In our work, we analyzed the role of the CD100/CD72 and PD-1/PD-L1 axes in immune response dysfunction in human immunodeficiency virus (HIV)-1 infection in which high expressions of PD-1 and PD-L1 ...were associated with an immunosuppressive state via limitation of the HIV-1-specific T-cell responses. CD100 was demonstrated to play a relevant role in immune responses in various pathological processes and may be responsible for immune dysregulation during HIV-1 infection. We investigated the function of CD72/CD100, and PD-1/PDL-1 axes on T and B cells in HIV-infected individuals and in healthy individuals. We analyzed the frequencies and fluorescence intensities of these four markers on CD4+, CD8+ T and B cells. Marker expressions were increased during active HIV-1 infection. CD100 frequency on T cells was positively associated with the expression of PD-1 and PD-L1 on T cells from HIV-infected treatment-naïve individuals. In addition, the frequency of CD72-expressing T cells was associated with interferon gamma (IFN-γ) production in HIV-infected treatment-naïve individuals. Our data suggest that the CD72/CD100 and PD-1/PD-L1 axes may jointly participate in dysregulation of immunity during HIV-1 infection and could partially explain the immune systems' hyper-activation and exhaustion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Respiratory syncytial virus: A new era Ruiz-Galiana, J; Cantón, R; De Lucas Ramos, P ...
Revista española de quimioterapia,
04/2024, Letnik:
37, Številka:
2
Journal Article
Odprti dostop
Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and ...rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain.
To evaluate the efficacy and safety of 96 weeks of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) treatment in participants switching from dolutegravir (DTG)-based therapy.
Studies 1489 ...(NCT02607930) and 1490 (NCT02607956) were phase 3 randomized, double-blind, active-controlled, first-line therapy trials in people with HIV-1. After 144 weeks of DTG-based or B/F/TAF treatment, participants could enter a 96-week open-label extension (OLE) of B/F/TAF.
A pooled analysis evaluated viral suppression (HIV-1 RNA <50 copies/ml) and changes in CD4 + cell count at OLE Weeks 48 and 96, treatment-emergent resistance, safety, and tolerability after switch from a DTG-based regimen to B/F/TAF. Outcomes by prior treatment were summarized using descriptive statistics and compared by two-sided Wilcoxon rank sum test.
At OLE Week 96, participants who switched to B/F/TAF ( N = 519) maintained high levels of virologic suppression (99.5 and 99.1% in those switching from DTG/abacavir/lamivudine and DTG+F/TAF, respectively) and CD4 + cell count, with no treatment-emergent resistance to B/F/TAF. Twenty-one participants experienced drug-related adverse events after switching, with diarrhea, weight gain, and headache occurring most commonly. There were no cases of proximal renal tubulopathy, drug-related Grade 4 adverse events, or serious adverse events. Two participants discontinued B/F/TAF due to treatment-related adverse events. Participants who switched from DTG/abacavir/lamivudine experienced statistically significant greater weight gain than those who switched from DTG+F/TAF; however, median weight change from the blinded phase baseline to OLE Week 96 was numerically similar across treatment groups.
This medium-term analysis demonstrates the safety and efficacy of switching to B/F/TAF from a DTG-containing regimen in people with HIV-1.
This study examines the relationship between regulatory B (Breg) and T (Treg) compartments, which play crucial roles in the maintenance of immune homeostasis in the context of HIV. Using flow ...cytometry, the phenotypes of different Breg and Treg subsets from HIV-infected and healthy individuals were analyzed, along with the suppressive capacity of Breg. Peripheral blood samples of thirteen HIV+ treatment-naïve individuals, fourteen treated-HIV+ individuals with undetectable viral load and twelve healthy individuals were analyzed. The absolute counts of Breg and Treg subsets were decreased in HIV+ treatment-naïve individuals in comparison to treated-HIV+ and healthy individuals. Interestingly, correlations between Breg subsets (CD24hiCD27+ and PD-L1+ B cells) and IL-10-producing Breg observed in healthy individuals were lost in HIV+ treatment-naïve individuals. However, a correlation between frequencies of CD24hiCD38hi or TIM-1+-Breg subsets and Treg was observed in HIV+ treatment-naïve individuals and not in healthy individuals. Therefore, we hypothesized that various Breg subsets might have different functions during B and T-cell homeostasis during HIV-1 infection. In parallel, stimulated Breg from HIV-infected treatment-naïve individuals presented a decreased ability to suppress CD4+ T-cell proliferation in comparison to the stimulated Breg from treated-HIV+ or healthy individuals. We demonstrate a dysregulation between Breg and Treg subsets in HIV-infected individuals, which might participate in the hyper-activation and exhaustion of the immune system that occurs in such patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Introduction
The main challenge in the treatment of Clostridioides difficile infection (CDI) is to reduce recurrence rates. Fidaxomicin improves the recurrence rate of CDI compared with ...vancomycin. Extended-pulsed dosing of fidaxomicin was associated with lower recurrence rates in one clinical trial but has never been directly compared with conventional fidaxomicin dosing.
Methods
To compare the recurrence rate of fidaxomicin conventional dosing (FCD) and fidaxomicin in extended-pulsed dosing (FEPD) in conditions of clinical practice at a single institution. We performed propensity score matching taking the variables age, severity and previous episode as confounders to evaluate patients with a similar recurrence risk.
Results
In total, 254 episodes of CDI treated with fidaxomicin were evaluated: 170 (66.9%) received FCD, and 84 (33.1%) received FEPD. More patients who received FCD were hospitalized for CDI, had severe CDI and had a diagnosis based on toxin detection. In contrast, the proportion of patients receiving proton pump inhibitors was higher in those receiving FEPD. The crude recurrence rates in FCD- and FEPD-treated patients were 20.0% and 10.7%, respectively (OR:0.48; 95% CI 0.22–1.05; P = 0.068). We did not find any differences in CDI recurrence rate in patients receiving FEPD versus FCD (OR = 0.74; 95% CI 0.27–2.04) by propensity score analysis.
Conclusions
Although the recurrence rate with FEPD was numerically lower than that observed with FCD, we have not been able to show that the recurrence rate of CDI is different depending on the dosage regimen of fidaxomicin. Clinical trials or large observational studies comparing the two dosing regimens of fidaxomicin are needed.
Antiretroviral therapy (ART) has been able to transform HIV infection into a chronic disease. However, ART adherence remains an important barrier and personality traits have been postulated as a ...factor to be considered. This study aims to identify personality traits that can affect ART adherence, taking into account other potentially influencing factors.
Case-control study. Controls and cases were classified using the percentage ART dispensation as recorded in the Hospital Pharmacy database. Controls were defined as people living with HIV/AIDS (PLWHA) with percentage ART dispensation during the last year >95% and cases were defined as PLWHA with percentage ART dispensation during the last year <90%. Sociodemographic, clinical parameters of HIV infection, psychopathological and neuropsychological factors were collected. Personality was assessed using the NEO PI-R Personality Inventory, questionnaire based on the Five Factor Model of Personality. Statistical analysis was performed using logistic regression (SPSS v.22).
125 PLWHA were included: 79 controls and 46 cases. After adjusting for confounding variables, logistic regression analysis showed that poor adherence was associated with Neuroticism (OR 1.2, 95%CI: 1.021–1.385) and Impulsivity (N5) (OR 1.5, 95%CI: 1.066–2.163). In contrast, each additional point in Order (C2) (OR 0.8, 95%CI: 0.679–0.992) or Values (O6) (OR 0.8, 95%CI: 0.710–0.974) were associated with good ART adherence.
Personality is a variable to be considered in ART adherence. Implementation of the personality in the assessment of PLWHA helps identify those individuals potentially more likely to exhibit poorer ART adherence.
•Personality has been suggested as a risk factor for antiretroviral therapy (ART).•High levels of Neuroticism and Impulsivity are associated with poor ART adherence.•High levels of Order and Values are associated with good ART adherence.•Personality should be regarded as a further variable of interest in ART adherence.
This study aimed to analyze the prevalence of sexualized drug use (SDU) and determine its association with a comprehensive set of sociodemographic characteristics, risky sexual behaviors, prevention ...measures for human immunodeficiency virus (HIV) and other sexually transmitted infections (STI), and STI diagnosis in Spain.
The sample consisted of 493 men who have sex with men between 18 and 78 years old (M age = 32.58, SD = 11.05).
Approximately 37.9% of the participants had participated in SDU. Participants who practiced SDU were significantly more likely to be older and have more casual sexual partners and engage in less conventional sexual practices than those who did not. In addition, SDU was associated with less consistent condom use and greater use of Pre-Exposure Prophylaxis (PrEP) compared to participants who did not practice SDU. Finally, the STI diagnosis was also significantly related to SDU. However, when condom use and PrEP was included and controlled in the model along with STI diagnosis, SDU was no longer related to a higher likelihood of STI diagnosis.
These results reveal the need to strengthen programs to foster risk-reduction behaviors and reduce the incidence of health implications associated with SDU.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objective To estimate the prevalence of hepatitis B virus (HBV) infection and vaccine-induced immunity in the region of Madrid, and to analyze their evolution over time. Methods An ...observational, analytical, cross-sectional study was carried out in the population aged 16–80 years between 2008 and 2009. This was the last of four seroprevalence surveys in the region of Madrid. The prevalence of HBV infection and vaccine-induced immunity was estimated using multivariate logistic models and were compared with the prevalences in the 1989, 1993 and 1999 surveys. Results In the population aged 16–80 years, the prevalence of HBV infection was 11.0% (95% CI: 9.8–12.3) and that of chronic infection was 0.7% (95% CI: 0.5–1.1). The prevalence of vaccine-induced immunity in the population aged 16–20 years was 73.0% (95% CI: 70.0–76.0). Compared with previous surveys, there was a decrease in the prevalence of HBV infection. Conclusions Based on the prevalence of chronic infection (<1%), Madrid is a region with low HBV endemicity. Preventive strategies against HBV should especially target the immigrant population.
Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised ...individuals with COVID-19 among a cohort of HIV-infected adults in Madrid.
In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19.
51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3-2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per μL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts.
HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population.
None.
A high proportion of people who have suffered from COVID-19 report, after recovery from the acute phase of the disease, clinical manifestations, both subjective and objective, that continue beyond 3 ...weeks or even 3 months after the original clinical disease. There is still no agreed nomenclature to refer to this condition, but perhaps the most commonly used is post-COVID syndrome. The Scientific Committee on COVID of the Madrid College of Physicians (ICOMEM) has discussed this problem with a multidisciplinary approach in which internists, infectious disease specialists, psychiatrists, pneumologists, surgeons, geriatricians, pediatricians, microbiologists, family physicians and other specialists have participated, trying to gather the existing information and discussing it in the group. The clinical manifestations are very variable and range from simple fatigue to persistent fibrosing lung lesions with objective alterations of pulmonary function. Post-COVID syndrome seems to be particularly frequent and severe in adults who have required admission to Intensive Care Units and has a peculiar behavior in a very small group of children. The post-COVID syndrome, which undoubtedly exists, is at first sight not clearly distinguishable from clinical manifestations that which occur after other acute viral diseases and after prolonged stays in ICUs due to other diseases. Therefore, it offers excellent research opportunities to clarify its pathogenesis and possibly that of other related entities. It is possible that progressively there will be an increased demand for care among the millions of people who have suffered and overcome acute COVID for which the health authorities should design mechanisms for the agile management of care that will possibly require well-coordinated multidisciplinary groups. This paper, structured in questions on different aspects of the post-COVID syndrome, attempts to stage the current state of this problem.