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.

Prevalence and the role of CCR5Δ32 heterozygosity in disease progression in HIV positive patients in the Czech Republic

BACKGROUND: Entry of human immunodeficiency virus type 1 (HIV-1) in target cells is enabled by CD4 receptor and one of two co-receptors, CXCR4 or CCR5. Deletion of 32 bp in CCR5 gene (CCR5Δ32) in both alleles provides strong but not absolute resistance to HIV-1 infection and deletion in one allele slows disease progression to AIDS. Here, we analyzed the prevalence and the role of CCR5Δ32 heterozygosity on the disease progression in HIV positive patients in the Czech Republic. PATIENTS AND METHODS: A total of 92 HIV-1 seropositive subjects that included 80 Czech individuals from the AIDS center in the Hospital Na Bulovce in Prague were enrolled in CCR5 genotyping as a part of a study of the role of HIV fitness on disease progression. DNA was extracted from patient's peripheral blood mononuclear cells and subjected to real-time PCR with specific probes detecting wild-type and 32 bp-deleted CCR5 variants. A subgroup of 74 antiretroviral therapy-naive patients with more than one year of follow-up was used to determine the role of the CCR5Δ32 heterozygous phenotype in disease progression. RESULTS: CCR5Δ32 was found heterozygous in 23.8% of 80 Czech HIV-1 seropositive individuals which is very similar to 21% and 24% prevalence reported in HIV negative Czech population. Homozygous mutant variant was not detected. In CCR5Δ32 heterozygous group we observed slightly higher mean CD4+ T-cell count and lower mean plasma viremia levels. CONCLUSIONS: Overall, our study indicates no obvious benefit of CCR5Δ32 heterozygosity on HIV transmission and only small benefit on disease progression in the Czech HIV-1 cohort.

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.

[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.

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change.

OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies. METHODS: A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional demographic variables. Baseline was defined as the date of starting new antiretrovirals. RESULTS: Four hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment, patients who had rebounded in the year prior to baseline had a 2.4-times higher rate of virological failure after baseline (95% CI 1.77-3.26; P<.0001), while there was no increased incidence in patients whose last viral rebound was >3 years prior to baseline [Incidence rate ratio (IRR) 1.06; 95% CI 0.75-1.50; P=0.73] compared with patients who had never virally rebounded. Patients had an 86% (95% CI 1.36-2.55; P<.0001), 53% (95% CI 1.06-2.04; P=0.02) and 5% (95% CI 0.80-1.38; P=0.72) higher virological failure rate after baseline if they were virally suppressed <50%, 50-70% and 70-90% of the time they were on cART prior to baseline, respectively, compared with those virally suppressed >90% of the time. DISCUSSION: Intensive monitoring after a treatment switch is required in patients who have rebounded recently or have a low percentage of time suppressed while on cART. Consideration should be given to increasing the provision of adherence counselling.

Antibody response of HIV-infected patients to latent, cerebral and recently acquired toxoplasmosis.

The aim of this longitudinal study with 626 HIV-infected patients was to evaluate the capability of serological tests in diagnosing the presence of Toxoplasma gondii infection in HIV-infected patients, as well as the potential impact of various treatment regimes on serological results. Low IgG antibody levels and stable or declining titres predominated. IgM positivity occurred in ten patients (one seroconversion, seven latent, two cerebral toxoplasmosis). Complement fixation test (CFT) titres >or=1:32 imply that the relative risk of cerebral toxoplasmosis is 6.84 (95% confidence interval [CI] 1.44-32.5) but with a predictive value of only 14.0% (95% CI 5.3-27.9). Values of specific antibodies are not biassed by antiretroviral treatment and/or prophylaxis for toxoplasmosis, and the detection of specific antibodies is very useful in the identification of T. gondii infection in the HIV-infected population, but the role of serology in predicting the clinical manifestation of T. gondii infection is limited.

Sol-gel-derived iron oxide thin films on silicon: surface properties and interfacial chemistry.

Uniform high-quality iron oxide thin films can be formed from the spin coating of iron oxide/hydroxide sol-gels on a silicon substrate. Thermal processing of the films at temperatures of approximately 300 degrees C results in the transformation of films into a ternary layered structure with iron oxide, Fe(2)O(3), at the surface, characterized by Mossbauer spectroscopy, and reduced, metallic iron characterized by depth profiling of the surface by X-ray photoelectron spectroscopy as a function of Ar(+) etching. Imaging of the etched surface by scanning electron microscopy reveals two distinct regions at the interface, nanoparticles that are very iron-rich separated by an unstructured region that is somewhat less iron-rich. The results demonstrate a synthetic protocol for the spontaneous formaton of a ternary layered structure from a simple one-step preparation.

[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.

[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.

Evaluation of a commercial IgE ELISA in comparison with IgA and IgM ELISAs, IgG avidity assay and complement fixation for the diagnosis of acute toxoplasmosis.

A panel of sera from patients with known case histories representative of acute toxoplasmosis (primarily lymphadenopathy, n = 106), latent toxoplasmosis (asymptomatic, n = 368) and negative samples (n = 54) was used to evaluate the capacity of five serological tests to differentiate among patients with acute or latent toxoplasmosis and non-infected individuals. Positive IgA, IgE and IgM ELISA results and low IgG avidity and complement fixation test (CFT) titres of >or=256 were considered to be indicative of acute toxoplasmosis. The most sensitive methods were IgM ELISA (98.1%) and CFT (97.1%), albeit with low specificity (65.0% and 64.5%, respectively) and positive predictive values (43.3% and 42.7%, respectively). IgG avidity assay and IgE ELISA had the highest specificity (97.7% and 91.7%, respectively) and the highest positive predictive values (89.4% and 75.6%, respectively). The best association between serological results and clinical findings was obtained with IgE ELISA (86%, as expressed via Youden's index). In a subset of 259 samples categorised by the period between the onset of clinical symptoms and sampling, >50% of patients had enlarged lymph nodes for <4 months, despite a broad range of differences. However, IgM remained positive for 12-18 months, IgA for 6-9 months and IgE for 4-6 months. IgG avidity remained low for a maximum of 4 months, after which avidity increased despite the persistence of enlarged lymph nodes and a positive IgE assay. Detection of IgE appears to be a highly specific test for confirming the acute nature of Toxoplasma infections that have been detected by other sensitive methods.

Neuroborreliosis in an HIV-1 positive patient.

Simultaneous co-infections of Borrelia burgdorferi sensu lato and HIV-1 are rare events, with only six published cases. A case of acute neuroborreliosis with facial palsy, meningoradiculitis (Bannwarth's syndrome) in an HIV-1 positive individual is described. Diagnosis was confirmed by Western immunoblot analysis of serum and CSF and by proof of intrathecal production of antibodies against B. garinii. The patient was successfully treated with cefotaxime. In all published HIV+ cases, the course of borreliosis did not differ from that of the HIV negative population and the prognosis in properly treated patients was good.

Long-term analysis of the resistance development in HIV-1 positive patients treated with protease and reverse transcriptase inhibitors: correlation of the genotype and disease progression.

In this study, 27 HIV-1-positive patients on long-term highly active antiretroviral therapy (HAART) in the Czech Republic were followed for a period of up to 7 years. Variability of the HIV-1 protease (PR) sequence common in the Czech Republic was observed. Under the pressure of inhibitors of protease (PRIs) and reverse transcriptase (RTIs) mutations in PR were detected. Development of resistance to PRIs was followed by a decrease in CD4 count and increase in viral load. The dynamics of viral load closely corresponded to the accumulation of specific primary mutations in PR and RT. Out of 27 patients 18 developed resistance to PRIs and the prolonged therapy led to the accumulation of a higher number of amino acid changes associated with the resistance and, consequently, cross-resistance to several PRIs was observed. These multi-resistant variants of HIV-1 with mutations in PR could not be inhibited sufficiently with PRIs that are currently available in clinical practice. Efficient yet temporary suppression of viral replication was achieved by a lopinavir (LPV) treatment.

[Acute HIV infection]. / Akutní HIV infekce.

Acute HIV infection occurs in 85% of people recently infected with HIV-1 after an incubation period of 2-6 weeks. Diagnosing the acute HIV infection is difficult because the symptoms are non-characteristic and include fever, pharyngitis, and skin rash. Early recognition of HIV infection is, of course, maximally desirable in order to prevent further transmission of the infection and because the early treatment can slow down later progression of the disease.