SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

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.

Where are we with pre-exposure prophylaxis use in Central and Eastern Europe? Data from the Euroguidelines in Central and Eastern Europe (ECEE) Network Group.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) for HIV infection is an important intervention for control of the HIV epidemic. The incidence of HIV infection is increasing in the countries of Central and Eastern Europe (CEE). Therefore, we investigated the change in PrEP use in CEE over time. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care for HIV and viral hepatitis infections in CEE. Data on access to PrEP were collected from 23 countries through online surveys in May-June 2017 (76 respondents) and in November 2018-May 2019 (28 respondents). RESULTS: About 34.2% of respondents stated that tenofovir/emtricitabine (TDF/FTC) was licensed for use in their country in 2017, and 66.7% that it was licensed for use in 2018 (P = 0.02). PrEP was recommended in national guidelines in 39.5% of responses in 2017 and 40.7% in 2018 (P = 0.378). About 70.7% of respondents were aware of "informal" PrEP use in 2017, while 66.6% were aware of this in 2018 (P = 0.698). In 2018, there were 53 centres offering PreP (the highest numbers in Poland and Romania), whereas six countries had no centres offering PreP. The estimated number of HIV-negative people on PreP in the region was 4500 in 2018. Generic TDF/FTC costs (in Euros) ranged from €10 (Romania) to €256.92 (Slovakia), while brand TDF/FTC costs ranged from €60 (Albania) to €853 (Finland). CONCLUSIONS: Although the process of licensing TDF/FTC use for PrEP has improved, this is not yet reflected in the guidelines, nor has there been a reduction in the "informal" use of PrEP. PrEP remains a rarely used preventive method in CEE countries.

Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe.

OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan-Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches. RESULTS: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. CONCLUSIONS: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.

Alveolar echinococcosis - a rare disease with differential diagnostic problems.

INTRODUCTION: Alveolar echinococcosis is a life-threatening zoonotic parasitic disease. Its incidence is rare. In some cases, the correct and timely diagnosis can be difficult. CASE REPORT: The authors present the case of a young patient with liver, diaphragm and lung involvement. The suspicion of echinococcus infection was made on the basis of medical history, clinical symptoms, and a combination of ultrasonography, computed tomography, magnetic resonance imaging tests and serological methods. The patient underwent multimodal treatment with albendazole and en-bloc resection of the liver, lung and diaphragm. The definitive diagnosis of alveolar echinococcosis was determined from samples of the resected tissues using histopathology and polymerase chain reaction methods. The patient has been followed regularly and is on life-long treatment with albendazole. CONCLUSION: The precise diagnosis and multimodal therapy of alveolar echinococcosis is fundamental from the point of view of patient long-term survival. KEY WORDS: alveolar echinococcosis - diagnosis - multimodal treatment - follow-up.

[Guidelines for caring for HIV-infected adults and postexposure prophylaxis for HIV infection]. / Doporuceny postup pece o dospele infikovane HIV a postexpozicni profylaxe infekce HIV.

The authors present instructions for providing antiretroviral therapy in the Czech health care system, based partly on recommendations from abroad and partly on their own experiences of caring for HIV /AIDS patients. The structure and content are similar to those in the 2010 edition, with new study outcomes and modern trends in treatment strategy being taken into consideration. The guidelines are based on systematic patient assessment and aimed at making an accurate diagnosis and formulating recommendations according to individual criteria. The document provides specific instructions for decisions on initiating antiretroviral therapy, selection of individual drugs, monitoring of treatment effect and adverse reactions, and reaction to potential therapy failure. Special attention is paid to administration of antiretroviral drugs to pregnant women and patients with comorbidities, especially tuberculosis, hepatitis or renal insufficiency. The new version includes procedures for postexposure prophylaxis for HIV infection. The guidelines are supplemented by a table summary of antiretroviral drugs. The presented document is to be used in negotiations between the association,state authorities and health care payers.

Histamine increases the level of IFNγ produced by HIV-1 specific CTLs and this production depends on total IgE level.

BACKGROUND: The HIV (human immunodeficiency virus) population remains a global concern whose treatment is effective, though not yet optimal. Immune based therapies have thus far been disappointing and still need to be explored further. Based on published data suggesting that the functions of cytotoxic CD8+ T lymphocytes (CTL) can be improved by histamine, we investigated the effect of histamine in vitro on HIV-1 specific CD8+ T lymphocytes in HIV+ subjects. RESULTS: 60 HIV+ subjects were included in the study. We evaluated CTL function by IFNγ (interferon gamma) production (using the enzyme-linked immunospot assay (Elispot), BD Bioscience). Changes in the production of IFNγ after incubation with histamine were compared with the levels of total IgE (immunoglobulin E, measured using a Dade Behring analyzer), because histamine is endogenously released through IgE. Activation of HIV-specific CTL by histamine occurs via H2R (histamine receptors). Thus we attempted to block this activation using cimetidine (antagonist H2R). CONCLUSIONS: We found an increase in IFNγ production after the activation of HIV-1 specific CD8+ T lymphocytes by histamine (this elevation was blocked by cimetidine), furthermore, we demonstrated a negative correlation between the production of IFNγ and levels of total IgE.

Liver abscess in human toxocariasis.

BACKGROUND: Toxocariasis is a parasitic infection caused by Toxocara canis or Toxocara cati. It is distributed worldwide. Liver is the main organ affected by Toxocara infection, typically with multiple eosinophilic infiltrates. Liver abscess formation is a very rare condition. METHOD: The authors report on a case of Toxocariasis infection with abscess formation in the right liver lobe. The diagnosis was made upon patient's history, clinical examination, use of ultrasonography, computed tomography and especially upon positive serologic test and hypereosinophilia. After unsuccessful conservative treatment (Mebendazole, antibiotics and corticoids), right hepatectomy was performed. RESULTS: The postoperative course was complicated by biliary fistula in the resection area. The complication was successfully managed by temporary stent implantation to the left hepatic duct. Six months after the operation, the patient is with no complications. CONCLUSION: Liver abscess formation is a rare condition associated with Toxocara infection. It is still a matter of debate whether liver abscess results from severe parasitic infection or whether human toxocariasis is a predisposing cause of pyogenic liver abscess formation. Liver resection is the only treatment option when sepsis fails to respond to conservative treatment (Fig. 5, Ref. 22).

A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study.

OBJECTIVES: The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures. METHODS: Patients starting a nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow-up started ≥ 3 months after initiation of treatment if viral load was <500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers. RESULTS: A total of 603 patients (21%) started nevirapine-based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non-AIDS-related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high-density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P=0.39). CONCLUSIONS: The long-term durability of nevirapine-based cART, based on risk of all-cause discontinuation and development of long-term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen.

[Recommendation for diagnostics and therapy of toxoplasmosis in persons with HIV infection]. / Doporucený postup diagnostiky a terapie toxoplazmózy u osob s HIV infekcí.

Reactivation of latent toxoplasmosis is a serious complication in patients with deep immunodeficiency, but the disease has a good prognosis if early diagnosed and effectively treated. Definitive etiologic proof of the reactivation may be difficult and thus an empiric method (therapeutic trial) is used for confirmation of the diagnosis in clinical practice. The preferred therapy is a combination of pyrimethamine + sulfadiazine.

[Congenital cytomegalovirus infection]. / Kongenitální cytomegalovirová infekce.

Cytomegalovirus (CMV) belongs to the herpesvirus family. Its distribution is ubiquitous in man and many other mammals. CMV causes a typical cytopathic effect with enlargement of the cells that contain intranuclear and cytoplasmic inclusions. CMV is spread directly or by a contact with secretions. Nosocomial transmission can occur during blood transfusion or organ transplantation. Virus excretion after infection continues for a long time. CMV is the most frequent cause of congenital infections (1-2% children). A foetal infection can lead to a preterm labour. Most of CMV congenital infections are benign, only a small proportion of children develop a disease with sensorineural hearing loss or a life threatening multiorgan disease. The diagnosis can be done on the basis of identification of specific antibodies, virus cultivation and PCR from urine, saliva, blood, and cerebrospinal fluid. An antiviral drug ganciclovir can be used for treatment. Anti-CMV vaccines are under the development. Three cases of a congenital CMV infection are described in the paper.

[Free radicals in immunology and infectious diseases]. / Volné radikály v imunologii a u infekcních chorob.

Free radicals contribute significantly in modification of immune processes and inflammatory reactions. They are produced by activated phagocytes which use them for killing microorganisms. Free radicals facilitate production of cytokines, which are important as modifiers of inflammatory reactions. Formation of free radicals is influenced by antioxidants which can thus modify the intensity of inflammatory reaction and immune response. The authors describe in detail the contribution of free radicals in etiology and pathogenesis of autoimmune diseases including rheumatoid arthritis, multiple sclerosis or amyotrophic lateral sclerosis. The role of free radicals and modifying influence of antioxidants in viral, bacterial, parasitic and mycotic diseases is described in the second part of the review. Finally, influence of free radicals and antioxidants on immunity changes in patients with malignant tumours, during aging and physical exercise is discussed.

[Status of HIV-positive persons followed at the AIDS Center of the Medical School Hospital in Pilsen]. / Aktuální stav HIV-pozitivních osob sledovaných v AIDS centru Fakultní nemocnice v Plzni.

The AIDS centre for the western Bohemian region was established at the Infectious Diseases Clinic of the Plzen Faculty Hospital in 1993 but since 1986 the Clinic looks after HIV-positive patients. By Dec. 31, 1996 23 HIV-positive patients were on the records of the centre, the majority having dispensary care. Two patients met the criteria for stage C3 according to CDC (Center for Disease Control), i.e. AIDS. One of them died from generalized cytomegalovirus infection (CMV). Nine subjects are in stage B, the remainder are still asymptomatic. In the submitted paper the authors analyze the health status of different patients with regard to special features of infectious complications in these subjects.

[Changes in clinical and epidemiologic characteristics in Western Bohemia of invasive meningococcal disease associated with the occurrence of an invasive clone of Neisseria meningitidis]. / Zmeny klinických a epidemiologických charakteristik invazivního meningokokového onemocnení v západních Cechách v souvislosti s výskytem invazivního klonu Neisseria meningitidis.

The authors analyzed the incidence of meningococcal diseases in the West Bohemian region in 1982-1996. The draw attention to changes of clinical and epidemiological characteristics of the disease which appeared in 1994 in conjunction with a new invasive clonus of Neisseria meningitidis C:2a:P1.2, P1.5, ET-15/37. While in 1982-1993 invasive meningococcal diseases had in 75% the course of meningitis with a relatively low fatality (4%), during the subsequent period a marked change occurred. Since 1994 the disease took in the West Bohemian region in 58% the course of sepsis with a fatality of 16%. 25% cases of meningococcal meningitis were diagnosed combined sepsis and meningitis in 17%. The disease lost its seasonal character and the authors confirmed the highest incidence of the disease in the age group from 15-19 years and 0-4 years. Neisseria meningitidis group C was detected in 1994-1996 in 73% and the invasive clone C:2a:P1.2, P1.5, ET-15/37 in 62%.

Physician documentation of family alcohol problems.

This study was conducted to determine whether family medicine residents' documentation of patient and family alcohol problems corresponded with patients' assessments. A random sample of 180 patient charts from a university-based family practice was audited and 78% (n = 140) of these patients participated in telephone interviews. Of those who participated in the telephone interview, 40% (n = 56) reported a positive family history of drinking problems, 28% (n = 39) indicated that they were currently concerned about the alcohol use of someone in their family, and 24% (n = 34) reported that at least one family member currently had an alcohol problem. Ninety-six percent (n = 134) of the subjects indicated that they believed physicians should ask about family alcohol problems and 91% (n = 128) believed physicians could be helpful in alcohol treatment at least some of the time. The audit of the 180 medical records indicated that residents charted a positive family history on 13% (n = 23) of the records and noted impact upon the family due to a member's drinking in 2% (n = 4) of the records. The study revealed that residents frequently did not identify alcohol problems or related family difficulties and highlighted the need for training and education in this area.

Esophageal obstruction as a sequela to ruptured esophagus in a goat.

Granulation tissue as a sequela to ruptured esophagus was diagnosed as the cause of esophageal obstruction and regurgitation in a 3.5-year-old Toggenburg buck. Thoracic radiography was useful in localization of the problem. The condition was successfully treated by removal of the granulation tissue through left-sided thoracotomy.

[Immunologic risks in patients after splenectomy]. / Imunologická rizika u nemocných po splenektomii.

The more frequent incidence of infections after splenectomy, some leading even to OPSI syndrome, is known from the literature and practice. The authors investigated in two groups of 20 splenectomized patients (on account of injury of the spleen or for haematological reasons) in particular changes of immunological indicators. On both groups they revealed a predominating increase of the absolute number of leucocytes, lymphocytes, the phagocytic index of PMN leucocytes, the ratio of active nucleoli, FW. They found also in both groups a predominating reduction of the number of T lymphocytes (p less than 0.05), with a high probability also NK cells, and a reduction of the late type reactivity of the skin test (Immunoskin test USOL, Praha). In patients splenectomized on account of injury the number of B lymphocytes was raised in 50% of the patients. In both groups of patients IgG serum levels were elevated, alpha-1-antitrypsin and haptaglobin levels were reduced. The CRP level in patients with haematological diagnoses was elevated as compared with the group of patients splenectomized on account of injury (p less than 0.05). In both groups after splenectomy a greater susceptibility to respiratory infections was found. On examination patients with a greater risk were detected and included under dispensary care.

A framework for relating alcoholism and depression.

A diagnosis of primary, as opposed to secondary, depression in alcoholics is not easy to make and not always a helpful clinical guide when it is made. A useful framework for understanding alcoholism and depression clinically is to distinguish between alcoholics who are actively drinking, newly sober, or in recovery. Medication for depression should never be given to an actively drinking alcoholic. Newly sober alcoholics and those in various stages of recovery are expected to be depressed. Medication is generally not needed to deal with depression due either to withdrawal or to life problems associated with recovery from alcoholism. The use of antidepressant medication may be appropriate only when depression continues after all other avenues of therapy have been exhausted.