• MeSH
• COVID-19 * epidemiologie   diagnóza   MeSH
• dospělí MeSH
• HIV infekce * farmakoterapie   epidemiologie   MeSH
• hospitalizace * statistika a číselné údaje   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet CD4 lymfocytů MeSH
• rizikové faktory MeSH
• SARS-CoV-2 * MeSH
• senioři MeSH
• testování na COVID-19 statistika a číselné údaje   metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

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.

• Klíčová slova
• CD4 cell count, COVID-19, HIV viral load strata, PLWH, outcomes,
• MeSH
• COVID-19 * epidemiologie   komplikace   MeSH
• HIV infekce * komplikace   farmakoterapie   epidemiologie   MeSH
• lidé MeSH
• počet CD4 lymfocytů MeSH
• respirační insuficience * MeSH
• retrospektivní studie MeSH
• SARS-CoV-2 MeSH
• testování na COVID-19 MeSH
• virová nálož MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• východní Evropa MeSH

Treatment of HIV infection has modified the initially fatal infection into a typically chronic disease requiring lifelong treatment. However, there is no complete normalization of immune activation, signs of inflammation and prothrombotic state in treated patients. This condition is the result of many factors, but the main cause is thought to be the residual production of HIV-1 RNA and viral proteins by infected cells in cellular reservoirs. Persistence of immune activation/inflammation/prothrombotic state leads to the pathophysiology of "sterile inflammation" and so-called non-AIDS diseases, which manifest one to two decades earlier in those infected. Despite all the pitfalls and unwanted secondary manifestations of antiretroviral drugs, the treatment of HIV infection has managed to reverse the trajectory of a fatal pandemic and has made it possible to approach therapeutic modalities that were absolutely unimaginable just a few years ago. Solid organ transplantation is now a completely legitimate therapeutic method for patients living with HIV, and highly suppressive treatment even allows transplantation from an HIV-infected donor. The text below presents a brief overview of the basic pitfalls, but also of the successes, of the current highly suppressive treatment of HIV infection.

• Klíčová slova
• Antiretroviral therapy, HIV, HIV reservoir, Transplantation, immune activacion, non-AIDS diseases, transplantation,
• MeSH
• antiretrovirové látky terapeutické užití   MeSH
• HIV infekce * komplikace   farmakoterapie   MeSH
• HIV-1 * genetika   MeSH
• lidé MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiretrovirové látky MeSH

PURPOSE: We aimed to compare the effects of P-glycoprotein (ABCB1) on the intestinal uptake of tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), and metabolites, tenofovir isoproxil monoester (TEM) and tenofovir (TFV), and to study the molecular mechanism of drug-drug interaction (DDI) between sofosbuvir (SOF) and TDF/TAF. METHODS: Bidirectional transport experiments in Caco-2 cells and accumulation studies in precision-cut intestinal slices prepared from the ileal segment of rodent (rPCIS) and human (hPCIS) intestines were performed. RESULTS: TDF and TAF were extensively metabolised but TAF exhibited greater stability. ABCB1 significantly reduced the intestinal transepithelial transfer and uptake of the TFV(TDF) and TFV(TAF)-equivalents. However, TDF and TAF were absorbed more efficiently than TFV and TEM. SOF did not inhibit intestinal efflux of TDF and TAF or affect intestinal accumulation of TFV(TDF) and TFV(TAF)-equivalents but did significantly increase the proportion of absorbed TDF. CONCLUSIONS: TDF and TAF likely produce comparable concentrations of TFV-equivalents in the portal vein and the extent of permeation is reduced by the activity of ABCB1. DDI on ABCB1 can thus potentially affect TDF and TAF absorption. SOF does not inhibit ABCB1-mediated transport of TDF and TAF but does stabilise TDF, albeit without affecting the quantity of TFV(TDF)-equivalents crossing the intestinal barrier. Our data thus suggest that reported increases in the TFV plasma concentrations in patients treated with SOF and TDF result either from a DDI between SOF and TDF that does not involve ABCB1 or from a DDI involving another drug used in combination therapy.

• Klíčová slova
• P-glycoprotein, intestinal permeability, sofosbuvir, tenofovir alafenamide fumarate, tenofovir disoproxil fumarate,
• MeSH
• adenin metabolismus   MeSH
• alanin MeSH
• Caco-2 buňky MeSH
• fumaráty MeSH
• HIV infekce * farmakoterapie   MeSH
• látky proti HIV * MeSH
• lidé MeSH
• P-glykoprotein MeSH
• P-glykoproteiny MeSH
• sofosbuvir terapeutické užití   MeSH
• tenofovir MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenin MeSH
• alanin MeSH
• fumaráty MeSH
• látky proti HIV * MeSH
• P-glykoprotein MeSH
• P-glykoproteiny MeSH
• sofosbuvir MeSH
• tenofovir MeSH

AIMS: To analyse the hallmarks of ocular manifestations of and therapeutic modalities for syphilis in the last two decades. The clinical features of syphilitic uveitis, and association with the human immunodeficiency virus (HIV) coinfection are described. METHODS: Retrospective study of 16 patients diagnosed with ocular syphilis confirmed by serological tests in the General University Hospital in Prague between the years 2004 and 2021. General characteristics of ocular and systemic manifestations and visual functions were analysed. RESULTS: An increasing incidence of syphilitic uveitis correlates with a general rise in syphilis cases. In our study, the ocular manifestation of syphilis was panuveitis (44%), posterior uveitis (31%) and anterior uveitis (25%). Posterior uveitis was found in 3 patients (19%) associated with preretinal infiltrates, that are often present in syphilitic uveitis. The worst visual outcomes were among patients with human immunodeficiency virus (HIV) coinfection and/or neurosyphilis, however the data were not significant. Optic disc edema was present in 56%, macular involvement in 37% of patients. Overall, 31% of patients in our cohort had persistent visual field defects due to impairment of their optic nerve or macula despite the final median Snellen visual acuity of 1.0. Two out of sixteen patients were treated with corticosteroids in addition to antibiotics. CONCLUSION: Posterior uveitis with preretinal infiltrates and optic disc edema should arouse suspicion of ocular syphilis. Recent data show the advantages of adjacent systemic corticosteroid treatment for severe forms of syphilitic uveitis and/or neuritis. Our observation supports this finding.

• Klíčová slova
• corticosteroids, optic disc edema, optic neuritis, syphilis, uveitis,
• MeSH
• HIV infekce * komplikace   diagnóza   farmakoterapie   MeSH
• koinfekce * komplikace   MeSH
• lidé MeSH
• městnavá papila * komplikace   MeSH
• oční infekce bakteriální * farmakoterapie   diagnóza   epidemiologie   MeSH
• retrospektivní studie MeSH
• syfilis * komplikace   farmakoterapie   diagnóza   MeSH
• uveitida * farmakoterapie   etiologie   diagnóza   MeSH
• zadní uveitida * komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

• Klíčová slova
• AIDS, Antiretroviral therapy, Drug-induced diabetes, Environmental exposure, HIV, Infectious diseases, Protease inhibitors, Sub-Saharan Africa, Type 2 diabetes mellitus,
• MeSH
• černoši MeSH
• diabetes mellitus * farmakoterapie   epidemiologie   MeSH
• HIV infekce * farmakoterapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Geografické názvy
• subsaharská Afrika epidemiologie   MeSH

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.

• Klíčová slova
• AIDS, COVID-19, Central Europe, Eastern Europe, HIV infection, antiretroviral drugs, antiretroviral therapy, initial therapy, maintenance therapy, rapid ART strategy, southeastern Europe, switch therapy,
• MeSH
• COVID-19 * epidemiologie   MeSH
• HIV infekce * farmakoterapie   epidemiologie   MeSH
• inhibitory proteas terapeutické užití   MeSH
• látky proti HIV * terapeutické užití   MeSH
• lidé MeSH
• pandemie MeSH
• průřezové studie MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• inhibitory proteas MeSH
• látky proti HIV * MeSH

BACKGROUND: Men experience twice the mortality of women while on ART in sub-Saharan Africa (SSA) largely due to late HIV diagnosis and poor retention. Here we propose to conduct an individually randomized control trial (RCT) to investigate the impact of three-month home-based ART (hbART) on viral suppression among men who were not engaged in care. METHODS AND DESIGN: A programmatic, individually randomized non-blinded, non-inferiority-controlled trial design (ClinicalTrials.org NCT04858243). Through medical chart reviews we will identify "non-engaged" men living with HIV, ≥15years of age who are not currently engaged in ART care, including (1) men who have tested HIV-positive and have not initiated ART within 7 days; (2) men who have initiated ART but are at risk of immediate default; and (3) men who have defaulted from ART. With 1:1 computer block randomization to either hbART or facility-based ART (fbART) arms, we will recruit men from 10-15 high-burden health facilities in central and southern Malawi. The hbART intervention will consist of 3 home-visits in a 3-month period by a certified male study nurse ART provider. In the fbART arm, male participants will be offered counselling at male participant's home, or a nearby location that is preferred by participants, followed with an escort to the local health facility and facility navigation. The primary outcome is the proportion of men who are virally suppressed at 6-months after ART initiation. Assuming primary outcome achievement of 24.0% and 33.6% in the two arms, 350 men per arm will provide 80% power to detect the stated difference. DISCUSSION: Identifying effective ART strategies that are convenient and accessible for men in SSA is a priority in the HIV world. Men may not (re-)engage in facility-based care due to a myriad of barriers. Two previous trials investigated the impact of hbART on viral suppression in the general population whereas this trial focuses on men. Additionally, this trial involves a longer duration of hbART i.e., three months compared to two weeks allowing men more time to overcome the initial psychological denial of taking ART.

• MeSH
• HIV infekce * farmakoterapie   MeSH
• látky proti HIV * terapeutické užití   MeSH
• lidé MeSH
• novorozenec MeSH
• poradenství MeSH
• randomizované kontrolované studie jako téma MeSH
• samotestování MeSH
• zdravotnická zařízení MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Malawi MeSH
• Názvy látek
• látky proti HIV * MeSH

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent cornerstones of current regimens for treatment of human immunodeficiency virus type 1 (HIV-1) infections. However, NNRTIs usually suffer from low aqueous solubility and the emergence of resistant viral strains. In the present work, novel bicyclic NNRTIs derived from etravirine (ETV) and rilpivirine (RPV), bearing modified purine, tetrahydropteridine, and pyrimidodiazepine cores, were designed and prepared. Compounds 2, 4, and 6 carrying the acrylonitrile moiety displayed single-digit nanomolar activities against the wild-type (WT) virus (EC50 = 2.5, 2.7, and 3.0 nM, respectively), where the low nanomolar activity was retained against HXB2 (EC50 = 2.2-2.8 nM) and the K103N and Y181C mutated strains (fold change, 1.2-6.7×). Most importantly, compound 2 exhibited significantly improved phosphate-buffered saline solubility (10.4 μM) compared to ETV and RPV (≪1 μM). Additionally, the binding modes of compounds 2, 4, and 6 to the reverse transcriptase were studied by X-ray crystallography.

• MeSH
• HIV infekce * farmakoterapie   MeSH
• HIV reverzní transkriptasa metabolismus   MeSH
• HIV-1 * metabolismus   MeSH
• inhibitory reverzní transkriptasy MeSH
• látky proti HIV * chemie   MeSH
• lidé MeSH
• racionální návrh léčiv MeSH
• rilpivirin terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• etravirine MeSH Prohlížeč
• HIV reverzní transkriptasa MeSH
• inhibitory reverzní transkriptasy MeSH
• látky proti HIV * MeSH
• rilpivirin MeSH

AIM: The aim of the study was to describe the prevalence of HIV-1 subtypes and HIV-1 strains resistant to antiretroviral therapy (ART) in HIV-positive persons newly diagnosed in Slovakia in 2019-2021. MATERIALS AND METHODS: The study group consisted of 184 HIV-positive naïve patients newly diagnosed in Slovakia from 2019 to 2021. The viral HIV-1 RNA was isolated from plasma by the QIAamp Viral RNA Mini Kit (QIAGEN, Germany). For RT-PCR and sequencing of the HIV pol region, in-house procedures were used according to the ANRS AC11 protocol for RT (reverse transcriptase), PRO (protease), and IN (integrase) [ANRS AC11 Resistance Study Group, 2015]. Analysis of sequences was performed using Sequencing Analysis Software v5.3 (Applied Biosystems®). HIV sequences were manually edited using BioEdit (version 7.2.5), compared with consensus HIV-1 sequences in the Los Alamos Sequence Database (URL 2), aligned using CLUSTAL W [Labarga et al., 2007] and BioEdit software packages (version 7.2 .5) [Hall, 1999]. HIVDB Algorithm (version 9.0) of the Stanford HIV Drug resistance database (URL 1.) was used for sequence evaluation. For HIV-1 subtype analysis, the REGA HIV-1 Subtyping Tool [De Oliviera et al., 2005] and phylogenetic analysis MEGA X [Kumar et al., 2018] were used. RESULTS: Phylogenetic analyses performed in samples of 184 persons revealed the most prevalent subtype B (129/184, 70.11%), detected to the greatest extent in the population of men who have sex with men (MSM) (96/129 74.42%). Concerning non-B subtypes (55/184, 29.89%), subtype A was found with the highest prevalence (48/184, 26.09%) compared to subtype F (F1) (3; 1.63%), C (1; 0.54%) and circulating recombinant forms CRF02_AG (2; 1.09%), CRF01_AE (1; 0.54%). In 9.24% (17/184) of samples, 25 mutations clinically relevant and associated with HIV resistance ART were detected, of which 7.07% (13/184) to reverse transcriptase inhibitors, 1.66% (3/181) to protease inhibitors and 1.32% (2/151) to integrase inhibitors. In addition, multiclass resistance was present in 1.63% (3/184) of patients. Mutations associated with HIV resistance to ART were found in 9.30 % of persons infected with subtype B. CONCLUSION: Our study confirmed ongoing highest prevalence of subtype B with a slightly decreasing trend compared to last years. Detection of mutations causing HIV resistance to ART underlines the need for resistance testing in naïve patients even before the initiation of ART in Slovakia.

• MeSH
• fylogeneze MeSH
• genotyp MeSH
• HIV infekce * farmakoterapie   epidemiologie   MeSH
• HIV-1 * genetika   MeSH
• homosexualita mužská MeSH
• lidé MeSH
• mutace MeSH
• sexuální a genderové menšiny * MeSH
• virová léková rezistence genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika epidemiologie   MeSH