scholarly journals Evaluation of several serum interleukins as markers for treatment effectiveness in naïve HIV infected patients: A pilot study

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260007
Author(s):  
Cristian Jianu ◽  
Corina Itu-Mureşan ◽  
Cristina Drugan ◽  
Irina Filipescu ◽  
Adriana Violeta Topan ◽  
...  
Keyword(s):  
Pilot Study ◽  
Immune Activation ◽  
Treatment Effectiveness ◽  
Standard Of Care ◽  
P Value ◽  
Random Allocation ◽  
Strand Transfer ◽  
Activation Markers ◽  
Immunodeficiency Virus ◽  
The Impact

In this observational pilot study, we investigated the impact of Dolutegravir, Raltegravir, Elvitegravir (Integrase Strand Transfer Inhibitors, INSTIs), or boosted Darunavir (a Protease Inhibitor, PI) in combination with two nucleoside reverstranscriptase inhibitors (Emtricitabine/Tenofovir disoproxil or Lamivudine/Tenofovir disoproxil, NRTI) on four interleukins (IL-4, IL-10, IL-13, and IL-21) as immune activation markers in naïve HIV(Human Immunodeficiency Virus)-infected patients during the first six months of combined standard-of-care antiretroviral therapy (cART). Newly diagnosed with HIV-infected subjects and without any disease that could affect the immune activation markers were evaluated. The patients’ physicians recommended the cART as standard-of-care and the ILs were measured before cART and six months of cART. The levels of CD4+ T-cells count and CD4+/CD8+ ratio significantly increased at six months (P-value<0.02) regardless of the drugs, INSTIs or PI. However, a CD4+/CD8+ >1 was observed in 25% of patients treated with Raltegravir and half of those treated with Dolutegravir. At six months of cART, viral load was detectable in only 6/31 individuals. IL-21 had an undetectable level in 30/31 patients after six months of cART. Our results suggest the potency in restoring immune markers in HIV-infected patients with all investigated drugs. Dolutegravir showed a tendency to statistically significant changes in IL-4 and IL-10. A clinical trial with random allocation of medication and an extensive follow-up is needed to replicate this research and validate the usefulness of evaluated ILs as markers of cART effectiveness.

scholarly journals A Pilot Study of Immune Activation and Rifampin Absorption in HIV-Infected Patients without Tuberculosis Infection: A Short Report

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Christopher Vinnard ◽  
Isabel Manley ◽  
Brittney Scott ◽  
Mariana Bernui ◽  
Joella Adams ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Pilot Study ◽  
Bacterial Translocation ◽  
Immune Activation ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Short Report ◽  
Hiv Viral Load ◽  
Time Curve ◽  
Immunodeficiency Virus

Background. Rifampin malabsorption is frequently observed in tuberculosis patients coinfected with human immunodeficiency virus (HIV) but cannot be predicted by patient factors such as CD4+ T cell count or HIV viral load. Methods. We sought to describe the relationship between HIV-associated immune activation, measures of gut absorptive capacity and permeability, and rifampin pharmacokinetic parameters in a pilot study of 6 HIV-infected, tuberculosis-uninfected patients who were naïve to antiretroviral therapy. Results. The median rifampin area under the concentration-versus-time curve during the 8-hour observation period was 42.8 mg·hr/L (range: 21.2 to 57.6), with a median peak concentration of 10.1 mg/L (range: 5.3 to 12.5). We observed delayed rifampin absorption, with a time to maximum concentration greater than 2 hours, in 2 of 6 participants. There was a trend towards increased plasma concentrations of sCD14, a marker of monocyte activation in response to bacterial translocation, among participants with delayed rifampin absorption compared to participants with rapid absorption (p=0.06). Conclusions. Delayed rifampin absorption may be associated with elevated markers of bacterial translocation among HIV-infected individuals naïve to antiretroviral therapy. This trial is registered with NCT01845298.

scholarly journals The Effect of Rosuvastatin on Markers of Immune Activation in Treatment-Naive Human Immunodeficiency Virus-Patients

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Robyn G. M. Weijma ◽  
Eric R. A. Vos ◽  
Jaap Ten Oever ◽  
Muriel Van Schilfgaarde ◽  
Lea M. Dijksman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Activation ◽  
Immune Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Activation Markers ◽  
Cell Ratio ◽  
Immunodeficiency Virus ◽  
Treatment Naïve

Abstract Background.  Immune activation has been implicated in the excess mortality in human immunodeficiency virus (HIV)-infected patients, due to cardiovascular diseases and malignancies. Statins may modulate this immune activation. We assessed the capacity of rosuvastatin to mitigate immune activation in treatment-naive HIV-infected patients. Methods.  In a randomized double-blind placebo-controlled crossover study, we explored the effects of 8 weeks of rosuvastatin 20 mg in treatment-naive male HIV-infected patients (n = 28) on immune activation markers: neopterin, soluble Toll-like receptor (TLR)2, sTLR4, interleukin (IL)-6, IL-1Ra, IL-18, d-dimer, highly sensitive C-reactive protein, and CD38 and/or human leukocyte antigen-DR expression on T cells. Baseline data were compared with healthy male controls (n = 10). Furthermore, the effects of rosuvastatin on HIV-1 RNA, CD4/CD8 T-cell count, and low-density lipoprotein cholesterol were examined and side effects were registered. Results.  T-cell activation levels were higher in patients than in controls. Patients had higher levels of circulating IL-18, sTLR2, and neopterin (all P &lt; .01). Twenty patients completed the study. Rosuvastatin increased the CD4/CD8 T-cell ratio (P = .02). No effect on other markers was found. Conclusions.  Patients infected with HIV had higher levels of circulating neopterin, IL-18, sTLR2, and T-cell activation markers. Rosuvastatin had a small but significant positive effect on CD4/CD8 T-cell ratio, but no influence on other markers of T-cell activation and innate immunity was identified (The Netherlands National Trial Register [NTR] NTR 2349, http://www.trialregister.nl/trialreg/index.asp).

scholarly journals Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills (Mandrillus sphinx)

2006 ◽  
Vol 80 (7) ◽  
pp. 3301-3309 ◽  
Author(s):  
Richard Onanga ◽  
Sandrine Souquière ◽  
Maria Makuwa ◽  
Augustin Mouinga-Ondeme ◽  
François Simon ◽  
...  
Keyword(s):  
Viral Replication ◽  
Simian Immunodeficiency Virus ◽  
T Cell Activation ◽  
Primary Infection ◽  
Chronic Phase ◽  
Viral Control ◽  
Activation Markers ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
The Impact

ABSTRACT Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4+ and CD8+ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 107 to 108 RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 105 to 106 RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (105 to 106 DNA copies/106 cells) and stabilized at 103 to 104 DNA copies/106 cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3+ CD4+ cells in the LNs occurred in animals with high peak VLs. CD4+ and CD8+ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.

Raising the standard of care in the treatment of schizophrenia: Yes we can!

2017 ◽  
Vol 51 (5) ◽  
pp. 438-440 ◽  
Author(s):  
Stanley Victor Catts ◽  
Brian O’Toole
Keyword(s):  
Communication Skills ◽  
Critical Review ◽  
Treatment Effectiveness ◽  
Standard Of Care ◽  
Financial Resources ◽  
First Episode ◽  
Published Data ◽  
Decision Making Capacity ◽  
The Impact

Objective: In response to evidence of deteriorating outcomes of people with schizophrenia we recently published a critical review in the journal concerning why outcomes for schizophrenia are not improving. A published commentary on our review raised criticisms that we aim to address herein. Method: Published data related to four issues raised in the commentary were reviewed. Results: There is a body of evidence that supports the possibility of dramatic improvements in treatment effectiveness, presented in our critical review, and these can be achieved within existing financial resources and present day understanding of the pathophysiology of schizophrenia. However, the commentary leads us to highlight four current obstacles to improving treatment effectiveness: (1) the belief of many psychiatrists that long-term antipsychotic medication raises the cardiovascular mortality rate in schizophrenia when the opposite is almost certainly the case; (2) the need to improve psychiatrist training in diagnostic and communication skills, especially with first episode presentations; (3) the requirement for comprehensive and structured assessment of the highly prevalent deficits in insight and decision making capacity associated with schizophrenia; and (4) the need for improved intervention design to minimise the impact of these deficits on treatment choice and refusal. Conclusion: With a sense of professional urgency, a genuinely respectful and caring partnership between clinicians, affected individuals and their families, and researchers, with relative little innovation, we conclude that the standard of care can definitely be raised now in the treatment of schizophrenia.

PP289 Impact Of Regional Human Immunodeficiency Virus Therapeutic Pathway On Prescriptions: The Experience Of The Lazio Region In Italy

2020 ◽  
Vol 36 (S1) ◽  
pp. 25-26
Author(s):  
Rossella Di Bidino ◽  
Cauda Roberto ◽  
Andreoni Massimo ◽  
Antinori Andrea ◽  
Mastroianni Claudio ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Pilot Study ◽  
Ad Hoc ◽  
Hiv Treatment ◽  
Clinical Decisions ◽  
Lazio Region ◽  
First Semester ◽  
Immunodeficiency Virus ◽  
Economic Analyses ◽  
The Impact

IntroductionIn 2017, the Lazio Region (Italy) published a care and therapeutic pathway (Percorso Diagnostico Terapeutico Assistenziale [PDTA]) to guide the choice of treatments for human immunodeficiency virus (HIV) patients. Recommendations were based on clinical and economic criteria to guarantee the most appropriate care and sustainability of the regional National Health Service. Our pilot study was conducted to assess how the PDTA impacts clinical decisions and expenditure. Organizational and economic analyses were based on four HIV treatment centers at the regional level.MethodsAn ad hoc data collection was conducted. Each center provided data on the volume of prescriptions for each treatment option for the first semester of 2017 and 2018. The period January-June 2017 (H1-2017) represents the scenario pre-PDTA, while January-June 2018 (H1-2018) provides evidence on the first impact of the PDTA. Expenditure was estimated considering prices reported in the PDTA document. For each center, a semi-structured survey collected evidence on which factors influence treatment decisions.ResultsBetween H1-2017 and H1-2018 the number of experienced patients increased 10.1 percent (6,580 versus 7,249, respectively), while that of naive patients decreased 3 percent (227 versus 220). More than 80 percent of naive patients were treated with regimes recommended by the PDTA versus 36 percent in H1-2017 and 62 percent in H1-2018 of experienced patients. Regimes with a monthly cost > EUR 700 were preferred. The survey showed that the PDTA is a useful tool for supporting clinical decisions.ConclusionsOur pilot study provides a snapshot on the impact of a regional HIV PDTA and identifies key aspects for its future update. Personalization of HIV therapies for an aging (5–29% of patients were >65 years in the four centers) and complex (>65% of patients had at least one comorbidity) population should be discussed for a PDTA update. Posology and treatment adherence should be further investigated.

scholarly journals Nutritional Immunity, Zinc Sufficiency, and COVID-19 Mortality in Socially Similar European Populations

2021 ◽  
Vol 12 ◽  
Author(s):  
Samer Singh ◽  
Amita Diwaker ◽  
Brijesh P. Singh ◽  
Rakesh K. Singh
Keyword(s):  
Standard Of Care ◽  
Protective Role ◽  
Vulnerable Groups ◽  
P Value ◽  
Negative Effects ◽  
Nutritional Immunity ◽  
Incidence And Mortality ◽  
Standard Of Care Treatment ◽  
The Impact ◽  
European Populations

The impact of zinc (Zn) sufficiency/supplementation on COVID-19-associated mortality and incidence (SARS-CoV-2 infections) remains unknown. During an infection, the levels of free Zn are reduced as part of “nutritional immunity” to limit the growth and replication of pathogen and the ensuing inflammatory damage. Considering its key role in immune competency and frequently recorded deficiency in large sections of different populations, Zn has been prescribed for both prophylactic and therapeutic purposes in COVID-19 without any corroborating evidence for its protective role. Multiple trials are underway evaluating the effect of Zn supplementation on COVID-19 outcome in patients getting standard of care treatment. However, the trial designs presumably lack the power to identify negative effects of Zn supplementation, especially in the vulnerable groups of elderly and patients with comorbidities (contributing 9 out of 10 deaths; up to &gt;8,000-fold higher mortality). In this study, we have analyzed COVID-19 mortality and incidence (case) data from 23 socially similar European populations with comparable confounders (population: 522.47 million; experiencing up to &gt;150-fold difference in death rates) and at the matching stage of the pandemic (March 12 to June 26, 2020; first wave of COVID-19 incidence and mortality). Our results suggest a positive correlation between populations’ Zn-sufficiency status and COVID-19 mortality [r (23): 0.7893–0.6849, p-value &lt; 0.0003] as well as incidence [r (23):0.8084–0.5658; p-value &lt; 0.005]. The observed association is contrary to what would be expected if Zn sufficiency was protective in COVID-19. Thus, controlled trials or retrospective analyses of the adverse event patients’ data should be undertaken to correctly guide the practice of Zn supplementation in COVID-19.

scholarly journals Reducing Stress in Youth: A Pilot-Study on the Effects of a University-Based Intervention Program for University Students in Pune, India

2016 ◽  
Vol 6 (2) ◽  
pp. 53 ◽  
Author(s):  
Emma Emily De Wit ◽  
Adithy ◽  
Joske G. F. Bunders-Aelen ◽  
Barbara J. Regeer
Keyword(s):  
Pilot Study ◽  
Perceived Stress ◽  
Mental Health Problems ◽  
Well Being ◽  
Mental Wellbeing ◽  
Health Concern ◽  
P Value ◽  
Base Line ◽  
The Impact

<p>Mental health problems among youth have become important public health concern for many low &amp; middle- income countries. As part of a research program to improve mental wellbeing in Pune, India, a university-based intervention was developed for students of two educational institutes. In one month, 33 students (age 18-22) participated in a series of 2-hour sessions in which they were stimulated to learn better coping skills to deal with stress and anxiety. The interactive sessions were facilitated by a psychologist and volunteers of a suicide prevention NGO. Rational Emotive Behaviour Therapy (REBT) approaches were used to help students identify stressors and find alternative thought patterns towards the stressor. Playful exercises, such as theatre, dance and poetry, were used to develop self-esteem, self-expression and a better sense of control in students. Throughout the program, relaxation methods, such as Emotional Freedom Technique (EFT), were practiced to help reduce stress in students. To study the impact of the intervention, data were collected, before- and after the intervention and in an eight month follow-up with the Perceived Stress Scale (PSS), in combination with open questionnaires and field notes. Preliminary results show a significant decrease in average stress scores in students after the program in comparison to before the intervention (p-value is 0.044 &lt; 0.05). Students reflect upon the program as helpful and specifically emphasize the role of poetry, dance &amp; EFT as main contributors. In follow-up tests perceived stress scores remained lower than at base-line, although not significant. Booster sessions are suggested to sustain the benefits. Overall, the results of this pilot study show that low threshold, university-based interventions, could be useful in stimulating psychosocial well-being in youth.</p><p> </p>

scholarly journals Highly Active Antiretroviral Therapy (HAART) and Circulating Markers of Immune Activation: Specific Effect of HAART on Neopterin

2000 ◽  
Vol 7 (5) ◽  
pp. 832-834 ◽  
Author(s):  
Nathalie Amirayan-Chevillard ◽  
Herve Tissot-Dupont ◽  
Yolande Obadia ◽  
Herve Gallais ◽  
Jean-Louis Mege ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Immune Activation ◽  
Highly Active Antiretroviral Therapy ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Specific Effect ◽  
Activation Markers ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Circulating Markers

ABSTRACT The circulating levels of immune activation markers, including neopterin, tumor necrosis factor receptor type II, and interleukin-2 receptors, are increased in human immunodeficiency virus-infected patients. We show here that highly active antiretroviral therapy significantly decreased neopterin levels. This effect is reversible, since neopterin levels increased after the arrest of treatment. Their determination may be useful in the evaluation of the efficacy of antiretroviral therapy.

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