Antiviral Therapy[JOURNAL]
Sun
200 papers
Nirmatrelvir treatment duration and frequency of COVID-19 rebound.
Sudeep N, Kojima N, Klausner JD
Antivir Ther · 2025 Feb · PMID 39961599 · Publisher ↗
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...
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 ( = 24), 8 (33%) experienced clinical rebound, whereas among the 7-day or 8-day treatment cases ( = 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.
Increased insulin resistance following switch from efavirenz to cobicistat-boosted elvitegravir.
Pickering RT, Asundi A, Olson A … +3 more , Soden K, Kuritzkes DR, Lin NH
Antivir Ther · 2025 Feb · PMID 39953931 · Publisher ↗
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...
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, < .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, = .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.
Clinical outcomes among COVID-19 patients initiated on molnupiravir in Denmark - A national registry study.
Larsen CS, Westergaard CL, Stærke NB … +4 more , Arnet U, Liu G, Kantsø LR, Kjellberg J
Antivir Ther · 2025 Feb · PMID 39836400 · Publisher ↗
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-hospital...
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.
Effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as switch strategy in virologically-suppressed patients: real world data from a monocentric cohort.
Passerotto RA, Lamanna F, Salvo PF … +10 more , Iannone V, Steiner RJ, Carbone A, Farinacci D, D'Angelillo A, Baldin G, Ciccullo A, Di Giambenedetto S, Torti C, Borghetti A
Antivir Ther · 2024 Dec · PMID 39698926 · Publisher ↗
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 r...
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 ( < 0.001). Total cholesterol decreased over 3 years ( < 0.001). Triglycerides did not significantly change ( = 0.465). CONCLUSIONS: BIC/FTC/TAF demonstrated high effectiveness, tolerability and safety.
Repurposing FDA-approved drugs for COVID-19: targeting the main protease through multi-phase approach.
Metwaly AM, Elkaeed EB, Alsfouk AA … +3 more , Ibrahim IM, Elkady H, Eissa IH
Antivir Ther · 2024 Dec · PMID 39639531 · Publisher ↗
BACKGROUND: The COVID-19 pandemic has created an urgent need for effective therapeutic agents. The SARS-CoV-2 Main Protease (M) plays a crucial role in viral replication and immune evasion, making it a key target for dru...
BACKGROUND: The COVID-19 pandemic has created an urgent need for effective therapeutic agents. The SARS-CoV-2 Main Protease (M) plays a crucial role in viral replication and immune evasion, making it a key target for drug development. While several studies have explored M 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. 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 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 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. ANALYSIS: Molecular docking assessed the binding affinity and interaction of the selected compounds with M. 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, 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 inhibitor. CONCLUSIONS: results suggest that Atazanavir is a promising candidate for targeting SARS-CoV-2 M, 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.
Analysis of risk factors and prediction model construction for varicella encephalitis in children: A retrospective cohort study.
Wang C, Tang L, Guo D
Antivir Ther · 2024 Oct · PMID 39413061 · Publisher ↗
INTRODUCTION: This study aimed to analyze the risk factors for varicella encephalitis in children and establish a predictive model. METHODS: This retrospective cohort study included a varicella encephalitis group ( = 75)...
INTRODUCTION: This study aimed to analyze the risk factors for varicella encephalitis in children and establish a predictive model. METHODS: This retrospective cohort study included a varicella encephalitis group ( = 75) and a varicella-non-encephalitis group ( = 135). Logistic regression analysis was employed to find risk factors for varicella encephalitis and create a predictive model. RESULTS: Older age, vomiting, poor mental status, and prolonged rash duration were independent risk factors for varicella encephalitis ( < .05). The predictive model for varicella encephalitis combined above four factors. The ROC curve of the predictive model showed an area under the curve of 0.955 (95% CI 0.925-0.986) for varicella encephalitis in children with a sensitivity of 94.7%, and a specificity of 86.0%. CONCLUSION: Children with varicella who are older, experience vomiting, exhibit poor mental status, or have a prolonged rash duration should be closely monitored clinically. The predictive model combining these four factors demonstrates good predictive efficiency.
Antiviral potential of phenolic compounds against HSV-1: In-vitro study.
Zangooie S, Ghanbari R, Jalilian FA … +2 more , Mahmoudvand S, Teimoori A
Antivir Ther · 2024 Oct · PMID 39311585 · Publisher ↗
BACKGROUND: This in vitro study aimed to investigate the effect of several phenolic compounds, including doxorubicin, quercetin, and resveratrol, on HSV-1 infection. METHODS: The cytotoxicity of the drugs was assessed on...
BACKGROUND: This in vitro study aimed to investigate the effect of several phenolic compounds, including doxorubicin, quercetin, and resveratrol, on HSV-1 infection. METHODS: The cytotoxicity of the drugs was assessed on Vero cells using the MTT assay. HSV-1 was treated with the drugs, and the supernatants were collected at various time points. TCID50% and qPCR tests were conducted on the supernatants to determine viral titration post-inoculation. RESULTS: The TCID50% assay showed significant changes in viral titration for acyclovir, doxorubicin, and quercetin at most concentrations (-value < .05), while no significant changes were observed for resveratrol. The qPCR results demonstrated that drug-treated HSV-1 exhibited a significant reduction in DNA titers at various time points compared to non-treated HSV-1 infected Vero cells, except doxorubicin (0.2 µM) and acyclovir (5 µm). However, over time, DNA virus levels gradually increased in the drug-treated groups. Notably, at certain concentrations of doxorubicin and quercetin-treated groups, virus titer significantly declined, similar to acyclovir. CONCLUSIONS: Our findings suggest that quercetin at concentrations of 62 and 125 µM significantly reduced HSV-1 infectivity, as well as these two concentrations of quercetin showed a significant difference in virus reduction compared with acyclovir (10 µM) at certain time points. The anti-inflammatory properties of quercetin, in contrast to acyclovir, make it a potential candidate for anti HSV-1 treatment in life-threatening conditions such as Herpes encephalitis. Additionally, doxorubicin, an anticancer drug, showed meaningful inhibition of HSV-1 at non-toxic concentrations of 2 and 8 µM, suggesting its potential interference with HSV-1 in viral-oncolytic therapy in cancer treatment.
Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.
Zhang Q, Xu J, Liu D … +6 more , Wang L, Ren S, Zheng S, Chen X, Qi L, Lu J
Antivir Ther · 2024 Oct · PMID 39259839 · Publisher ↗
BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir a...
BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). METHODS: We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF ( = 58) or TAF ( = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. RESULTS: Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF ( = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF ( = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively ( = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. CONCLUSION: TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.
Clinical outcomes in patients with mild to moderate coronavirus disease 2019 treated with monoclonal antibody therapy versus an untreated control cohort.
Nichols CN, Lustberg M, Sobhanie MME … +10 more , Niermann LJ, Gordon M, Kman N, Parsons J, Conroy M, Dick M, Allen J, Reed E, Lehman J, Malvestutto C
Antivir Ther · 2024 Aug · PMID 39066463 · Publisher ↗
BACKGROUND: Monoclonal antibody therapy (MAT) received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for mild to moderate COVID-19 treatment in adults at a high-risk for progression to severe disea...
BACKGROUND: Monoclonal antibody therapy (MAT) received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for mild to moderate COVID-19 treatment in adults at a high-risk for progression to severe disease in November 2020. This study assessed the impact of MAT on clinical outcomes. METHODS: We conducted a single-center, retrospective study comparing 30-day COVID-19-related emergency department (ED) visits, admissions, and mortality in patients receiving MAT (bamlanivimab, bamlanivimab-etesevimab, or casirivimab-imdevimab) between 16 November 2020 and 19 June 2021, compared to a control group of high-risk adults diagnosed with mild to moderate COVID-19 prior to MAT availability between 16 May 2020 and 15 November 2020. Statistical analysis used logistic regression analysis with backward selection to determine the odds ratios and 95% confidence interval evaluating the relationship between clinical characteristics and outcomes. RESULTS: 1187 patients who received MAT were compared to 1103 patients not treated with MAT. Multivariable regression model adjusted for possible confounders showed patients who received MAT had lower rates of ED visits (3.2% vs 7.4%, OR = 0.46, 95% CI = 0.31-0.70, < .001) and hospital admissions (4.3% vs 7.8%, OR = 0.42, 95% CI = 0.29-0.62, < .001) compared to the control group. After adjusting for confounders, MAT was associated with decreased mortality (OR = 0.36, = .035). In the MAT group, those treated within 2 days of COVID-19 diagnosis had lower mortality than those treated more than 2 days post-diagnosis (unadjusted OR = 0.152, 95% CI = 0.031-0.734, = .019). CONCLUSIONS: Individuals treated with MAT had lower rates of 30-day COVID-19-related ED visits and hospital admissions compared to those not receiving MAT. Early MAT resulted in lower 30-day mortality compared to receipt >2 days post COVID-19 diagnosis.
Andrographolide suppresses SARS-CoV-2 infection by downregulating ACE2 expression: A mechanistic study.
Li Q, Lu H, Ruan Y … +5 more , Geng Y, Zhao Z, Liu Y, Feng L, Guo W
Antivir Ther · 2024 Jun · PMID 38873947 · Publisher ↗
Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may have an anti-SARS-CoV-2 effect. In this study, we cons...
Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may have an anti-SARS-CoV-2 effect. In this study, we constructed a pGL4.10-F2-ACE2 vector with double luciferase genes (firefly and Renilla luciferase) under the control of the ACE2 promoter and used it to screen compounds from Chinese traditional medicinal herbs (CTMHs) that can inhibit ACE2 transcription in human cells. We transfected HEK293T cells with pGL4.10-F2-ACE2 and treated them with CTMH compounds and then measured fluorescence to evaluate the indirect inhibition of ACE2 transcription. Out of 37 compounds tested, andrographolide demonstrated a dose-dependent inhibition of ACE2 transcription. We further confirmed by RT-qPCR and Western blot assays that andrographolide also reduced ACE2 expression in BEAS-2B cells in a dose-dependent manner. Moreover, pseudovirus infection assays in BEAS-2B cells demonstrated that andrographolide can inhibit SARS-CoV-2 infection in a dose-dependent manner. These results suggest that andrographolide has potential anti-SARS-CoV-2 activity and could be a candidate drug for COVID-19 prevention and treatment.
approach to characterize the structure and function of a hypothetical protein of Monkeypox virus exploring Chordopox-A20R domain-containing protein activity.
Hosen MI, Mia ME, Islam MN … +8 more , Khatun MUS, Emon TH, Hossain MA, Akter F, Kader MA, Jeba SH, Faisal A, Miah MA
Antivir Ther · 2024 Jun · PMID 38801671 · Publisher ↗
Monkeypox has emerged as a noteworthy worldwide issue due to its daily escalating case count. This illness presents diverse symptoms, including skin manifestations, which have the potential to spread through contact. The...
Monkeypox has emerged as a noteworthy worldwide issue due to its daily escalating case count. This illness presents diverse symptoms, including skin manifestations, which have the potential to spread through contact. The transmission of this infectious agent is intricate and readily transfers between individuals. The hypothetical protein MPXV-SI-2022V502225_00135 strain of monkeypox underwent structural and functional analysis using NCBI-CD Search, Pfam, and InterProScan. Quality assessment utilized PROCHECK, QMEAN, Verify3D, and ERRAT, followed by protein-ligand docking, visualization, and a 100-nanosecond simulation on Schrodinger Maestro. Different physicochemical properties were estimated, indicating a stable molecular weight (49147.14) and theoretical pI (5.62) with functional annotation tools predicting the target protein to contain the domain of Chordopox_A20R domain. In secondary structure analysis, the helix coil was found to be predominant. The three-dimensional (3D) structure of the protein was obtained using a template protein (PDB ID: ), which became more stable after YASARA energy minimization and was validated by quality assessment tools like PROCHECK, QMEAN, Verify3D, and ERRAT. Protein-ligand docking was conducted using PyRx 9.0 software to examine the binding and interactions between a ligand and a hypothetical protein, focusing on various amino acids. The model structure, active site, and binding site were visualized using the CASTp server, FTsite, and PyMOL. A 100 nanosecond simulation was performed with ligand CID_16124688 to evaluate the efficiency of this protein. The analysis revealed significant binding interactions and enhanced stability, aiding in drug or vaccine design for effective antiviral treatment and patient management.
Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study.
Van Hemelryck S, Van Landuyt E, Hufkens V … +1 more , Vanveggel S
Antivir Ther · 2024 Apr · PMID 38725258 · Publisher ↗
BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplifie...
BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplified protease inhibitor-based ARV regimens. This study assessed the swallowability and acceptability for long-term use of scored placebo tablets matching the D/C/F/TAF FDC tablets in children living with HIV-1. METHODS: This study (NCT04006704) was a Phase 1, open-label, randomized, single-dose, 2-period, 2-sequence crossover study in children living with HIV-1, aged ≥6 to <12 years and weighing ≥25 to <40 kg, on a stable ARV regimen for ≥3 months. Participants were asked to swallow whole (size, 21 × 11 × 7 mm) and split matching placebo D/C/F/TAF tablets. Swallowability of the matching placebo D/C/F/TAF tablets (primary endpoint) was assessed by observers. Acceptability of taking matching placebo D/C/F/TAF tablets and current ARVs was evaluated by participants using a 3-point questionnaire. Participants rated the acceptability for long-term daily use of the placebo D/C/F/TAF tablets, and observers assessed how easily caregivers could split a scored tablet by hand, using 3-point questionnaires. RESULTS: Among the 24 participants who enrolled and completed the study, 95.8% (23/24) were able to swallow the whole and split matching placebo D/C/F/TAF tablets after 1 or 2 attempts. Most participants (>70%) rated the acceptability of tablets for long-term daily use as acceptable or good to take. Breaking the tablets was considered easy or OK by 79.2% (19/24) of caregivers. CONCLUSION: Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04006704.
Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada.
Lepik KJ, Hunt OL, Bacani N … +9 more , Wang L, Harris M, Toy J, McLinden T, Sereda P, Akagi LJ, Ready E, Montaner JS, Barrios R
Antivir Ther · 2024 Feb · PMID 38375582 · Publisher ↗
BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costl...
BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs. METHODS: Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods. RESULTS: During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs. CONCLUSIONS: Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.
Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection.
Boussen I, Salmona M, Sicre De Fontbrune F … +5 more , Xhaard A, De Castro N, Delaugerre C, Chaix ML, Molina JM
Antivir Ther · 2024 Feb · PMID 38353416 · Publisher ↗
We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-C...
We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.
Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA.
Margot N, Pennetzdorfer N, Naik V … +2 more , Rhee M, Callebaut C
Antivir Ther · 2023 Dec · PMID 38085652 · Publisher ↗
BACKGROUND: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug res...
BACKGROUND: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks. METHODS: The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated. Genotypic and phenotypic resistance to LEN was evaluated for subjects with virological failure through Week 52. RESULTS: Overall, viruses with resistance to EIs showed no cross-resistance to LEN, with a mean fold change from wild type close to 1.0. Of the 22 participants analysed for resistance through Week 52, 9 participants (13%) had emergence of capsid resistance mutation(s) while the remaining 13 participants (18%) had no change in the capsid sequence. CONCLUSION: The sequence from EI-resistant isolates did not affect LEN susceptibility. The lack of cross-resistance to LEN across ARV-resistant isolates supports the use of LEN in PWH regardless of their treatment history. During the second half-year period of the CAPELLA Study, development of LEN resistance was rare and was overall associated with functional LEN monotherapy due to either nonadherence or resistance-driven non-susceptibility to OBR.
Dolutegravir and rilpivirine as successful initial antiretroviral therapy in a treatment-naive patient with HIV-1: A case report.
Zafar SJ, Gilliam BL, Schmalzle SA
Antivir Ther · 2023 Dec · PMID 38048138 · Publisher ↗
Abstract loading — click title to view on PubMed.
RVX-208, an inducer of Apolipoprotein A-I, inhibits the particle production of hepatitis B virus through activation of cGAS-STING pathway.
Shu D, Cheng L, Yuan K … +2 more , Liu D, Wei H
Antivir Ther · 2023 Dec · PMID 38037795 · Publisher ↗
BACKGROUND: Previously, we have demonstrated that Apolipoprotein A-I (ApoA-I) could inhibit the secretion of Hepatitis B virus (HBV), suggesting that stimulation of ApoA-I may block particle production. In the present st...
BACKGROUND: Previously, we have demonstrated that Apolipoprotein A-I (ApoA-I) could inhibit the secretion of Hepatitis B virus (HBV), suggesting that stimulation of ApoA-I may block particle production. In the present study, we evaluated the anti-HBV effect of RVX-208, a small-molecule stimulator of ApoA-I gene expression. METHODS: RVX-208 was used to treat HepG2.2.15 cell, a HepG2 derived cell line stably producing HBV virus. Real-time PCR was performed to examine the HBV DNA levels. Magnetic particles, which were coated with anti-HBS or anti-HBE antibody, were used to examine the HBsAg and HBeAg levels in the supernatant of cultured HepG2.2.15 cells in combination with the enzyme conjugates that were prepared with horseradish peroxidase labelled anti-HBS or anti-HBE antibody in a double antibody sandwich manner. RNA-seq, immunoblots and real-time PCR were used to analyze the functional mechanism of RVX-208. RESULTS: RVX-208 could elevate the ApoA-I protein levels in HepG2.2.15 cells. In the meantime, RVX-208 significantly repressed HBV DNA, HBsAg and HBeAg levels in the supernatants of HepG2.2.15 cells. RNA-seq data revealed that RVX-208 treatment not only affected the cholesterol metabolism, which is closely related to ApoA-I, but also regulated signalling pathways that are associated with antiviral immune response. Moreover, mechanistic studies demonstrated that RVX-208 could activate cGAS-STING pathway and upregulate the transcription of a series of interferons, pro-inflammatory cytokines and chemokines with antiviral potential that are at the downstream of cGAS-STING pathway. CONCLUSION: Our study demonstrated that RVX-208, an inducer of ApoA-I, could suppress HBV particle production through activation of cGAS-STING pathway.
Waitlist-controlled trial of an online intervention to address mental health among older people living with HIV.
Berko J, Mazonson P, Short D … +5 more , Karris M, Ehui L, Gutner CA, Spinelli F, Zolopa A
Antivir Ther · 2023 Dec · PMID 38031911 · Publisher ↗
Older people living with HIV (PLWH) often experience elevated levels of depression, anxiety, and loneliness. This waitlist-controlled trial examined the effectiveness of online audio mindfulness lessons in impacting thes...
Older people living with HIV (PLWH) often experience elevated levels of depression, anxiety, and loneliness. This waitlist-controlled trial examined the effectiveness of online audio mindfulness lessons in impacting these feelings among older PLWH. Among 214 participants, the mean (SD) age was 60.4 (5.9) years, 89% were male, and 69% were white. After 25 days, the intervention group showed significant improvements versus the waitlist control group in symptoms of depression (20.3% improvement, < .01) and symptoms of anxiety (22.4% improvement, = .03), but not in loneliness as measured by a Daily Diary (12.9% improvement, = .07) or the 3-Item Loneliness Scale (4.8% improvement, = .27). Secondary analyses among participants with elevated baseline symptoms of depression showed a 26.3% improvement ( < .01), with a moderate effect size (Hedge's g = 0.69). Similarly, those with elevated baseline symptoms of anxiety showed a 25.6% improvement ( < .01), a moderate effect size (g = 0.54), while those with moderate or severely elevated loneliness showed an 18.9% improvement in daily loneliness ( < .01), a moderate effect size (g = 0.55). This waitlist-controlled trial is the first to show that a series of brief, online audio mindfulness lessons improves mental health outcomes among older PLWH. For many patients, this intervention may offer relief that is both accessible and affordable.
Subacute thyroiditis following COVID-19 vaccination: Case presentation.
Tomic AZ, Zafirovic SS, Gluvic ZM … +4 more , Samardzic VS, Macvanin MT, Radunovic ML, Isenovic ER
Antivir Ther · 2023 Oct · PMID 37861754 · Publisher ↗
Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action,...
Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19. The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine. Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal. Data collected during the disease are integral to the medical record. Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition.
Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation.
Shen J, Xu Q, Chen L … +6 more , Chang X, Shen R, Zhao Z, Zhu L, Wu Y, Hou X
Antivir Ther · 2023 Oct · PMID 37846668 · Publisher ↗
BACKGROUND: Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antivir...
BACKGROUND: Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antiviral and anti-inflammatory effects. In this study, APL was evaluated for antiviral activity by its anti-apoptotic, anti-pyroptosis, and anti-inflammatory effects. METHODS: The cytotoxicity of APL was determined by the MTT method. We investigated the therapeutic impact of APL on IBV through a plate assay. We explored that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation in HD11 cells by RT-qPCR and immunofluorescence. Also, it was verified in the clinical chicken embryo trial. RESULTS: We found that APL down-regulated apoptosis-related genes Caspase-3, Caspase-8, Caspase-9, Bax, Bid, and Bak, down-regulated pyroptosis gene DFNA5, and down-regulated inflammation-related genes (NF-κB, NLRP3, iNOS, TNF-α, and IL-1β). In addition, APL reduced the reactive oxygen species (ROS) production in cells. Finally, clinical trials showed that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation, as well as reduced the mortality and malformation of chicken embryos. CONCLUSIONS: In this study, we delved into the antiviral properties of APL in the context of chicken macrophage (HD11) infection with IBV. Our findings confirm that andrographolide effectively inhibits apoptosis, pyroptosis, and inflammation by IBV infection. Furthermore, this inhibition was verified on chicken embryos in vivo. This inhibition suggests a substantial potential for APL as a therapeutic agent to mitigate the harmful effects of IBV on host cells.
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