Study of immunological features of immune response in 14 children (aged from 12 days up to 15 years) and of 10 adults who developed COVID‐19 show increased number of activated CD4 and CD8 cells ...expressing DR and higher plasmatic levels of IL‐12 and IL‐1β in adults with COVID‐19, but not in children. In addition, plasmatic levels of CCL5/RANTES are higher in children and adults with COVID‐19, while CXCL9/MIG was only increased in adults. Higher number of activated T cells and expression of IL‐12 and CXCL9 suggest prominent Th1 polarization of immune response against SARS‐CoV2 in infected adults as compared with children.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and ...2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person‐years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval CI: 382–523), 136 in Latin America (95% CI: 85–219), 76 in North America (95% CI: 48–119) and 66 in Europe (95% CI: 57–77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio aHR: 2.43, 95% CI: 1.27–4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73–16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37–1.71). Overall, ICC rates increased with age (>50 years vs. 16–30 years, aHR: 1.57, 95% CI: 1.03–2.40) and lower CD4 cell counts at ART initiation (per 100 cell/μl decrease, aHR: 1.25, 95% CI: 1.15–1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer‐related health inequities.
What's new?
Invasive cervical cancer (ICC) is a significant burden among women living with human immunodeficiency virus (HIV). Little is known, however, about geographical differences in ICC rates in women living with HIV. Here, ICC incidence rates in women who received antiretroviral therapy (ART) were compared across geographic regions. ICC incidence was notably high among women living with HIV in South Africa and Latin America. Five years after ART initiation, ICC incidence remained elevated for women in these two regions, compared with women in Europe and North America. Reduced CD4 cell count and older age at ART initiation were associated with increased ICC risk.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background and Aims
Whether the HCV test‐and‐treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown.
Methods
Prospective study of PLWH in the ICONA network. ...At baseline, PLWH were tested for HCV‐Ab; HCV‐RNA (if HCV‐Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re‐infections were evaluated yearly in HCV‐Ab neg and HCV‐RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models.
Results
Sixteen thousand seven hundred and forty‐three PLWH were included; 27.3% HCV‐Ab positive; of these, 39.3% HCV‐RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36–.65); re‐infections incidence: 1.40/100 PYFU (95% CI: .91–2.04). The risk factor for HCV re‐infection was young age: aIRR 1.85, 95% CI: 1.17–2.95) per 10 years younger. 86.4% of HCV viremic in follow‐up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62–.90), HIV‐RNA >50 copies/mL (aHR .70, 95% CI .56–.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post‐COVID‐19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm
3
(vs. CD4 ≥200/mm
3
aOR .18, 95% CI: .07–.46). 95.5% of DAA‐treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow‐up. HCV‐RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022.
Conclusions
The screening‐and‐treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Nirmatrelvir, in combination with ritonavir, is one of the first orally available antiviral treatment for coronavirus disease 2019 (COVID‐19). Symptomatic pregnant women are at increased ...risk for severe illness and complications that can affect the developing baby. No malformations or lower embryo‐fetal survival have been observed when nirmatrelvir were administered to pregnant rats and rabbits. Safety evaluation of drugs used for treating COVID‐19 also in pregnancy is urgent for public health, then in this study we further investigated nirmatrelvir developmental toxicity using zebrafish as in vivo model.
Material and Methods
Using the standardized Fish Embryo Toxicity (FET) test, we first determined the lethal concentration 50 (LC50), exposing embryos from gastrula stage up to 120 hr post fertilization (hpf) and daily recording lethality. Then, we exposed embryos to five doses comprising the human therapeutic one and up to the LC50 (25 μM). Morphology was evaluated at 72 and 120 hpf.
Results
Nirmatrelvir did not affect survival rate and did not induce morphological defects up to the human therapeutic dose. Exposure at higher doses (2.4× and 3× the human Cmax) however resulted in decreased hatching rate, reduced growth, slower heartbeat with pericardial edema, reduction of eye dimension, absence of the swim bladder and disruption of the anterior–posterior axis, with lack of tail detachment, spinal curvature and straight and smaller head.
Conclusions
Our findings in zebrafish embryos add further information about developmental nirmatrelvir safety. Further studies are needed for pharmacological safety assessment of nirmatrelvir exposure during pregnancy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and ...anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial ...translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort.
We included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale).
We studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0-1.1 mg/L; intermediate 1.2-5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model).
Our data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Auto‐antibodies neutralizing the activity of type I interferons have been recently described in patients infected by SARS‐CoV‐2. They can be present even before the onset of the infection. ...Since type I interferons exert a dichotomous role in the pathogenesis of acute versus chronic HIV infection and auto‐antibodies are often found in untreated and anti‐retroviral treated HIV+ patients, we investigated whether auto‐antibodies anti‐type I interferons are present at high prevalence in those HIV+ patients with concomitant opportunistic infections (OIs).
Methods
The analysis of auto‐antibodies against two types of type I interferons (IFN‐α2 and IFN‐ω) was performed using the ELISA test in 60 patients chronically infected by HIV who showed concomitant infections caused by mycobacterium tuberculosis or nontuberculosis mycobacterium or with active cytomegalovirus infections. Results were compared with those of 283 SARS‐CoV‐2 swab positive patients showing mild to severe pneumonia. A chi‐square (χ2) test or the Wilcoxon–Mann–Whitney test were used to compare the HIV+ patient categorical or continuous variables, respectively.
Results
A high prevalence of auto‐antibodies to type I interferons was found in middle‐aged HIV‐infected patients with concomitant OIs (11.6% vs. 5.3% in COVID‐19 subjects; p < .05). No statistically differences were found for viro/immunological characteristics (CD4 and CD8 cell counts and viral load) between patients with and without type I interferons auto‐antibodies.
Conclusions
This study, which is the first searching auto‐antibodies against type I interferons in HIV‐infected patients, demonstrated that their prevalence was higher than that expected by the age of these patients. Furthermore, it indicated that these auto‐antibodies are nonspecifically increased in critical SARS‐CoV‐2 infection but can be found also in other infections.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives
To assess hepatocellular carcinoma (HCC) survival and to investigate the prognostic role of immunonutritional biomarkers, as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ...ratio (PLR) and prognostic nutritional index (PNI), in a cohort of human immunodeficiency virus (HIV)‐infected patients.
Methods
All HIV‐positive patients diagnosed with HCC at our Department from January 2000 to December 2013 were included. The outcomes were overall survival (OS), recurrence‐free survival (RFS), and liver‐related death (LRD). To examine the role of inflammatory biomarkers on the outcomes, univariate and multivariable Cox regression models were used. Receiver operating characteristic (ROC) curves were implemented to evaluate the prediction role of NLR, PLR, and PNI.
Results
A total of 40 patients (90% males) with a mean age of 48.3 years (SD = 5.6) were recruited. NLR ≥ 2.9 was associated with all causes mortality, as well as, PLR ≥ 126. NLR and PLR were predictors of OS, RFS, and LRD, while PNI did not emerge as a prognostic marker. According to the multivariate analysis, no HCC treatment was the only risk factor associated with risk of death. The areas under the ROC curves were 68.3 (95% confidence interval CI, 54.5‐82.1) for PLR and 66.3 (95% CI, 54.3‐78.2) for NLR at 3 years; similar results were found at 5 years of follow‐up.
Conclusions
Although, if examined singularly, NLR and PLR are prognostic factors for HCC recurrence and survival in HIV‐infected patients, at the multivariate analysis, “no HCC treatment” remains the only independent risk factor associated with fatal outcome.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Coronavirus disease 2019 (COVID-19) pandemic poses a great threat to global public health. The original wild-type strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ...genetically evolved, and several variants of concern (VOC) have emerged. On 26 November 2021, a new variant named Omicron (B.1.1.529) was designated as the fifth VOC, revealing that SARS-CoV-2 has the potential to go beyond the available therapies. The high number of mutations harboured on the spike protein make Omicron highly transmissible, less responsive to several of the currently used drugs, as well as potentially able to escape immune protection elicited by both vaccines and previous infection. We reviewed the latest publication and the most recent available literature on the Omicron variant, enlightening both reasons for concern and high hopes for new therapeutic strategies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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