Cross-sectional study on vaccination coverage in newly diagnosed HIV-infected persons in the Czech Republic.

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.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae co-infections among patients with newly diagnosed syphilis: a single-centre, cross-sectional study.

OBJECTIVES: The aim of the study was to determine the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae co-infections among patients with newly diagnosed syphilis. METHODS: In patients with any stage of newly diagnosed syphilis swabs were performed from urethra, rectum, pharynx and cervix according to the gender and type of sexual intercourse. From these smears standard validated nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae infections were done. RESULTS: From 548 (488 men, 60 women) screened patients co-infection was detected in 15.9% of the cases. The majority of the co-infections (86.2%) were asymptomatic. The overall prevalence of chlamydial infection was 11.1% and 8.8% for gonococcal infections. In men who have sex with men (MSM) the prevalence of co-infections was significantly higher (20.0%) than in heterosexual men and women (4.2%) (p < 0.001). In MSM patients the presence of co-infection was significantly associated with HIV infection (p < 0.001). Among MSM 9.6% of the tests detected infection in anorectal site, while prevalence in urethral (2.8%) and pharyngeal (2.4%) localization was significantly lower. In heterosexual patients prevalence was less than 2.0% in all anatomic sites. CONCLUSIONS: The implementation of screening tests in case of sexually transmitted infections in patients with newly diagnosed syphilis is an important part in the management of this disease. These results suggest that screening of asymptomatic heterosexual patients leads to detection of minimum co-infections, but in MSM (especially HIV positive) should always be performed at least in anorectal site, where asymptomatic co-infections are common.

Steady increase of lymphogranuloma venereum cases, Czech Republic, 2010 to 2015.

Since the notification of the first case of lymphogranuloma venereum (LGV) in the Czech Republic in 2010, the numbers of LGV cases have steadily increased in the country. In 2015, 40 LGV cases were diagnosed, bringing the total for 2010-2015, to 88 cases. The profile of the most affected group, HIV-positive men who have sex with men with a previous sexually transmitted infection, matches that of those described in LGV outbreaks in western Europe.

Incidence, predisposing factors, and aetiology of infective endocarditis in the Czech Republic.

OBJECTIVES: The aim of this study was to evaluate the incidence and epidemiological characteristics of infective endocarditis (IE) in the Czech Republic. These results represent the first data on the epidemiology of IE from the post-communist countries. METHODS: This was a prospective multi-centre observational study monitoring the occurrence of IE in the catchment areas of 29 hospitals during a 12-month period. The total monitored territory involved a population of 3.9 million people (37.7% of the total Czech population). Patients were included in the study if they had a diagnosis of possible or definite endocarditis according to the modified Duke criteria. RESULTS: One hundred and thirty-four episodes of IE in 132 patients were reported. Thus the crude incidence of IE was 3.4 cases/100,000 inhabitants/y. Vegetations were most frequently found on the aortic and mitral valves. The most frequent agent was Staphylococcus aureus (29.9%). The aetiology remained unexplained in 33.6% of cases, mainly because of previous antibiotic therapy. Surgical intervention during antibiotic therapy was performed in 36 patients (27.5%). Thirty-six patients died during hospitalization (in-hospital mortality rate 27.5%). The most common predisposing cardiac factors were remote cardiac surgery (19.4%) and degenerative valvular changes (11.9%). The most common extracardiac factors were pyogenic infections of skin and soft tissues (13.0%) and chronic haemodialysis (8.2%). CONCLUSIONS: Our results document the changing epidemiological characteristics of IE, namely an increasing incidence of the disease and an increasing role of Staphylococcus aureus as a major pathogen. A shift was evident in predisposing factors for IE: almost 39% of IE episodes were associated with both cardiac and extracardiac modern medical procedures.

[Lymphogranuloma venereum]. / Lymphogranuloma venereum.

Lymphogranuloma venereum is a sexually transmitted disease caused by serovars L1-3 of Chlamydia trachomatis. This infection was originally endemic in tropics and transmitted predominantly by heterosexual contact but since the beginning of the century it spreads in industrialized countries mainly among men having sex with men causing them severe proctitis. In the Czech Republic the first case was diagnosed in 2011. Lymphogranuloma venereum can resemble other forms of anorectal disorders inclusive inflammatory bowel diseases and thus it must be included into differential diagnostic considerations. Definitive diagnosis is based on detection of specific serovars of Chlamydia trachomatis by polymerase chain reaction. In patients with lymphogranuloma venereum it is also necessary to exclude other sexually transmitted diseases, particularly syphilis, HIV and also hepatitis C. The therapy of choice is doxycycline administered for three weeks.

Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy.

OBJECTIVES: Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients who were under follow-up on ART at 1 July 2008 was therefore developed by imputing data on patients with no prior resistance test results, based on the probability of detecting resistance in tested patients with similar profiles. METHODS: Using all resistance test results available, predicted intermediate/high-level resistance to specific drug classes [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] was derived using the Stanford algorithm v5.1.2. Logistic regression models were then employed to estimate predicted probability of resistance to each drug class for given values of current viral load, history of virological failure and previous virological suppression. Based on these predicted probabilities and patients' covariate profiles, estimates of prevalence in 5355 patients with no prior test results were obtained. Overall prevalence of resistance was estimated by pooling these data with those observed in the remaining 1143 tested patients. RESULTS: Prevalence of NRTI, NNRTI and PI resistance was estimated as 43% (95% confidence interval: 39%-46%), 15% (13%-18%) and 25% (22%-28%), respectively. CONCLUSIONS: This method provides estimates for the proportion of treated patients in a cohort who harbour resistance on a given date, which are less likely to be affected by selection bias due to missing resistance data and will allow us to estimate prevalence of resistance to different drug classes at specific timepoints in HIV-infected populations on ART.

Prevalence of human leukocyte antigen HLA-B*57:01 in HIV-infected subjects in the Czech Republic.

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.

[Our experience with maraviroc treatment in HIV positive patients]. / Nase zkusenosti s maravirocem u HIV pozitivních pacientu.

UNLABELLED: BACKGROUND; Although antiretroviral therapy has changed the clinical course of HIV infection, AIDS remains an incurable disease. Virus entry inhibitors, including maraviroc as the only registered representative of the class, represent a newly emerged group of anti-retrovirals with novel mechanism of action. The primary endpoint is to evaluate the clinical efficacy parameter of maraviroc by measuring viral load at the end of the 4 week treatment period. The secondary endpoint is to evaluate the effectiveness of the drug by monitoring the changes of the viral load values and CD4+ cell counts during the period of 125 weeks. Drug safety was also assessed. METHODS AND RESULTS: Data of 23 subjects were collected, 21 patients were from the Czech Republic and 2 patients from France. Decrease in viral load in the 4th, 24th and 48th week was more than two orders of magnitude (-2.136; -2.448; -2.452 log10 copies/ml). The CD4+ cell count increased (71.71, 143.00, 196.43 cells/mm3). Drug safety was assessed by monitoring the frequency of adverse effects. The data obtained were compared with the III. phase of clinical trials. CONCLUSIONS: Our experience with maraviroc was positive. Maraviroc proved to be an effective antiretroviral agent for a combination therapy of HIV infection.

[Exogenous Cushing's syndrome as a serious side-effect of therapy with ritonavir an inhaled fluticasone]. / Exogenni Gushinguv syndrom jako zavazny nezadouci ucinek lecby ritonavirem a inhalacnim flutikazonem.

Inhalation of fluticasone is usually devoid of systemic side-effects. The authors describe a case of a young HIV positive woman treated concomitantly with fluticasone and inhibitors of HIV protease ritonavir and lopinavir in which developed a serious endocrine side-effect - an iatrogenic Cushing's syndrome. Plasma concentration of cortisol < 5.5 nmol/l was very low (norm 250-650 nmol/l) and plasmatic ACTH was even not detectable. The administration of fluticasone and both inhibitors of HIV protease was stopped and substitution therapy with decreasing dose of hydrocortisone was initiated. Twenty weeks later resolved both clinical and laboratory symptoms of Cushing's syndrome, and the substitution therapy with hydrocortisone was terminated. Two years later became the patient pregnant and gave birth to a healthy child.

The characteristics of HIV-positive patients with mild/asymptomatic and moderate/severe course of COVID-19 disease-A report from Central and Eastern Europe.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Bilateral Holmes-Adie syndrome as an early manifestation of the HIV neuropathy.

A 38-year-old HIV-1 infected woman affected with bilateral tonic pupils. Ophthalmologic examination confirmed Holmes-Adie syndrome (HAS), and peripheral distal polyneuropathy, orthostatic hypotension and leg hyperhidrosis were detected on further workup. The HAS can be either idiopathic or associated with neuropathy of various etiology (autoimmune, paraneoplastic and infectious). In our patient, the pupillotonia was the first and early symptom of hitherto unrecognized HIV neuropathy. HAS has been previously observed in association with syphilis, Lyme borreliosis, herpes simplex and parvovirus B19 infection. Our case is the first report of HAS in a case of HIV infection.

[Two types of CMV ocular complications in patients with HIV infection]. / Dva typy cytomegalovirového postizení oka u pacientu s HIV infekcí.

CMV retinitis is the most serious ocular complication of AIDS. Introduction of the combination antiretroviral therapy markedly reduced the occurrence of CMV retinitis, on the other hand it brought a new ocular complication - CMV uveitis. CMV uveitis is an immunopathological inflammatory reaction associated with the immune reconstitution inflammatory syndrome, which is a side effect of successfully initiated cART. These two forms of CMV ocular complications differ in pathogenesis, symptomatology and therapy. The CMV retinitis is treated with anti-CMV virostatics whereas the therapy of CMV uveitis is based on attenuation of the inflammatory reaction by administration of corticosteroids. The optimal prevention of both complications is an early initiation of cART before the CD4+ T lymphocytes drop below 200/microl.

[HIV retinopathy]. / HIV retinopatie.

HIV retinopathy is an ocular affection occurring especially in HIV positive patients with deep immunodeficiency. Because of benign character the HIV retinopathy does not require any specific therapy, but it must be carefully distinguished from other ocular diseases, which can seriously damage sight, e.g. CMV retinitis. The presence of HIV retinopathy can also be a symptom of progression of HIV infection and should be perceived as a signal for considering the initiation of antiretroviral therapy in treatment naive patients.

[Proposals for guidelines for vaccination of adults infected with HIV-1 in the Czech Republic]. / Návrh doporuceného postupu ockování u dospelých osob infikovaných virem HIV-1.

HIV positive patients are in a higher risk of many infections, including the preventable ones. The vaccination is thus a very important part of health-care offered to those patients. Effectiveness of vaccination correlates strongly with the actual immunological status. Vaccination is safe, including some live vaccines, in persons with CD4+ T cells > 500/ml. In patients with CD4+ T cells > 200/ml the efficacy of vaccination is uncertain and live vaccines are strictly contraindicated. A good knowledge of all aspects of vaccination and HIV-infection is necessary, hence we recommend that vaccination of all HIV-positive persons should be realized exclusively by experts in specialized AIDS centers. In the following text we present the proposals for guidelines for vaccination of adult patients infected with HIV-1.

Expression of TIM-3 on Plasmacytoid Dendritic Cells as a Predictive Biomarker of Decline in HIV-1 RNA Level during ART.

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.

Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen.

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.

Short-term clinical disease progression in HIV-1-positive patients taking combination antiretroviral therapy: the EuroSIDA risk-score.

OBJECTIVES: To derive and validate a clinically applicable prognostic score for predicting short-term disease progression in HIV-infected patients taking combination antiretroviral therapy (cART). DESIGN AND METHODS: Poisson regression was used to identify prognostic markers for new AIDS/death in patients taking cART. A score was derived for 4169 patients from EuroSIDA and validated on 5150 patients from the Swiss HIV Cohort Study (SHCS). RESULTS: In EuroSIDA, 658 events occurred during 22 321 person-years of follow-up: an incidence rate of 3.0/100 person-years of follow-up [95% confidence interval (CI), 2.7-3.3]. Current levels of viral load, CD4 cell count, CD4 cell slope, anaemia, and body mass index all independently predicted new AIDS/death, as did age, exposure group, a prior AIDS diagnosis, prior antiretroviral treatment and stopping all antiretroviral drugs. The EuroSIDA risk-score was divided into four strata; a patient in the lowest strata would have predicted chance of new AIDS/death of 1 in 801, 1 in 401 and 1 in 201 within the next 3, 6 or 12 months, respectively. The corresponding figures for the highest strata were 1 in 17, 1 in 9 and 1 in 5, respectively. A single-unit increase in the risk-score was associated with a 2.70 times higher incidence of clinical progression (95% CI, 2.56-2.84) in EuroSIDA and 2.88 (95% CI, 2.75-3.02) in SHCS. CONCLUSIONS: A clinically relevant prognostic score was derived in EuroSIDA and validated within the SHCS, with good agreement. The EuroSIDA risk-score will be made available publicly via an interface that will perform all calculations for the individual.

Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection.

The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral load measured 6 months prior to starting cART was included in the analyses. Anemia was defined as mild (

[Guidelines for antiretroviral therapy of human immunodeficiency virus (HIV)-infected subjects in the Czech Republic]. / Komplexní postup antiretrovirové lécby osob infikovaných virem lidské imunodeficience (HIV) v Ceské republice.

HIV infection remains an incurable disease because of the impossibility to eradicate the HIV from the organism. However, the combination antiretroviral therapy (cART) is able to efficiently limit HIV replication and slow down progression of immunodeficiency and thus prolong and improve the quality of HIV+ patients? lives. In HIV(+) pregnant women, the antiretroviral therapy substantially reduces the risk of vertical transmission of the infection. According to present knowledge, the cART is indicated mainly in symptomatic patients with stage B or C diseases and for vertical transmission and postexposure prophylaxis; less clear is the indication of cART for treating acute HIV infection and in asymptomatic patients. Various guidelines for the use of antiretroviral agents issued worldwide, e.g. in the USA, Europe or by the WHO, are not completely identical. The authors present a draft of recommendations for the use of antiretroviral agents in the Czech Republic based on the above-mentioned guidelines as well as on their own experience with taking care of HIV/AIDS patients.

[Prophylaxis of the vertical transmission of the human immunodeficiency virus (HIV) in the Czech Republic]. / Profylaxe vertikálního prenosu viru lidské imunodeficience (HIV) v Ceské republice.

GOAL: To assess the efficacy of prophylactic measures intended to reduce vertical transmission of HIV infection and to evaluate the predictive value of demographic, immunological and virological factors for determination of the risk of HIV transmission to fetus and neonate. METHODS: 56 pregnancies of 53 HIV-positive women were included in this retrospective study. The women have been in the care of the AIDS Centre of the Dpt. of Infectious Diseases, University Hospital Na Bulovce over the past 15 years. Cellular immunity tests and HIV RNA viral load in all subjects were regularly determined. In line with our present knowledge and the patients compliance, we introduced prophylactic measures, which included the administration of antiretroviral agents, delivery by Caesarean section and breast-feeding avoidance. 58 children were born from these pregnancies and repeated blood tests were performed to detect the presence or absence of HIV RNA. RESULTS: 58 infants were born from 56 pregnancies-and 3 of them (5.17%) were infected with HIV. In two mothers, we diagnosed HIV positivity few hours before delivery; another woman was diagnosed early, however, the failure of treatment was due to her insufficient compliance. In addition, premature amniorrhoea was present in two women. Moreover, one of them presented with untreated syphilis. The other 55 children stayed uninfected. In six of them, however, prophylactic measures were not fully followed, mainly because the patients disregarded them. CONCLUSIONS: The study fully confirms the high efficacy of prophylactic measures, which substantially reduce the risk of vertical transmission of HIV infection. Routine blood tests are necessary in all pregnant women by law. The failure of prophylaxis is in most cases due to inadequate compliance with the treatment. However, we cannot rule out the possible resistance to antiretroviral agents.