Effects of Pegylated Interferon Alpha and Ribavirin (pegIFN-α/RBV) Therapeutic Approach on Regulatory T Cells in HCV-Monoinfected and HCV/HIV-Coinfected Patients.

Approximately 25% of HIV-infected patients are co-infected with HCV. Notably, the burden of HCV infection (e.g., viral persistence, viral load, or HCV-related liver symptoms) is more pronounced in the presence of HIV co-infection. However, to date, the underlying immune mechanisms accounting for accelerated disease progression in HIV/HCV-coinfected individuals have not been described in sufficient detail. We hypothesized that regulatory T cells (Treg) bearing potent immunosuppressive capacities could not only play a substantial role in the pathogenesis of HCV/HIV coinfection but also modulate the response to the standard anti-viral therapy. MATERIALS AND METHODS: To this end, we studied alterations in frequencies of Treg cells in correlation with other Treg-related and virus-related parameters in both HCV and HCV/HIV-infected patients subjected to standard pegIFN-α/RBV therapy. RESULTS: Notably, we found that pegIFN-α/RBV therapy significantly increased levels of Treg cells in HCV-infected but not in HIV/HCV-coinfected individuals. Furthermore, HIV/HCV-coinfection was demonstrated to inhibit expansion of regulatory T cells during anti-viral treatment; thus, it might probably be responsible for viral persistence and HCV-related liver damage. CONCLUSIONS: Therapy with pegIFN-α/RBV demonstrated a significant effect on regulatory T cells in the course of HIV and/or HCV infection indicating a crucial role in the anti-viral immune response.

High prevalence of anti-HEV antibodies among patients with immunosuppression and hepatic disorders in eastern Poland.

INTRODUCTION: The incidence of hepatitis E virus (HEV) infections in Poland is largely unknown. This study aimed to describe seroprevalence of markers of HEV infection among patients with immunodeficiency of diverse etiology and patients with advanced chronic liver diseases. MATERIAL AND METHODS: Four hundred fifty patients were enrolled; among them, 180 persons were solid organ transplant recipients, 90 patients were HIV-infected and 180 persons had confirmed liver cirrhosis of different etiology. Serum anti-HEV-IgG, IgM antibodies and HEV-antigen were detected by ELISA (Wantai, China). RESULTS: In the group of transplant recipients, serum anti-HEV-IgG antibodies were detected in 40.6%, IgM in 1.1% and HEV-Ag in 2.8% of subjects. In the HIV-infected population 37.7% had anti-HEV-IgG, 1.1% had anti-HEV-IgM and none had HEV-Ag. Among patients with advanced chronic liver diseases the highest prevalence of anti-HEV-IgG was recorded in alcohol-related liver cirrhosis (52.1%) (p = 0.049). In the population of all liver cirrhotics anti-HEV-IgG seroprevalence was 48.3%, anti-HEV-IgM seroprevalence was 5.0% and HEV-Ag seroprevalence was 1.7%. Older age and male gender were significant risk factors associated with increased anti-HEV-IgG prevalence, p = 0.0004 and p = 0.02, respectively. CONCLUSIONS: In this large cohort a high seroprevalence of anti-HEV-IgG was detected in comparison to other European countries, with the highest rates in patients with alcoholic liver disease and in transplant recipients.

Improving the evidence for indicator condition guided HIV testing in Europe: Results from the HIDES II Study - 2012 - 2015.

BACKGROUND: It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. METHODS: Individuals aged 18-65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. RESULTS: Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5-3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. CONCLUSION: The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.

Uptake of tenofovir-based antiretroviral therapy among HIV-HBV-coinfected patients in the EuroSIDA study.

BACKGROUND: According to guidelines all HIV-HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV-HBV patients in the EuroSIDA study. METHODS: All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events. RESULTS: 953 HIV-HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4+ T-cell count <350 cells/mm3 decreased from 85% to 52% in the periods 2002-2006 to 2007-2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events (n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir. CONCLUSIONS: Although use of tenofovir-based cART among HIV-HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.

Metabolic syndrome in HIV infected adults in Poland.

BACKGROUND: Metabolic syndrome (MS) is usually diagnosed based on the presence of abdominal obesity, elevated blood pres-sure (BP), elevated fasting plasma glucose, high serum triglycerides (TG), and low high-density lipoprotein (HDL) cholesterol levels. Whether HIV is associated with a higher prevalence of MS than in the general population remains unclear. AIM: The aim of the study was to determine the incidence of MS in the population of HIV-infected adults and its association with clinical, virological, and biochemical features. METHODS: Two hundred and seventy HIV-infected Caucasian adult patients were enrolled in the study and evaluated based on clinical records in the years 2013-2015. RESULTS: Metabolic syndrome was diagnosed in 60 of 270 (22%) patients, 47 (24%) males and 13 (17%) females, mostly (72%) aged above 40 years. The percentage of patients with diagnosed MS in specific age groups in comparison to the general Polish population for females aged < 40 years was 7% vs. 4%, and males in the same age - 18% vs. 9%, for females aged 40-59 years - 47% vs. 24.4%, and males - 33% vs. 28.3%. Particular components of MS in the MS population were found as follows: body mass index > 30 kg/m2 in 29%, waist circumference exceeding 94 cm in men and 80 cm in woman - 87.5%, TG ≥ 150 mg/dL - 82%, HDL cholesterol < 40/50 mg/dL (males/females) - 42%, systolic/diastolic BP ≥ 130 mmHg/≥ 85 mmHg - 83%, and fasting glucose > 100 mg/dL - 42%. In stepwise multivariate logistic regression analysis, age (odds ratio [OR] 1.052, 95% con-fidence interval [CI] 1.018-1.088, p = 0.003) and nadir CD4 < 350 cells/mm3 (OR 3.576, 95% CI 1.035-12.355, p = 0.04) were associated with MS. Patients with MS compared with those without this disorder had low, intermediate, high, and very high cardiovascular risk in 10% vs. 23%, 73% vs. 70%, 7% vs. 5%, and 10% vs. 2%, respectively (p = 0.006). CONCLUSIONS: Prevalence of MS in the HIV-infected population is higher than in the general Polish population. Age and low nadir CD4 were found to be associated with MS.

[guidelines for HIV testing in Poland].

Including HIV disease in the differential diagnosis is the responsibility of the treating physician. Unfortunately, despite 35 years passed from the description of the first cases of Acquired Immune Deficiency Syndrome, AIDS testing for HIV is offered sporadically in Poland. The aim of this paper is to present the current recommendations for HIV testing.

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.

Hypertension, dyslipidaemia, and cardiovascular risk in HIV-infected adults in Poland.

BACKGROUND: The prevalence of cardiovascular diseases (CVD) in HIV-infected patients increases with aging and duration of the disease. Hypertension, high cholesterol level obesity, diabetes, tobacco exposure, and use of alcohol are among the traditional risk factors that contribute to CVD. AIM: The aim of the study was to determinate the incidence of hypertension, lipid disturbances, and CVD risk in dependence on clinical, viral, and biochemical factors. METHODS: A total of 417 HIV-infected Caucasian adult patients from the four clinical centres in Poland were enrolled and analysed on the basis of available medical data from the years 2013-2015. RESULTS: Hypertension was diagnosed in 28% of all patients and in the age ranges: < 40 years, 41-60 years and > 60 years in 18%, 43%, and 53%, respectively. The percentage of optimal, normal, and high normal blood pressure was: 28%, 14%, and 30%, respectively. Hypertension grade 1, 2, and 3 was observed in 58%, 35%, and 7% of patients, respectively. Factors associated with hypertension were: increasing age, male sex, increased body mass index, hypercholesterolaemia, hypo-high density lipoprotein (HDL), hypertriglyceridaemia and duration of HIV infection more than 10 years. Hypercholesterolaemia, suboptimal level of HDL, elevated low-density lipoprotein, and hypertriglyceridaemia were observed in 37%, 20.5%, 31%, and 52%, respectively. Hypertriglyceridaemia was associated with protease inhibitor-based highly active antiretroviral therapy. HCV infection was negatively associated with hypercholesterolaemia. Cigarette smoking was reported in 55% of cases. CONCLUSIONS: Incidence of hypertension in particular age groups of HIV infected people is higher than in the general Polish population. Hypertension is influenced by traditional risk factors and duration of HIV infection but not antiretroviral treatment. HIV/HCV coinfection appears to be protective against hypercholesterolaemia.

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.

Distribution and time trends of HIV-1 variants in Poland: Characteristics of non-B clades and recombinant viruses.

The spread of HIV-1 subtypes varies considerably both worldwide and within Europe, with non-B variants commonly found across various exposure groups. This study aimed to analyse the distribution and temporal trends in HIV-1 subtype variability across Poland. For analysis of the subtype distribution, 1219 partial pol sequences obtained from patients followed up in 9 of 17 Polish HIV treatment centres were used. Subtyping was inferred using the maximum likelihood method; recombination was assessed using the bootscanning and jumping profile hidden Markov model methods. Subtype B dominated in the studied group (n=1059, 86.9%); in 160 (13.1%) sequences, non-B variants were present [A1 (n=63, 5.2%), D (n=43, 3.5%), C (n=22, 1.8%), and F1 (n=2, 0.2%)]. In 25 (2.1%) cases circulating recombinant forms (CRFs) were found. Five A1 variants (0.4%) were unique AB recombinant forms (URF) not previously identified in Poland. Non-B clades were notably more common among females (n=73, 45.6%, p<0.001) and heterosexual individuals (n=103, 66.5%, p<0.001) and less frequent among men who have sex with men (MSM) (n=27, 17.42%, p<0.001). HIV-1 viral load at diagnosis was higher among non-B cases [median: 5.0 (IQR: 4.4-5.6)] vs. [median: 4.8 (IQR: 4.3-5.4) log copies/ml for subtype B (p<0.001)] with a lower CD4(+) lymphocyte count at baseline [median: 248 (IQR: 75-503) for non-B vs. median: 320 (IQR: 125-497) cells/µl for subtype B; p<0.001]. The frequency of the non-B subtypes proved stable from 2008 (11.5%) to 2014 (8.0%) [OR: 0.95 (95% CI: 0.84-1.07), p=0.4], with no temporal differences for exposure groups, gender, age and AIDS. Despite the predominance of subtype B, the variability of HIV in Poland is notable; both CRFs and URFs are present in the analysed population. Non-B variants are associated with heterosexual transmission, more advanced HIV disease and have stable temporal frequencies.

The Spectrum of Malignancies among Adult HIV Cohort in Poland between 1995 and 2012: A Retrospective Analysis of 288 Cases.

THE AIM OF THE STUDY: The aim of the study was to evaluate the spectrum of AIDS-defining malignancies (ADMs) and non-AIDS-defining malignancies (NADMs) in HIV-infected patients in Poland. MATERIAL AND METHODS: A retrospective observational study was conducted among HIV-infected adult patients who developed a malignancy between 1995 and 2012 in a Polish cohort. Malignancies were divided into ADMs and NADMs. Non-AIDS-defining malignancies were further categorised as virus-related (NADMs-VR) and unrelated (NADMs-VUR). Epidemiological data was analysed according to demographic data, medical history, and HIV-related information. Results were analysed by OR, EPITools package parameters and Fisher's exact test. RESULTS: In this study 288 malignancies were discovered. The mean age at diagnosis was 41.25 years (IQR20-81); for ADMs 38.05 years, and for NADMs-VURs 46.42 years; 72.22% were male, 40.28% were co-infected with HCV. The risk behaviours were: 37.85% IDU, 33.33% MSM, and 24.31% heterosexual. Mean CD4+ at the diagnosis was 282 cells/mm(3) (for ADMs 232 and for NADMs-VUR 395). Average duration of HIV infection at diagnosis was 5.69 years. There were 159 (55.2%) ADMs and 129 (44.8%) NADMs, among whom 58 (44.96%) NADMs-VR and 71 (55.04%) NADMs-VUR. The most frequent malignancies were: NHL (n = 76; 26.39%), KS (n = 49; 17.01%), ICC (n = 34; 11.81%), HD (n = 23; 7.99%), lung cancer (n = 18; 6.25%) and HCC (n = 14; 4.86%). The amount of NADMs, NADMs-VURs in particular, is increasing at present. Male gender (OR = 1.889; 95% CI: 1.104-3.233; p = 0.024), advanced age: 50-60 years (OR = 3.022; 95% CI: 1.359-6.720; p = 0.01) and ≥ 60 years (OR = 15.111; 95% CI: 3.122-73.151; p < 0.001), longer duration of HIV-infection and successful HAART (OR = 2.769; 95% CI: 1.675-4.577; p = 0) were independent predictors of NADMs overall, respectively. CONCLUSIONS: In a Polish cohort NHL was the most frequent malignancy among ADMs, whereas HD was the most frequent among NADMs. Increased incidence of NADMs appearing in elderly men with longer duration of HIV-infection and with better virological and immunological control was confirmed. As HIV-infected individuals live longer, better screening strategies, especially for NADMs-VUR, are needed. The spectrum of cancer diagnoses in Poland currently does not appear dissimilar to that observed in other European populations.

Prevalence and Risk Factors of HCV/HIV Co-Infection and HCV Genotype Distribution in North-Eastern Poland.

BACKGROUND: HIV/HCV co-infection predisposes to accelerated liver damage and increased both liver-related and unrelated morbidity and mortality in patients with HIV infection. OBJECTIVES: The aim of this study was to evaluate the prevalence of HCV infection, seropositivity, risk factors and genotype distribution among treated HIV positive patients. Furthermore, the occurrence and causes of deaths were analyzed. PATIENTS AND METHODS: Adult HIV-1 infected patients, with at least one antiHCV result, treated in one of Polish HIV/AIDS reference centers, participated in this cross-sectional study. RESULTS: Four hundred and fifty seven patients with a median age of 38 years (ranged 23 - 72), and predominantly male (76.6%) were enrolled in the study. Anti-HCV antibodies were detected in 325 individuals (71.1%). HCV RNA was detected in 207 of the 233 patients tested (88%). The HCV genotype analysis (n = 193) demonstrated almost equal distribution with slight genotype 1 domination as 37.3%, mainly 1b, followed by genotypes 3 as 32.1% and 4 as 30.6%. No association was found between HCV genotype and route of HIV acquisition. In univariate analysis, higher HCV seropositivity was related to male sex, intravenous drug use (IDU), mode of HIV transmission, history of drug and alcohol abuse and imprisonment. In multivariate analysis, only being injection drug user (P = 0.0001), imprisonment (P = 0.310) and younger age at the HIV diagnosis per each year (P = 0.025) were identified as risk factors for HCV infection. Sixty three deaths were reported; no association was found between HCV seropositivity and death prevalence. CONCLUSIONS: HIV/HCV co-infection is an important medical problem in North-Eastern Poland. A history of incarceration and younger age at HIV diagnosis were additional to IDU risk factors for HCV seropositivity in this cohort.

Influence of HCV and HIV on development of cryoglobulinemia.

Cryoglobulinemic syndrome refers to a systemic inflammatory process that involves small and medium-sized vessels accompanied by multi-organ damage. The aim of the present study was to determine the incidence of cryoglobulinemia among patients infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HCV/HIV co-infection, as well as evaluation of cryoglobulinemia type. The association was evaluated between cryoglobulinemia and clinical symptoms, selected biochemical measures of liver and kidney function, virologic measures, as well as histopathological changes in the liver. One hundred and forty-one patients were enrolled (59 HCV mono-infected, 48 HIV mono-infected, and 34 HCV/HIV co-infected). Cryoglobulinemia was nearly five times less frequent among HIV mono-infected patients (10%) than HCV mono-infected (53%) and HCV/HIV co-infected patients (59%). Cryoglobulinemia was more frequent in patients infected with genotype 1 HCV than genotype 3 (63% vs. 46%, p=0.12). There was a lower incidence of cryoglobulinemia in HIV mono-infected patients treated with antiretroviral drugs (p=0.04). Cryoglobulinemia correlated with ALT activity (p=0.01) and HIV viral load (p<0.001). Symptoms were significantly more frequent among cryoglobulinemic patients than those without cryoglobulinemia (38% vs. 9%, p<0.001). The most common symptoms related to cryoglobulinemia, regardless of cryoglobulinemia type, were fatigue (38%), arthralgia (20%), polineuropathy (18%), and skin lesions (14%). In conclusion, HCV mono-infection and HCV/HIV co-infection, regardless of HCV genotype, are potent stimulators of cryoglobulinemia, with its symptomatic form occurring in about 40% of cases. Effective antiretroviral therapy seems to be protective against cryoglobulinemia development in HIV mono-infected patients.

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.

Glucocorticoid treatment at moderate doses of SIVmac251-infected rhesus macaques decreases the frequency of circulating CD14+CD16++ monocytes but does not alter the tissue virus reservoir.

Subsets of CD16-positive monocytes produce proinflammatory cytokines and expand during chronic infection with the human immunodeficiency virus type 1 (HIV). HIV-infected macrophage in tissues may be long lived and contribute to the establishment and maintenance of the HIV reservoir. We found that the (intermediate) CD14(++)CD16(+) and (nonclassical) CD14(+)CD16(++) monocyte subsets are significantly expanded during infection of Rhesus macaques with pathogenic SIV(mac251) but not during infection of sooty mangabeys with the nonpathogenic isolate SIVSM. In vitro glucocorticoid (GC) treatment of peripheral blood mononuclear cells (PBMCs) from uninfected or SIV(mac251)-infected Rhesus macaques and HIV-infected patients treated or not with antiretroviral therapy (ART) resulted in a significant decrease in the frequency of both CD16-positive monocyte subsets. Short-term in vivo treatment with high doses of GC of chronically SIV(mac251)-infected macaques resulted in a significant decrease in the CD14(+)CD16(++) population and, to a lesser extent, in the CD14(++)CD16(+) monocytes, as well as a significant decrease in the number of macrophages in tissues. Surprisingly, treatment of SIV(mac251)-infected macaques with ART significantly increased the CD14(++)CD16(+) population and the addition of GC resulted in a significant decrease in only the CD14(+)CD16(++) subset. No difference in SIV DNA levels in blood, lymph nodes, gut, and spleen was found between the groups treated with ART or ART plus GC. Thus, it appears that high doses of GC treatment in the absence of ART could affect both CD16-positive populations in vivo. Whether the efficacy of this treatment at higher doses to decrease virus levels outweighs its risks remains to be determined.

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.

The justification for the early introduction of antiretroviral therapy in patients living with HIV.

In the last years the retroviral disease, caused by the human immunodeficiency virus (HIV), turned from an incurable to a chronic disease. This fundamental change happened due to a huge progress in the understanding of the pathogenesis and treatment of this infection. However, one question still remains open: what is the best time to introduce therapy. The CD4 count is the point of reference to start of the treatment in HIV infected patients. Tendency to introduce highly active antiretroviral therapy (HAART) as early as possible has been observed recently. According to the most recent guidelines of the World Health Organization HAART should be started when CD4 reaches < or = 500 cells/microl. The aim of this paper is justification for the early introduction of antiretroviral therapy in patients living with HIV.

The importance of sCD40 and sCD40L concentration in patients with chronic HCV infection and HIV co-infection.

CD40 receptor is activated by ligand CD40L (CD154) which is synthesized in inflammation by NK cells, monocytes and lymphocytes B. TRAF proteins are activated in cells by CD40 stimulation and next they stimulate different enzymatic pathways. High concentrations of CD40L stimulate CD40, and consequently STAT enzyme system inhibits the expression ofnonstructural proteins ofHCV NS3 and NS5A and E2 core in infected human hepatocytes. PURPOSE. The aim of the study was to evaluate the concentration of soluble components of the complex: sCD40 and sCD40L in the serum of patients infected with HCV and HCV/HIV-1 co-infected. The effect ofHCV genotype, HIV and HCV viral load and rs12979860 polymorphism on serum sCD40 and sCD40L was established among the patients. The influence of the number of CD3+, CD4+ and CD8+ on the concentrations of sCD40 and sCD40L was evaluated in the HIV-1 infected group MATERIALS AND METHODS. Serum concentrations of sCD40 and sCD40L were determined using ELISA in 68 HCV infected patients including 39 HCV monoinfected and 29 HCV/HIV-1 co-infected. RESULTS. Serum concentration of sCD40 and sCD40L was significantly higher in HCV and HCV/HIV coinfected patients compared to healthy subjects (25.7 and 23.2 v. 8.5 pg/ml and 12.7 and 7.3 v. 0.79 ng/ml). The concentration of sCD40L in patients with genotype CC rs12979860 was significantly higher compared to patients with Non-CC genotypes (11.8 v. 7.6 ng/ml, p < 0.018). CONCLUSIONS. High levels of sCD40 and sCD40L were detected among patients with chronic HCV and HCV/ HIV-1 infection The high concentration of sCD40L correlates with CC rs12979860 genotype.

Phylogeographic analysis on the travel-related introduction of HIV-1 non-B subtypes to Northern Poland.

Phylodynamic, sequence data based reconstructions for the surveillance of the geographic spatial spread are a powerful tool in molecular epidemiology. In this study region of origin for the set of 57 partial pol sequences derived from the patients the history of travel-related HIV transmission was analyzed using phylogeographic approach. Maximum likelihood trees based on the sets of country-annotated reference sequences were inferred for identified non-B variants. Region of sequence import was assigned using on the highest approximate likelihood ratios. Import of the A1 clades was traced to the Eastern Europe and associated with immigration from this region. Subtype C infections clustered most frequently with sequences of the South African origin while majority of subtype Ds were similar to the European clades. Subtype G sequences clustered with Portuguese lineage, CRF01_AE with Eastern or South-Eastern Asian. Eastern European, Middle African or Western African lineage was assigned for the CFR02_AG. Rare circulating recombinants originated either from Central Africa (CRF11_cpx - Democratic Republic of Congo, CRF13_cpx - Central African Republic, CRF37_cpx - Cameroon) or South America (CRF28_BF and CRF46_BF - Brazil). Import of the HIV-1 non-B variants, including recombinant forms previously rarely found in Poland and Europe is frequent among travelers. Observed founder events result in the heterosexually-driven introduction of the novel HIV-1 variants into the population.

[Delayed HIV disease diagnosis, despite multiple hospitalizations--case report]. / Pózne rozpoznanie choroby retrowirusowej, mimo wielokrotnych hospitalizacji--opis przypadku.

Prevalence of human immunodeficiency virus (HIV) infection remains very low in Poland and is estimated to be 0.2%. The number of people undergoing HIV-testing is low. Only 10% population was ever tested and the HIV morbidity increases yearly in Poland. The percentage of late diagnoses is high and remains so in recent years. The aim of the current paper was to present a case of female patient, the partner intravenous drug user, who was hospitalized several times due to: aseptic meningitis, delivery, thrombocytopenia and was never offered a HIV testing. The disease was diagnosed at the late stage with CD4 count of 39 cells/microl (13%). Diagnosis of the disease at the advanced stage potentially reduces a chance for successful treatment and is associated with worse prognosis. Routine testing for HIV infection should be widely available in any health care facility and be directed in particular to people with specific indicator conditions or risky behaviors.