Immunogenicity and safety of rapid scheme vaccination against tick-borne encephalitis in HIV-1 infected persons.

Tick-borne encephalitis (TBE) is a vector-borne infection associated with a variety of potentially serious complications and sequelae. Vaccination against TBE is strongly recommended for people living in endemic areas. There are two TBE vaccination schemes - standard and rapid - which differ in the onset of protection. With vaccination in a rapid schedule, protection starts as early as 4 weeks after the first dose and is therefore especially recommended for non-immune individuals travelling to endemic areas. Both schemes work reliably in immunocompetent individuals, but only little is known about how TBE vaccination works in people with HIV infection. Our aim was to assess the immunogenicity and safety of the rapid scheme of TBE vaccination in HIV-1 infected individuals. Concentrations of TBE-specific IgG > 126 VIEU/ml were considered protective. The seroprotection rate was 35.7% on day 28 and 39.3% on day 60. There were no differences between responders and non-responders in baseline and nadir CD4 + T lymphocytes. No serious adverse events were observed after vaccination. The immunogenicity of the TBE vaccination was unsatisfactory in our study and early protection was only achieved in a small proportion of vaccinees. Therefore, TBE vaccination with the rapid scheme cannot be recommended for HIV-1 infected individuals.

HIV care in times of the COVID-19 crisis - Where are we now in Central and Eastern Europe?

INTRODUCTION: The SARS-CoV-2 pandemic has hit the European region disproportionately. Many HIV clinics share staff and logistics with infectious disease facilities, which are now on the frontline in tackling COVID-19. Therefore, this study investigated the impact of the current pandemic situation on HIV care and continuity of antiretroviral treatment (ART) supplies in CEE countries. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was established in February 2016 to review standards of care for HIV in the region. The group consists of professionals actively involved in HIV care. On March 19, 2020 we decided to review the status of HIV care sustainability in the face of the emerging SARS-CoV-2 pandemic in Europe. For this purpose, we constructed an online survey consisting of 23 questions. Respondents were recruited from ECEE members in 22 countries, based on their involvement in HIV care, and contacted via email. RESULTS: In total, 19 countries responded: Albania, Armenia, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Greece, Hungary, Lithuania, Macedonia, Poland, Republic of Moldova, Russia, Serbia, Turkey, and Ukraine. Most of the respondents were infectious disease physicians directly involved in HIV care (17/19). No country reported HIV clinic closures. HIV clinics were operating normally in only six countries (31.6%). In 11 countries (57.9%) physicians were sharing HIV and COVID-19 care duties. None of the countries expected shortage of ART in the following 2 weeks; however, five physicians expressed uncertainty about the following 2 months. At the time of providing responses, ten countries (52.6%) had HIV-positive persons under quarantine. CONCLUSIONS: A shortage of resources is evident, with an impact on HIV care inevitable. We need to prepare to operate with minimal medical resources, with the aim of securing constant supplies of ART. Non-governmental organizations should re-evaluate their earlier objectives and support efforts to ensure continuity of ART delivery.

HIV health care providers are ready to introduce pre-exposure prophylaxis in Central and Eastern Europe and neighbouring countries: data from the Euroguidelines in Central and Eastern Europe (ECEE) Network Group.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) for HIV infection has been introduced in only a few European countries. We investigated the potential to provide PrEP in the Central and Eastern European region, and in neighbouring countries. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was formed in February 2016 to review standards of care for HIV infection in the region. Information related to PrEP was collected through on-line surveys. Respondents were recruited by ECEE members based on their involvement in HIV care. RESULTS: Seventy-six respondents from 23 countries participated in the survey. Twenty-six (34.2%) respondents reported that PrEP [tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)] was registered by the drug registration authority in their country. Fifty-three (70.7%) respondents reported being aware of 'informal' PrEP use in their country. If they had access to PrEP, 56 (74.7%) would advise its use in their practice. Forty-five (59.2%) respondents had concerns regarding PrEP use, and 10 (13.3%) expressed the need for more training. Most of the respondents (88.2%) would provide PrEP to people with high-risk behaviours. CONCLUSIONS: PrEP is already used informally in some countries in the region. Physicians are keen to use PrEP if and when it is accessible. Obstacles towards implementing PrEP in those countries were mostly related to lack of national guidelines, drug registration and governmental strategy.

The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people.

OBJECTIVES: B-cell dysfunction and activation are thought to contribute to lymphoma development in HIV-positive people; however, the mechanisms are not well understood. We investigated levels of several markers of B-cell dysfunction [free light chain (FLC)-κ, FLC-λ, immunoglobulin G (IgG), IgA, IgM and IgD] prior to lymphoma diagnosis in HIV-positive people. METHODS: A nested matched case-control study was carried out within the EuroSIDA cohort, including 73 HIV-positive people with lymphoma and 143 HIV-positive lymphoma-free controls. Markers of B-cell dysfunction were measured in prospectively stored serial plasma samples collected before the diagnosis of lymphoma (or selection date in controls). Marker levels ≤ 2 and > 2 years prior to diagnosis were investigated. RESULTS: Two-fold higher levels of FLC-κ [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.19, 2.84], FLC-λ (OR 2.15; 95% CI 1.34, 3.46), IgG (OR 3.05; 95% CI 1.41, 6.59) and IgM (OR 1.46; 95% CI 1.01, 2.11) were associated with increased risk of lymphoma > 2 years prior to diagnosis, but not ≤ 2 years prior. Despite significant associations > 2 years prior to diagnosis, the predictive accuracy of each marker was poor, with FLC-λ emerging as the strongest candidate with a c-statistic of 0.67 (95% CI 0.58, 0.76). CONCLUSIONS: FLC-κ, FLC-λ and IgG levels were higher > 2 years before lymphoma diagnosis, suggesting that B-cell dysfunction occurs many years prior to lymphoma development. However, the predictive value of each marker was low and they are unlikely candidates for risk assessment for targeted intervention.

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens.

OBJECTIVES: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. METHODS: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. RESULTS: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). CONCLUSIONS: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.

Effects of heme degradation products on reactivation of latent HIV-1.

Human immunodeficiency virus (HIV-1) infection can be currently controlled by combined antiretroviral therapy, but a sterilizing cure is not achievable as this therapy does not target persistent HIV-1 in latent reservoirs. Therefore, different latency reversal agents are intensively explored in various models. We have previously observed that heme arginate, a drug approved for human use, reveals a strong synergism with PKC inducers in reactivation of the latent provirus. Heme is physiologically decomposed by heme oxygenases into 3 degradation products: iron (Fe2+), carbon monoxide (CO) and biliverdin which is further converted to bilirubin by biliverdin reductase. In this paper, we have studied the effects of individual heme-degradation products on latent HIV-1 reactivation in ACH-2 cells harboring integrated HIV-1 provirus and in H12 clone of Jurkat cells harboring HIV-minivirus expressing EGFP. We employed addition of ascorbate to generate Fe2+, resulting in increased expression of both HIV-1 p24 Ag and EGFP in PMA-stimulated ACH-2 and H12 cells, respectively, as characterized on RNA and protein levels. On the other hand, addition of a CO-donor or bilirubin decreased the p24 expression. The reactivation of latent HIV-1 by iron or heme arginate was inhibited by antioxidant N-acetyl cysteine, or by an iron chelator desferrioxamine, suggesting that the effects were mediated by iron- or heme-induced redox stress. Finally, we demonstrated the stimulatory effects of heme arginate and PMA on HIV-1 expression in peripheral blood mononuclear cells of HIV-infected patients cultured ex vivo. These results may constitute a new direction in the latent HIV-1 reactivation and therapy.

[Toxoplasmosis in immunocompromised patients]. / Toxoplasmóza u imunokompromitovaných pacientu.

In humans, toxoplasmosis mostly occurs as a latent infection, but in immunocompromised individuals, the agent may reactivate and cause severe to life-threatening disease. HIV positive individuals and transplant recipients, in particular hematopoietic stem cell transplant and heart transplant recipients, are at highest risk. The disease most often affects the central nervous system but can involve any organ. Because of the alteration of the immune response in these patients, the serodiagnosis is not reliable and direct detection of the causative agent is needed--namely by microscopy and DNA PCR. If inadequately treated or left untreated, toxoplasmosis generally has a fatal prognosis in immunocompromised patients and therefore, the treatment must be started as early and energetically as possible. The gold standard both in the treatment of reactivation and secondary prophylaxis is the pyrimethamine-sulfadiazine combination while co-trimoxazole can be used in the primary prophylaxis for high-risk patients.

Incidence, immunological and clinical characteristics of reactivation of latent Toxoplasma gondii infection in HIV-infected patients.

To determine changes in incidence of reactivation of Toxoplasma gondii infection, manifesting as toxoplasmic encephalitis, and to assess the immunological mechanisms controlling reactivation in HIV-infected patients, a Czech cohort of 502 HIV/T. gondii co-infected patients was followed for 2909·3 person-years. The incidence of toxoplasmic encephalitis between the periods before and after the introduction of combination antiretroviral therapy (cART) was compared. Toxoplasmic encephalitis was diagnosed in 21 patients. In those patients the geometric mean value of CD4+ T lymphocytes was 12·6 times lower than in patients with non-reactivated T. gondii infection but an additionally significant decline in CD8+ T lymphocytes (3·3-fold) and natural killer cells (4·3-fold) was observed. This confirms the significance of these parameters. A twelvefold decrease in Toxoplasma reactivation incidence (40·2 vs. 3·4/1000 person-years) between monitored periods was seen. In the cART era, Toxoplasma reactivation was observed only in patients with unrecognized HIV infection or refusing therapy.

[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.

First detection of Chlamydia trachomatis LGV biovar in the Czech Republic, 2010-2011.

We present four cases of proctitis in HIV-infected men having sex with men (MSM) living in the Czech Republic. The causative agent in all cases was the lymphogranuloma venereum (LGV) biovar of Chlamydia trachomatis. The spread of proctitis caused by C. trachomatis serovars L1­3 among MSM has been observed in several European countries, the United States and Canada since 2003. To our knowledge, no LGV cases in eastern Europe have been published to date.

[Diagnostic pitfalls of HIV-associated Kaposi's sarcoma]. / Uskalí diagnostiky Kaposiho sarkomu sdruzeného s HIV infekcí.

Kaposi's sarcoma was one of the very first diseases which indicated the advent of the AIDS pandemic. Despite the marked fall in its occurrence thanks to the introduction of the cART, Kaposi's sarcoma remains the most frequent tumour in HIV-positive patients and still represents a major diagnostic and therapeutic problem. Particularly in the early stages both the macroscopic and histopathological picture of Kaposi's sarcoma may be very atypical, which can cause diagnostic difficulties right at the time when an early therapy may be most successful. In order to improve both the diagnostics and therapy of Kaposi's sarcoma, close collaboration between physicians taking care of HIV-positive patients--mainly infectologists, dermatologists and pathologists, is necessary.

[Analysis of a group of HIV positive women who gave birth in the Czech Republic]. / Analýza souboru HIV pozitivních rodicek v Ceské republice.

OBJECTIVE: An analysis of HIV positive women who gave birth between 1st January 1985 to 31st December 2006 in the Czech Republic. SUBJECT: A retrospective descriptive analysis. SETTING: Teaching Hospital Bulovka, 1st Faculty of Medicine, Charles University, Prague. SUBJECT AND METHODS: The study included HIV positive women that gave birth between 1st January 1985 to 31st December 2006 at Bulovka hospital. The group of 62 HIV positive women (including 7 secundiparae) gave birth to 71 new-borns (twice twins). The deliveries were performed by C-section. We interrupted breast-feeding by all these women. RESULTS: All new-borns were born alive, no one had Apgar score less than 7 at five minutes. No congenital disorders were found. Three new-borns were transfered to Intensive care unit for new-born babies, two due to dysmaturity and one due to abstinence syndrome. 3 new-borns out of total 71 new-borns were HIV positive (4.2%). CONCLUSION: Routine prenatal screening for HIV and high-quality cooperation between obstetricians and infection control doctors are the basic condition of low rate of vertical trasmission HIV infection in the Czech Republic.

[Pneumonia in pregnancy]. / Pneumonie v tehotenství.

OBJECTIVE: Review of the latest informations about etiology, patophysiology and management of pulmonal infections in pregnant women. DESIGN: Review. SETTING: Clinic of Obstetrics and Gynecology, 1st Medical Faculty of Charles University and Teaching Hospital Na Bulovce, Praque. METHODS: Summary of datas from articles in scientific press and textbooks, self experience. CONCLUSION: Acute pneumonia of various etiology can be a serious complication in pregnancy. An X-ray photograph has still an unsubstituable part in diagnosis.