Antiviral Therapy最新文献

Background: COVID-19 has become the center of attention since its outbreak in December 2019. Despite the discovery of its preventive vaccine, role of healthy immune system is undebatable. Functional foods are continuously hunted as a promising option for a safe natural therapeutic treatment.Purpose: This review demonstrates how functional foods can boost host immune system, promote antiviral operation, and synthesize biologically effective molecules against SARS-COV-2.Research Methodology: For current review, online search was conducted for nature-based functional immune boosters against SARS-COV-2.Conclusion: Functional foods, alongside a healthy lifestyle, fortifies the human immune system and could all help to dramatically lower the cost burden of COVID-19, the suffering of the patients, and the mortality rates worldwide.

ObjectiveTo explore the durability of multi-drug antiretroviral regimens in treatment-experienced PWH.DesignThis retrospective observational study including PWH who started mega-ART regimens between 1 January 2009 and 31 December 2019, selected from the ARCA cohort.MethodsTime-dependent events were analysed by Kaplan-Meier methods, while Cox regression models were used to define the predictors of mega-ART discontinuation.ResultsA total of 1,514 ART-experienced PWH were included. Over a median follow-up of 47 weeks (IQR 15-127), 1,299 (83%) mega-ART were interrupted, with an incidence of 85.62 per 100 person-years of follow-up. In the multivariable analysis, predictors of higher risk of mega-ART discontinuation were a higher number of antiretroviral drugs included in baseline regimens (aHR 1.206, CI 95% 1.016-1.431, p = .032) and a higher baseline HIV RNA log₁₀ (aHR 1.113, CI 95% 1.048-1.181, p < .001); otherwise, shorter duration of previous ART was associated with a lower risk of discontinuation (aHR 0.982, CI 95% 0.965-0.999, p = .037). When mega-ART was stopped, 299 PWH (23%) had HIV RNA levels above 50 copies/ml, 16/299 (1%) had HIV RNA levels >50 copies/ml but less than 200 copies/ml, 792 PWH (61%) had HIV RNA levels below 50 copies/ml, and 208 PWH (16%) had an undetermined HIV RNA load.ConclusionsMega-ART was characterized by limited durability and poor virological success.

Introduction: Photodynamic therapy (PDT) is a two-stage treatment method making use of light energy and a photosensitizer in the presence of oxygen. PDT has already proved to bring good anti-inflammatory and anti-proliferative effects in the treatment of actinic keratosis, squamous cell carcinoma in situ as well as in superficial and nodular basal cell carcinoma. In PDT-treated lesions, infected or cancerous keratinocytes are effectively destroyed due to selective apoptosis and necrosis induced by a release of reactive oxygen species. PDT is distinguished by several features, most notably its non-invasiveness, selectivity for the target tissue, which causes fewer side effects and brings excellent cosmetic results. PDT is an effective option for treating viral diseases using a photosensitizer capable of selective accumulation in virus-infected cells not only within visible lesions, but also in subclinical disease areas where the virus is in latent form. Objectives and methods: This literature review presents recent reports on PDT for the treatment of viral skin infections, with a particular focus on the efficacy of this method. Results: The viruses that most commonly cause skin diseases include the human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), molluscum contagiosum virus (MCV). PDT inhibits the proliferation of virus-infected cells, induces apoptosis, damages lesional blood vessels, regulates local immunity and controls viral loads. An additional advantage of PDT is the short healing period and little damage to the treated tissue. Furthermore, wider use of PDT may contribute to reducing the risk of developing drug resistance. Conclusion: The safety of PDT makes this method an effective way to treat viral skin diseases in difficult locations, as well as in children and immunocompromised patients.

ObjectivesTo determine seroprevalence, seroconversion, and mother-to-child transmission (MTCT) rates for dual and triplex infections of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among pregnant women.MethodsA multicentre prospective cohort study was conducted in six randomly selected tertiary hospitals from six geopolitical zones of Nigeria. Consenting participants were tested at recruitment for triplex infections and followed-up till delivery. Retests were performed at delivery for those who tested negative for all three infections/positive for only one. Polymerase chain reaction was used for validation while rapid test kits were employed for initial screening.ResultsOf the 2775 participants recruited, 13 (0.47%; 95% CI: 0.25%-0.80%) and 4 (0.14%; 95% CI: 0.04%-0.37%) were seropositive for dual and triplex infections, respectively. Dual infections revealed seroprevalences of 0.22% for HIV-HBV (6/2775; 95% CI: 0.08%-0.47%), 0.14% for HIV-HCV (4/2775; 95% CI: 0.04%-0.37%), and 0.11% for HBV-HCV (3/2775; 95% CI: 0.02%-0.32%). Multivariable analysis highlighted significant associations between HIV/HBV co-infection and religion (adjusted odds ratio (aOR): 0.068, 95% CI: 0.006-0.757) and house ownership (aOR): 1.65 × 10^-9, 95% CI: 1.60 × 10^-9-1.70 × 10^-9). Continuing our follow-up until delivery for 2403 initial participants, 2386 did not have dual or triplex infections at the start. Upon retesting at delivery, three of these women were seropositive for a dual infection of HIV and HBV, giving a seroconversion rate of 0.12% (95% CI: 0.03% to 0.37%). MTCT rate stood at 0% at 6-week post-delivery.ConclusionWe observed a relatively low seroprevalence and seroconversion rates for dual and triplex infections of HIV, HBV, and HCV among pregnant women in Nigeria and no MTCT.

Dolutegravir 50 mg twice daily (BID) dosing is currently recommended in presence of strong inducers of drug metabolism. However, this dosing has been challenged by studies showing similar rates of viral suppression with dolutegravir once daily (QD) compared to BID dosing in presence of the strong inducer rifampicin. We report the case of a 41-year-old man with sustained virological suppression and documented therapeutic dolutegravir concentration on once daily dosing while treated with the strong inducer carbamazepine. Therapeutic drug monitoring can guide the need for twice daily dosing dolutegravir in presence of strong inducers.

Background: Integrase strand transfer inhibitors (INSTIs) have been associated with excess weight gain in people living with HIV compared to other antiretroviral agents. The mechanisms that underlie these effects are not well defined. Thus, we aimed to examine the effects of switching to INSTI-containing regimens on clinical metabolic parameters.

Setting: A secondary analysis of a prospective cohort study in which people living with HIV on a stable efavirenz-based regimen were switched to a cobicistat-boosted elvitegravir or raltegravir-containing regimen. Participants remained on the NRTI backbone of tenofovir disoproxil fumarate and emtricitabine.

Methods: Frozen plasma samples from 19 participants were used to determine concentrations of leptin, adiponectin, insulin and lactate at baseline and 8 weeks post-switch. Fasting lipids and blood glucose not reported in the initial study were obtained to examine metabolic changes. Anthropometric data including height and weight were abstracted from the medical record.

Results: Participants switched from efavirenz to cobicistat-boosted elvitegravir without change in tenofovir disoproxil fumarate/emtricitabine backbone showed a 20% increase in HOMA-IR after 8 weeks (1.84 vs 2.24, p < .05), due mostly to increases in fasting insulin. This increase occurred independent of weight gain in the cohort as whole (83.4 vs 85.9 kg, pre vs post, p = .04), but was linked to increases in circulating lactate.

Conclusions: Participants switched to an INSTI-based regimen tended to gain weight, and those switched to cobicistat-boosted elvitegravir had increases in markers of insulin resistance and elevation in plasma lactic acid compared to raltegravir, suggesting that elvitegravir may promote metabolic perturbations in people living with HIV.

Background: Molnupiravir (MOV) is an orally bioavailable ribonucleoside with antiviral activity against all tested SARS-CoV-2 variants. We describe the demographic, clinical, and treatment characteristics of non-hospitalized Danish patients treated with MOV and their clinical outcomes following MOV initiation.

Method: Among all adults (>18 years) who received MOV between 16 December 2021 and 30 April 2022 in an outpatient setting in Denmark, we summarized their demographic and clinical characteristics at baseline and post-MOV outcomes using descriptive statistics. Outcomes were emergent hospitalization and all-cause mortality during the 28 days after MOV initiation. We estimated the odds ratios (OR) of outcomes by time from positive test to treatment using logistic regression.

Results: We identified 3691 MOV-treated patients, of whom 45.8% were male and mean age was 70.1 years. Most patients (76.2%) initiated MOV within 0-2 days after a positive SARS-CoV-2 test and 16.8% within 3-5 days. Over a 28-day period, rates for all-cause, respiratory- or COVID-19-related, and COVID-19-related hospitalization were 4.8%, 2.6% and 1.5%, respectively. All-cause mortality was 1.6%. Initiation of MOV 3-5 days after a positive SARS-CoV-2 test compared to 1-2 days was associated with an increased risk of all-cause (OR 1.85, 95% CI 1.29-2.67) and respiratory or COVID-19-related (OR 1.78, 95% CI 1.07-2.94) hospitalization, and all-cause mortality (OR 2.90, 95% CI 1.64-5.15).

Conclusion: MOV was primarily prescribed to vaccinated elderly persons with multiple comorbidities. The all-cause hospitalization and mortality rates in this population were low. Early initiation of MOV reduced the risk of hospitalization and death compared with late initiation.

Background: Nirmatrelvir has been shown to reduce morbidity and mortality associated with COVID-19. However, it is underutilized due to concerns regarding COVID-19 symptom rebound following nirmatrelvir's standard 5-day course. This study aims to identify and evaluate a nirmatrelvir dosage regimen that lowers symptom rebound.

Methods: Based on nirmatrelvir pharmacokinetics, we propose a novel 8-day regimen: two doses twice-daily followed by six doses once-daily to reduce rebound frequency. We then carried out a retrospective case series study of clinical outcomes among our patients to investigate their frequency of COVID-19 symptom rebound following nirmatrelvir usage.

Results: Among the 58 prescribed case patients, 49 filled and initiated the prescription. Of those 49 patients, four took the medication for fewer than 5 days, 24 for 5 days (standard regimen), and 21 for 7 or 8 days (extended regimen). Among 5-day treatment cases (n = 24), 8 (33%) experienced clinical rebound, whereas among the 7-day or 8-day treatment cases (n = 21), 2 (9.5%) experienced rebound.

Conclusions: These findings suggest that a longer nirmatrelvir/ritonavir course might reduce rebound symptoms compared to the standard 5-day regimen.

Background: The COVID-19 pandemic has created an urgent need for effective therapeutic agents. The SARS-CoV-2 Main Protease (M^pro) plays a crucial role in viral replication and immune evasion, making it a key target for drug development. While several studies have explored M^pro inhibition, identifying FDA-approved drugs with potential efficacy remains a critical research focus.

Purpose: This study aims to identify FDA-approved drugs that could inhibit SARS-CoV-2 M^pro. Using computational screening, we seek compounds that share structural similarities with a known co-crystallized ligand (PRD_002214) and exhibit strong binding affinity to the enzyme, providing viable candidates for COVID-19 treatment.

Research design: A systematic in silico approach was used, screening 3009 FDA-approved drugs. The initial screening focused on structural similarity to PRD_002214 (PDB ID: 6LU7), followed by molecular docking studies to predict binding affinity. Promising compounds were further analyzed through molecular dynamics (MD) simulations to evaluate their stability and interactions with M^pro over 100 ns.

Study sample: Of the 3009 FDA-approved drugs screened, 74 were selected for initial evaluation. After refinement, 28 compounds underwent docking analysis, with eight showing strong binding potential to M^pro.

Analysis: Molecular docking assessed the binding affinity and interaction of the selected compounds with M^pro. MD simulations were conducted on the top compound, Atazanavir, to study its dynamic interactions. MM-GBSA, PLIP, and PCAT analyses were used to validate binding affinity and interactions.

Results: Eight compounds, including Carfilzomib, Atazanavir, Darunavir, and others, exhibited promising binding affinities. Among them, Atazanavir showed the highest binding strength and was selected for further MD simulation studies. These simulations revealed that Atazanavir forms stable interactions with M^pro, demonstrating favorable binding and dynamic stability. The binding affinity was further confirmed through MM-GBSA, PLIP, and PCAT analyses, supporting Atazanavir's potential as an effective M^pro inhibitor.

Conclusions: In silico results suggest that Atazanavir is a promising candidate for targeting SARS-CoV-2 M^pro, with strong binding affinity and dynamic stability. These findings support its potential as a lead compound for further preclinical and clinical testing, though in vitro and in vivo validation are needed to confirm its therapeutic efficacy against COVID-19.

Introduction: BIC/FTC/TAF showed efficacy and tolerability in randomized trials as a switch strategy in virologically-suppressed people living with HIV. We evaluated its effectiveness in a real-life setting.

Methods: A retrospective monocentric cohort including 431 virologically-suppressed (HIV-RNA <50 copies/ml) people switching to BIC/FTC/TAF in the period 2018-2022 was evaluated. Probabilities of virological failure (VF, i.e.2 consecutive HIV-RNA ≥50 copies/ml or a single HIV-RNA ≥200 copies/ml) and of treatment discontinuation (TD) were estimated by Kaplan-Meier, and predictors of both outcomes were identified through multivariable Cox regression. Analysis-of-variance for repeated measures was used to examine changes in CD4 count and CD4-to-CD8 ratio.

Results: Overall, 16 VF occurred during 22 months of median follow-up time. Estimated probabilities of VF at 1, 2 and 3 years were 2.0% (95% CI 1.04.2%), 2.9% (95% CI 1.5%-5.6%) and 5.5% (95% CI 3.2%-9.2%), respectively. Caucasian ethnicity and a history of previous VF independently predicted VF. TD occurred in 42 cases, predominantly for simplification. One discontinuation due to VF was reported. No predictors of discontinuation were identified. An increase in CD4-to-CD8 ratio over 3 years was evidenced (p < 0.001). Total cholesterol decreased over 3 years (p < 0.001). Triglycerides did not significantly change (p = 0.465).

Conclusions: BIC/FTC/TAF demonstrated high effectiveness, tolerability and safety.