Meeting the WHO 90% target: antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics.

INTRODUCTION: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. M: ethods Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients' characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. RESULTS: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01-2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08-2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04-2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29-2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01-4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52-5.26), p = 0.001]. CONCLUSIONS: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions.

Expanding HIV-1 subtype B transmission networks among men who have sex with men in Poland.

INTRODUCTION: Reconstruction of HIV transmission links allows to trace the spread and dynamics of infection and guide epidemiological interventions. The aim of this study was to characterize transmission networks among subtype B infected patients from Poland. MATERIAL AND METHODS: Maximum likelihood phylogenenetic trees were inferred from 966 HIV-1 subtype B protease/reverse transcriptase sequences from patients followed up in nine Polish HIV centers. Monophyletic clusters were identified using 3% within-cluster distance and 0.9 bootstrap values. Interregional links for the clusters were investigated and time from infection to onward transmission estimated using Bayesian dated MCMC phylogeny. RESULTS: Three hundred twenty one (33.2%) sequences formed 109 clusters, including ten clusters of ≥5 sequences (n = 81, 8.4%). Transmission networks were more common among MSM (234 sequences, 68.6%) compared to other infection routes (injection drug use: 28 (8.2%) and heterosexual transmissions: 59 (17.3%) cases, respectively [OR:3.5 (95%CI:2.6-4.6),p<0.001]. Frequency of clustering increased from 26.92% in 2009 to 50.6% in 2014 [OR:1.18 (95%CI:1.06-1.31),p = 0.0026; slope +2.8%/year] with median time to onward transmission within clusters of 1.38 (IQR:0.59-2.52) years. In multivariate models clustering was associated with both MSM transmission route [OR:2.24 (95%CI:1.38-3.65),p<0.001] and asymptomatic stage of HIV infection [OR:1.93 (95%CI:1.4-2.64),p<0.0001]. Additionally, interregional networks were linked to MSM transmissions [OR:4.7 (95%CI:2.55-8.96),p<0.001]. CONCLUSIONS: Reconstruction of the HIV-1 subtype B transmission patterns reveals increasing degree of clustering and existence of interregional networks among Polish MSM. Dated phylogeny confirms the association between onward transmission and recent infections. High transmission dynamics among Polish MSM emphasizes the necessity for active testing and early treatment in this group.

Transmitted HIV drug resistance in antiretroviral-treatment-naive patients from Poland differs by transmission category and subtype.

OBJECTIVES: The surveillance of HIV-transmitted drug resistance mutations (t-DRMs), including temporal trends across subtypes and exposure groups, remains a priority in the current management of the epidemic worldwide. METHODS: A cross-sectional analysis of 833 treatment-naive patients from 9 of 17 Polish HIV treatment centres. Partial pol sequences were used to analyse drug resistance with a general time reversible (GTR)-based maximum likelihood algorithm used for cluster/pair identification. Mutation frequencies and temporal trends were investigated. RESULTS: t-DRMs were observed in 9% of cases (5.8% for NRTI, 1.2% NNRTI and 2.0% PI mutations) and were more common among heterosexually infected (HET) individuals (13.4%) compared with MSM (8.3%, P = 0.03) or injection drug users (IDUs; 2.9%, P = 0.001) and in MSM compared with IDUs (P = 0.046). t-DRMs were more frequent in cases infected with the non-B variant (21.6%) compared with subtype B (6.6%, P < 0.001). With subtype B a higher mutation frequency was found in MSM compared with non-MSM cases (8.3% versus 1.8% for IDU + HET, P = 0.038), while non-B variants were associated with heterosexual exposure (30.4% for HET versus 4.8% for MSM, P = 0.019; versus 0 for IDU, P = 0.016). Trends in t-DRM frequencies were stable over time except for a decrease in NNRTI t-DRMs among MSM (P = 0.0662) and an NRTI t-DRM decrease in HET individuals (P = 0.077). With subtype B a higher frequency of sequence pairs/clusters in MSM (50.4%) was found compared with HET (P < 0.001) and IDUs (P = 0.015). CONCLUSIONS: Despite stable trends over time, patterns of t-DRMs differed notably between transmission categories and subtypes: subtype B was associated with MSM transmission and clustering while in non-B clades t-DRMs were more common and were associated with heterosexual infections.

Time trends in HIV-1 transmitted drug resistance mutation frequency in Poland.

INTRODUCTION: In Poland, the HIV epidemic has shifted recently from being predominantly related to injection drug use (IDU) to being driven by transmissions among men-who-have-sex-with-men (MSM). The number of new HIV cases has increased in the recent years, while no current data on the transmitted drug resistance associated mutations (tDRM) frequency trend over time are available from 2010. In this study, we analyze the temporal trends in the spread of tDRM from 2008 to 2013. MATERIALS AND METHODS: Partial pol sequences from 833 antiretroviral treatment-naive individuals of European descent (Polish origin) linked to care in 9 of 17 Polish HIV treatment centres were analyzed. Drug resistance interpretation was performed according to WHO surveillance recommendations, subtyping with REGA genotyping 2.0 tool. Time trends were examined for the frequency of t-DRM across subtypes and transmission groups using logistic regression (R statistical platform, v. 3.1.0). RESULTS: Frequency of tDRM proved stable over time, with mutation frequency change from 11.3% in 2008 to 8.3% in 2013 [OR: 0.91 (95% CI 0.80-1,05), p=0.202] (Figure 1a). Also, no significant differences over time were noted for the subtype B (decrease from 8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.79-1.11), p=0.45] and across non-B variants [change from 22.6% 2008 to 23.1% in 2013, OR: 0.94 (95% CI 0.75-1.19), p=0.62]. When patient groups were stratified according to transmission route, in MSM there was a trend for a NNRTI t-DRM decrease (from 6.8% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34-1.02), p=0.0655, slope -0.74%/year) (Figure 1b), related to the subtype B infected MSM (decrease from 7% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34-1.03), p=0.0662, slope -0.75%/year). Overall tDRM frequency decrease was also noted for the heterosexually infected patients [from 17.6% 2008 to 10.3% in 2013, OR: 0.83 (95% CI 0.67-1.02, p=0.077, slope -2.041%/year)] but did not associate with drug class (Figure 1c). In IDUs, the trends in t-DRM frequency were not significant over time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24 (95% CI 0.73-2.26), p=0.4)]. CONCLUSIONS: The frequency of t-DRM in Poland is generally stable over time. Decrease in the overall tDRM frequency in heterosexual infected cases and NNRTI resistance in subtype B infected MSM may be related to the higher treatment efficacy of current cART.

Role of IL-6 and neopterin in the pathogenesis of herpetic encephalitis.

Herpetic encephalitis (HSE) is one of the most severe infection of the central nervous system (CNS), connected with high mortality rate, even when appropriate therapy has been introduced. Better understanding of pathomechanisms responsible for neuronal injury during the course of the disease can be useful in the assessment of the risk of the occurrence of severe complications, as well as in potential introduction of additional therapeutic methods. The purpose of this study is to assess the correlation between concentration of neopterin and IL-6 in the CSF and serum, and the course of HSE. In this study, 36 patients with HSE were investigated, and the control group consisted of 32 patients in whom the infection of the CNS was excluded. We observed significantly higher concentration of neopterin and IL-6 in the CSF of patients with HSV as compared with the control group. Neopterin and IL-6 levels in the CSF correlated with the course of HSE. Higher values were connected with the risk of respiratory failure, development of permanent neurologic complications and patient death. Negative correlations between concentration of IL-6 and neopterin and patient condition assessed by Glasgow Coma Scale (GCS) were observed. Neopterin with high sensitivity and specificity allowed to predict the risk of death or severe neurological complications. Increased concentration of neopterin and IL-6 in the CSF and serum revealed reciprocal positive correlation. Assessment of the concentration of IL-6 and neopterin in the serum was not useful to predict the course of HSE.

[A case of Salmonella paratyphi A infection in Poland]. / Przypadek zawleczenia paraduru typu A do Polski.

Paratyphoid fever is an acute infection caused by Salmonella paratyphi A, B or C. The disease is transmitted from person to person by fecal-oral way. Typical for typhoid fever are splenomegaly, bradycardia, fever, constipation or mild diarrhoea oftten associated with abdominal tenderness. We present the case of patient who was infected by Salmonella paratyphi C while his travelling in Asia.

Morphological changes of the upper gastrointestinal tract mucosa and Helicobacter pylori infection in HIV-positive patients with severe immunodeficiency and symptoms of dyspepsia.

BACKGROUND: HIV infection causes progressive immune defense system dysfunction, including the gastrointestinal (GI) tract. The aim of the study was to evaluate the morphological changes in the upper-GI tract mucosa in HIV-infected patients in relation to the degree of immunodeficiency, presence of H. pylori, fungal colonization, and antiretroviral treatment (HAART). MATERIAL/METHODS: One hundred forty-six patients (94 HIV positive, 52 HIV negative) with dyspeptic symptoms were evaluated by upper GI endoscopy and biopsy. The HIV-infected were divided into two groups: 47 patients with CD4+ count >200/mm(3) and 47 with severe immunodeficiency (CD4+ count <200/mm(3)); 42 of the total patients were treated with HAART. Gastric biopsies for histopathology and urease test, esophageal swabs, and gastric aspirates for mycological evaluation were taken. RESULTS: The HIV-infected patients with severe immunodeficiency had a lower prevalence of H. pylori infection and active chronic gastritis in the gastric antrum compared with the other HIV-infected patients and controls (H. pylori in 40%, 72%, and 69%, respectively; p<0.05). Mycotic esophagitis and mycotic colonization of the stomach were more frequent in patients with severe immunodeficiency. The prevalence of gastric mucosa changes was not different between the patients treated and not treated with HAART; H. pylori infection was less frequent in HIV-infected patients treated with HAART (p<0.05). CONCLUSIONS: In severely immunodeficient patients with dyspeptic symptoms, the prevalence of H. pylori and active chronic gastritis in the gastric antrum is much lower than in HIV-negative patients. H. pylori infection is less frequent in patients treated with HAART.

[Outbreak of Lyme borreliosis with joint manifestation--case report]. / Borelioza z Lyme z zajeciem stawów--opis przypadku.

Lyme borreliosis is caused by the spirochete Borrelia burgdorferi, which is transmitted into the human body by ticks. The clinical symptoms are associated with skin, joints, heart and nervous system. Four groups of antibiotics are used in Lyme borreliosis treatment: penicillins, cephalosporins, tetracyclines and macrolides. We present the case of Lyme borreliosis with outbreak joint manifestation.

[Whooping cough in a previously vaccinated patient--case report]. / Zachorowanie na krztusiec u osoby uprzednio szczepionej--opis przypadku.

Pertussis is an acute contagious human disease caused by gram-negative Coccobacilli Bordetella pertussis. Numerous factors and toxins produced by Bordetella pertussis play important role in pathogenicity of the disease. Typical illness has three clinical stages: catarrhal, paroxysmal and convalescent. In therapy erythromycin is the antibiotic of choice. We present a case of pertussis in a seventeen year old, previously vaccinated patient.

[Studies on relationship between immunodeficiency in HIV-infected people and condition of upper gastrointestinal tract mucosa, prevalence of mycosis and Helicobacter pylori infection]. / Badania nad zaleznoscia uposledzenia odpornosci u osób zakazonych HIV a stanem blony sluzowej górnego odcinka przewodu pokarmowego, wystepowaniem grzybicy i infekcji Helicobacter pylori.

HIV infection leads to progressive deterioration of immunity. Upper gastrointestinal symptoms are often reported in patients with this infection. The aim of the study was to evaluate morphological changes in upper gastrointestinal tract mucosa and prevalence of opportunistic infections and Helicobacter pylori in HIV-infected people in relationship to the degree of immunosupression. We studied 94 HIV-infected patients with dyspeptic symptoms, 47 suffered from severe immunodeficiency expressed by low CD4+ lymphocyte count below 200/ mm3. Control group consisted of 52 non HIV-infected patients. During endoscopy, gastrointestinal tract mucosa was evaluated and biopsy samples were taken from gastric body and antrum for histopathological analysis and rapid urease test. In patients with CD4+ lymphocyte count below 200/mm3, endoscopic examination revealed significantly more frequent esophageal candidiasis (36%); whereas reflux esophagitis (13%) was significantly less often diagnosed in comparison to the rest of the patients. Duodenitis and duodenal erosions were also less frequent in them. Prevalence of Helicobacter pylori infection in gastric antrum was significantly lower in HIV-infected patients with severe immunodeficiency (40%) in comparison to the rest of the patients (72%) and control group (69%). Chronic active gastritis of the antral mucosa was less frequent in HIV-infected patients with CD4+ lymphocyte count below 200/mm3.

[Diagnostic problems in the course of varicella-zoster virus reactivation leading to meningitis and hepatitis--case report]. / Trudnosci diagnostyczne w przebiegu reaktywacji zakazenia wirusem ospy wietrznej i pólpasca pod postacia zapalenia opon mózgowo-rdzeniowych z towarzyszacym zapaleniem watroby--opis przypadku.

Reactivation of varicella-zoster virus (VZV) usually leads to developing of characteristic skin lesions with dermatomal distribution. In very rare cases typical clinical picture can be absent, which impairs diagnostic procedure. Atypical case of young non HIV infected man was described. Clinical picture of meningitis and hepatitis due to VZV reactivation without typical skin eruptions resulted in diagnostic problems and required differentiation with proliterative process. Essential role of serologic testing in such cases was emphasized.