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.
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.
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.
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.
Peripheral arterial disease (PAD) is a clinical manifestation of atherosclerosis and mainly refers to elderly patients, having a negative impact on their functionality and quality of life. The ...findings of previous studies in HIV-infected patients have shown that cardiovascular risk is higher and PAD occurs more frequently than in the general population. There are also contradictory observations. Much less is known about the ankle-brachial index (ABI) value in asymptomatic HIV-infected patients. The aim of this study was to evaluate the prevalence of PAD and ankle-brachial index abnormalities as well as to determine risk factors related to the disease in a group of Polish HIV-positive patients.
One hundred and eleven young to middle aged HIV-positive subjects and 40 noninfected subjects were enrolled into the study. Resting ABI measurements were performed and cardiovascular risk was analysed as well. Subgroups were created according to the ABI values: low (PAD), borderline, normal, high and altered ABI. Symptomatic PAD was observed in 2 HIV-positive patients, asymptomatic PAD was not diagnosed. The ABI value is lower and more varied, in 22.5% of the study group altered ABI values were found. Six subjects demonstrated borderline ABI, and 15 high ABI, including >1.4. In the control group no low or very high values were reported. A relation between low ABI and cardiovascular family history and between altered ABI and high-density-lipoprotein cholesterol (HDL-C) level was demonstrated.
In young and middle-aged HIV-positive patients, symptomatic PAD prevalence is comparable to that observed in the overall population. Among asymptomatic patients PAD is not reported. The ABI value in HIV-positive patients is more varied compared to the HIV-negative subjects; the altered ABI shows a strong relation with low HDL-C levels and metabolic syndrome.
•Half of the HCV-infected patients showed abnormal evoked potentials before therapy.•Interferon-free therapy positively affects the bioelectrical activity of the brain.•Evoked potentials examination ...may be a useful method of assessing the function of the nervous system.
The aim of this study was to investigate brain bioelectrical activity disturbances in HCV-positive patients before and 24 weeks after interferon-free therapy (DAA), using visual (VEP) and brainstem (BAEP) evoked potentials and advanced magnetic resonance techniques.
11 HCV-infected patients (6 women, 5 men, mean age 51 years old) and 30 healthy controls, sex and age-matched, were studied. Clinical neurological examinations, VEP, BAEP, diffusion tensor imaging (DTI) and perfusion weighted imaging (PWI) were performed.
11 patients achieved a sustained viral response, and liver fibrosis regression in APRI and in elastography were observed. The mean P100 latency was significantly shorter in HCV-patients after therapy compared to the values before treatment (p<0.05). The mean wave BAEP V latency and I–V interpeak latency were significantly longer in the HCV-infected patients before therapy compared to HCV-patients after therapy.
This study confirms that treatment with DAA in patients with chronic HCV infection positively affects the bioelectrical activity of the brain. An increase in the amplitude of EP after treatment indicates an improvement in the activity of the cerebral cortex. EP examination may be a useful method of assessing the function of the nervous system before and after antiviral treatment.
Asymptomatic central nervous system (CNS) involvement occurs in the early stage of the human immunodeficiency virus (HIV) infection. It has been documented that the hepatitis C virus (HCV) can ...replicate in the CNS. The aim of the study was to evaluate early disturbances in cerebral microcirculation using magnetic resonance (MR) perfusion-weighted imaging (PWI) in asymptomatic HIV-1-positive and HCV-positive patients, as well as to assess the correlation between PWI measurements and the clinical data.
Fifty-six patients: 17 HIV-1-positive non-treated, 18 HIV-1-positive treated with combination antiretroviral therapy (cART), 7 HIV-1/HCV-positive non-treated, 14 HCV-positive before antiviral therapy and 18 control subjects were enrolled in the study. PWI was performed with a 1.5T MR unit using dynamic susceptibility contrast (DSC) method. Cerebral blood volume (CBV) measurements relative to cerebellum (rCBV) were evaluated in the posterior cingulated region (PCG), basal ganglia (BG), temporoparietal (TPC) and frontal cortices (FC), as well as in white matter of frontoparietal areas. Correlations of rCBV values with immunologic data and liver histology activity index (HAI) were analyzed.
Significantly lower rCBV values were found in the right TPC and left FC as well as in PCG in HIV-1-positive naïve (p = 0.009; p = 0.020; p = 0.012), HIV-1 cART treated (p = 0.007; p = 0.009; p = 0.033), HIV-1/HCV-positive (p = 0.007; p = 0.027; p = 0.045) and HCV-positive patients (p = 0.010; p = 0.005; p = 0.045) compared to controls. HIV-1-positive cART treated and HIV-1/HCV-positive patients demonstrated lower rCBV values in the right FC (p = 0.009; p = 0.032, respectively) and the left TPC (p = 0.036; p = 0.005, respectively), while HCV-positive subjects revealed lower rCBV values in the left TPC region (p = 0.003). We found significantly elevated rCBV values in BG in HCV-positive patients (p = 0.0002; p<0.0001) compared to controls as well as to all HIV-1-positive subjects. There were no significant correlations of rCBV values and CD4 T cell count or HAI score.
PWI examination enables the assessment of HIV-related as well as HCV-related early cerebral dysfunction in asymptomatic subjects. HCV-infected patients seem to reveal the most pronounced perfusion changes.
Since the end of December 2020, it has been possible to vaccinate against COVID-19. Our aim was to evaluate and compare the effectiveness of the vaccines available at the time of the mass vaccination ...program in Poland and also to look into the most common adverse side effects. Patients’ anti-SARS-CoV-2 antibodies levels were checked before vaccination and after the first and after the second/last dose by the anti-SARS-CoV-2 QuantiVac ELISA (IgG) (EUROIMMUN MedicinischeLabordiagnostica AG; Luebeck; Germany) test. Before each blood collection, all patients filled out a questionnaire regarding experienced side effects. We observed that 100% of patients responded to the vaccinations. After the first dose, convalescents had much higher levels of anti-SARS-CoV-2 antibodies than naive patients, although after the second dose, 61 out of 162 convalescents (37.7%) had lower results than before. The comparison of immunological responses in the convalescents group after the first dose and in the naive group after the second dose showed that convalescents had higher antibody titers, which may suggest the possibility of changing the vaccination schedule for convalescents. The highest antibody titers after both the first and second doses were observed after Moderna shots. Fever was identified as a significant factor regarding higher levels of antibodies after the first and second doses of the vaccine.
AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin(peg IFN/RBV), in treatment-naive hepatitis C virus(HCV) genotype(GT) 1-infected patients.METHODS: In ...this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned(2:1) to daclatasvir vs telaprevir, stratified by IL28 B rs12979860 host genotype(CC vs non-CC), cirrhosis status(compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype(GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus peg IFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus peg IFN/RBV; those without an extended rapid virologic response(e RVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of peg IFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus peg IFN/RBV followed by 12(with e RVR) or 36(no e RVR) wk of peg IFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12(SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia(hemoglobin < 10 g/d L) and rashrelated events, through week 12, were lower with daclatasvir + peg IFN/RBV than with telaprevir + peg IFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5 A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/m L, to investigate any link between NS5 A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups(6.0% and 8.2% in the GT1 b and GT1 a groups, respectively) than in the telaprevir groups(2.2% and 3.0%). Among GT1 binfected patients, daclatasvir plus peg IFN/RBV was noninferior to telaprevir plus peg IFN/RBV for SVR12 85%(228/268) vs 81%(109/134); difference, 4.3%(95%CI:-3.3% to 11.9%). Anemia(hemoglobin < 10 g/d L) was significantly less frequent with daclatasvir than with telaprevir difference,-29.1%(95%CI:-38.8% to-19.4%). Rash-related events were also less common with daclatasvir than with telaprevir, but the difference was not statistically significant. In GT1 ainfected patients, SVR12 was 64.9% with daclatasvir and 69.7% with telaprevir. Among both daclatasvir and telaprevir treatment groups, across GT1b- or GT1a-infected patients, lower response rates were observed in patients with IL28 B non-CC and cirrhosis- factors known to affect response to peg IFN/RBV. Consistent with these observations, a multivariate logistic regression analysis in GT1b-infected patients d e m o n s t ra t e d t h a t S V R 1 2 wa s a s s o c i a t e d w i t h IL28 B host genotype(CC vs non-CC, P = 0.011) and cirrhosis status(absent vs present, P = 0.031). NS5 A polymorphisms associated with daclatasvir resistance(at L28, R30, L31, or Y93) were observed in 17.3% of GT1b-infected patients at baseline; such variants did not appear to be absolute predictors of failure since 72.1% of these patients achieved SVR12 compared with 86.9% without these polymorphisms. Among GT1b-infected patients, treatment was completed by 85.4%(229/268) in the daclatasvir group, and by 85.1%(114/134) in the telaprevir group, and among GT1a-infected patients, by 67.2%(90/134) and 69.7%(46/66), respectively. Discontinuations(of all 3 agents) due to an AE were more frequent with telaprevir than with daclatasvir, whereas discontinuations due to lack of efficacy were more frequent with daclatasvir, due, in part, to differences in futility criteria. CONCLUSION: Daclatasvir plus peg IFN/RBV demonstrated noninferiority to telaprevir plus peg IFN/RBV for SVR12 and was well-tolerated in treatment-naive GT1 binfected patients, supporting the use of daclatasvir with other direct-acting antivirals.
The human genome contains about 8% of endogenous retroviral sequences originated from germ cell infections by exogenous retroviruses during evolution. Most of those sequences are inactive because of ...accumulation of mutations but some of them are still capable to be transcribed and translated. The latter are insertionally polymorphic HERV-K113 and HERV-K115. It has been suggested that their presence and expression was connected with several human diseases. It is also believed that they could interfere with the replication cycle of exogenous retroviruses, including HIV.
Prevalence of endogenous retroviral sequences HERV-K113 and HERV-K115 was determined in the Polish population. The frequencies were found as 11.8% for HERV-K113 and 7.92% for HERV-K115. To verify the hypothesis that the presence of these HERVs sequences could affect susceptibility to HIV infection, comparison of a control group (HIV-negative, not exposed to HIV; n = 303) with HIV-positive patients (n = 470) and exposed but uninfected (EU) individuals (n = 121) was performed. Prevalence of HERV-K113 and HERV-K115 in the EU group was 8.26% and 5.71%, respectively. In the HIV(+) group we detected HERV-K113 sequences in 12.98% of the individuals and HERV-K115 sequences in 7.23% of the individuals. There were no statistically significant differences between groups studied.
The frequency of HERV-K113 and HERV-K115 sequences in Poland were found to be higher than usually shown for European populations. No relation between presence of the HERVs and HIV infection was detected.
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