Drug combination therapy for emerging viral diseases

Drug Discovery Today, Journal Year: 2021, Volume and Issue: 26(10), P. 2367 - 2376

Published: May 21, 2021

Effective therapeutics to combat emerging viral infections are an unmet need. Historically, treatments for chronic with single drugs have not been successful, as exemplified by human immunodeficiency virus (HIV) and hepatitis C (HCV) infections. Combination therapy these diseases has led improved clinical outcomes dramatic reductions in load, morbidity, mortality. Drug combinations can enhance therapeutic efficacy through additive, ideally synergistic, effects re-emerging viruses, such influenza, severe acute respiratory syndrome-coronavirus (SARS-CoV), Middle East syndrome (MERS)-CoV, Ebola, Zika, SARS-coronavirus 2 (CoV-2). Although novel drug development traditional pipelines remains a priority, the interim, effective synergistic candidates could be rapidly identified drug-repurposing screens, facilitating accelerated paths testing potential emergency use authorizations.

Language: Английский

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Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 219 - 219

Published: Jan. 31, 2024

Chronic Human Immunodeficiency Virus (HIV) infection remains a significant challenge to global public health. Despite advances in antiretroviral therapy (ART), which has transformed HIV from fatal disease into manageable chronic condition, definitive cure elusive. One of the key features is immune activation and inflammation, are strongly associated with, predictive of, progression, even patients successfully treated with suppressive ART. inflammation characterized by persistent cell metabolic dysregulation, cellular exhaustion dysfunction. This review aims summarize current knowledge interplay between metabolism, T dysfunction infection, also discusses use humanized mice models study pathogenesis develop novel therapeutic strategies.

Language: Английский

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Designing a multi-epitope vaccine targeting the HIV-1 subtype CRF01_AE in Indonesia

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 187, P. 109758 - 109758

Published: Jan. 30, 2025

Language: Английский

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Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 23(1), P. 280 - 280

Published: Dec. 28, 2021

Viral infections have afflicted human health and despite great advancements in scientific knowledge technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need review evidence impact of nutritional strategies maintain healthy immune system, particularly instances where there are limited therapeutic treatments. Selenium, an essential trace element humans, long history lowering occurrence severity viral infections. Much benefits derived from selenium due its incorporation into selenocysteine, important component proteins known as selenoproteins. associated with increase reactive oxygen species may result oxidative stress. Studies suggest that deficiency alters response infection by increasing stress rate mutations genome, leading pathogenicity damage host. This examines infections, including novel SARS-CoV-2, context selenium, order inform potential system.

Language: Английский

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Cardiac and Renal Comorbidities in Aging People Living With HIV

Circulation Research, Journal Year: 2024, Volume and Issue: 134(11), P. 1636 - 1660

Published: May 23, 2024

Contemporary World Health Organization data indicates that ≈39 million people are living with the human immunodeficiency virus. Of these, 24 have been reported to successfully accessed combination antiretroviral therapy. In 1996, endorsed widespread use of therapy, transforming virus infection from being a life-threatening disease chronic illness characterized by multiple comorbidities. The increased access therapy has translated (PLWH) no longer having reduced life expectancy. Although aging as biological process increases exposure oxidative stress and subsequent systemic inflammation, this effect is likely enhanced in PLWH they age. This narrative review engages intricate interplay between associated cardiac renal comorbidities development PLWH. We examine evolving demographic profile PLWH, emphasizing increasing prevalence individuals within population. A central focus discusses pathophysiological mechanisms underpin heightened susceptibility diseases

Language: Английский

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Beyond HIV Shame: Effects of Self-Forgiveness in Improving Mental Health in HIV-Positive Individuals in Poland

Journal of Religion and Health, Journal Year: 2024, Volume and Issue: 63(6), P. 4232 - 4254

Published: Aug. 3, 2024

Abstract Guided by the bio-psycho-socio-spiritual approach, this randomized controlled trial assessed efficacy of a self-forgiveness intervention among 60 HIV-positive individuals in Poland. Participants underwent 90-min "Restore: The Journey Toward Self-Forgiveness" session, contrast to wait-list control group. significantly enhanced self-forgiveness, spirituality, mental well-being, and heart rate variability response cognitive stressor (i.e., arithmetic challenge). Significant effects were observed both between-group within-subject comparisons. These results support incorporation into psychological rehabilitation programs for HIV improve quality life health outcomes.

Language: Английский

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Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: June 18, 2021

White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity. Several AT’s intrinsic features favor its key role local and systemic inflammation: (i) large distribution throughout body, (ii) major endocrine activity, (iii) presence metabolic immune cells close proximity. In obesity, concomitant pro-inflammatory signals produced by cells, adipocytes stem help drive a vicious circle. Although secretion adipokines AT is prime contributor inflammation, lipotoxicity associated with dysfunction might also be involved could affect distant organs. HIV-infected patients, targeted both HIV infection antiretroviral therapy (ART). During primary phase infection, virus targets directly (by infecting CD4 T cells) indirectly (via viral protein release, inflammatory signals, gut disruption). The initiation ART drastically changes picture: reduces load, restores (at least partially) cell count, dampens processes on whole-body level but within AT. However, induces side effects, which are highly dependent individual molecules combination used. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA induce oxidative stress adipocyte death. Protease pathways (affecting adipogenesis homeostasis) resulting insulin resistance. Recently marketed integrase strand transfer adipogenesis, hypertrophy fibrosis. It challenging distinguish between respective effects persistence, persistent defects toxicity profile present ART-controlled patients. host status, size pre-established reservoir, quality restoration, natural ageing comorbidities may mitigate and/or reinforce contribution antiretrovirals (ARVs) development low-grade Protecting functions appears relevant requires lifestyle habits improvement absence effective anti-inflammatory treatment. Besides, reducing toxicities remains crucial therapeutic goal.

Language: Английский

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Influence of cytokines on the recovery trajectory of HIV patients on antiretroviral therapy: A review

Medicine, Journal Year: 2025, Volume and Issue: 104(1), P. e41222 - e41222

Published: Jan. 3, 2025

Cytokines, critical signaling molecules in the immune system, significantly influence pathophysiology of Human Immunodeficiency Virus (HIV) infection and effectiveness antiretroviral therapy (ART). Dysregulated cytokine production, characterized by elevated pro-inflammatory anti-inflammatory cytokines, plays a pivotal role chronic inflammation activation untreated HIV patients. ART initiation leads to changes levels, typically resulting decreased systemic inflammation, though extent persistence these vary among individuals. Despite successful viral suppression with ART, many patients experience persistent driven ongoing dysregulation. This inflammatory state is associated adverse clinical outcomes, including cardiovascular disease, neurocognitive impairment, non-AIDS-related cancers. Understanding specific profiles that contribute outcomes crucial for developing targeted therapeutic interventions improve long-term health. Cytokine modulation presents promising avenue enhancing recovery reducing on ART. Identifying patterns serve as biomarkers disease progression treatment response can help tailor individualized strategies. Future research should focus adjunctive therapies target activity mitigate residual thereby improving overall health quality life

Language: Английский

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Do Nurse Practitioners Deliver? A Retrospective Self-audit Comparing Nurse Practitioner Care for People With HIV in Australia to Screening and Monitoring Guidelines

Journal of the Association of Nurses in AIDS Care, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract In Australia, nurse practitioners (NPs) provide care to people with HIV (PWH) in hospital and community settings. We describe a national audit evaluating NP for PWH, assessing adherence 2 monitoring guidelines. Five NPs conducted retrospective case note self-audit. Deidentified data were collected, pooled, analyzed using Microsoft Excel compared guideline targets. The review was undertaken 212 patients, the majority being cisgendered men (86%), ages 45–49 years, identifying as gay (65%). (95%) of PWH on an appropriate treatment, meeting United Nations Programme HIV/AIDS target 95%. viral load testing current 211 (99%) individuals. Of 138 individuals eligible cardiovascular screening, 84 (60%) screened, below 90%. Compliance guidelines exceeded targets most areas. Our demonstrates that effective compliant Australia.

Language: Английский

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Biomarkers of inflammation and coagulation predict non‐AIDS‐defining events in a prospective cohort of virologically suppressed people living with HIV

HIV Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

To assess the association between biomarkers of inflammation, coagulation and immune activation incidence non-AIDS-defining events in a contemporary, antiretroviral therapy (ART)-experienced virologically suppressed cohort people living with HIV (PLWH). Prospective, observational study. PLWH aged 30-70 years, undetectable viral load no history cardiovascular disease, randomly selected from outpatients were included. At baseline, plasma (high-sensitivity C-reactive protein [hs-CRP], sCD163, sCD14, D-dimer, interleukin-6, soluble vascular cell adhesion molecule [s-VCAM] lipoprotein-associated phospholipase A2 [Lp-PLA2] activity) measured. Non-AIDS-defining (non-AIDS cancer events) non-AIDS death recorded until November 2022. Cumulative was analysed for each endpoint adjusted Cox regression used to associations. A total 438 participants included: 81.1% men, mean age 50.4 (SD 10.1) years. The median time on treatment 15.5 (interquartile range [IQR] 8.69; 19.7) years 7.05 (IQR 4.03; 11.6) 77 70 patients (38 cancers, 21 events, 37 deaths) follow-up 6.72 6.02; 7.36) cumulative cancer, event 8.7% (95% CI 6.2-11.7), 4.79% 2.99-7.24) 8.47% 6-11.5), respectively. In models, sCD163 associated incident (hazard ratio [HR] 1.23, 95% 1.08-1.39), hs-CRP (HR 1.61, 1.05-2.47), 1.28, 1.11-1.46) D-dimer 1.75, 1.08-2.86) death. Biomarkers monocyte contemporary long-term PLWH.

Language: Английский

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