ABSTRACT
This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.
Subject(s)
Antiviral Agents , Hepatitis B virus , Hepatitis B, Chronic , Tenofovir , Humans , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Tenofovir/therapeutic use , Tenofovir/analogs & derivatives , Tenofovir/adverse effects , Hepatitis B virus/drug effects , Treatment Outcome , Virus Replication/drug effects , Adenine/analogs & derivatives , Adenine/therapeutic use , Adenine/adverse effects , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/adverse effectsABSTRACT
BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.
Subject(s)
Antiviral Agents , Drug Therapy, Combination , Hepatitis B, Chronic , Interferon-alpha , Polyethylene Glycols , Recombinant Proteins , Tenofovir , Humans , Tenofovir/therapeutic use , Tenofovir/administration & dosage , Tenofovir/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Male , Female , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/administration & dosage , Child , Recombinant Proteins/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Polyethylene Glycols/therapeutic use , Polyethylene Glycols/adverse effects , Polyethylene Glycols/administration & dosage , Interferon-alpha/therapeutic use , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Child, Preschool , Treatment Outcome , Interferon alpha-2/therapeutic use , Interferon alpha-2/administration & dosage , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B virus/drug effects , DNA, Viral/blood , Alanine/therapeutic use , Alanine/analogs & derivativesABSTRACT
BACKGROUND: A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. METHODS: We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. RESULTS: Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23-0.67], p < 0.001) than no treatment. All-cause mortality at 28 days was numerically lower among remdesivir-treated patients (0.1% vs. 0.4%; aOR 0.32 [95% CI 0.03-1.40]). Similar benefit of RDV treatment on 28-day all-cause hospitalization was observed across Omicron periods, aOR (95% CI): BA.2/BA2.12.1 (0.77[0.19-2.41]), BA.4/5 (0.50[95% CI 0.50-1.01]), BQ.1/BQ.1.1/XBB.1.5 (0.21[95% CI 0.08-0.57]. CONCLUSION: Among outpatients with SARS-CoV-2 during recent Omicron surges, remdesivir was associated with lower hospitalization than no treatment, supporting current National Institutes of Health Guidelines.
Subject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Hospitalization , Outpatients , SARS-CoV-2 , Humans , Alanine/analogs & derivatives , Alanine/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Male , Female , Middle Aged , Retrospective Studies , Antiviral Agents/therapeutic use , COVID-19/mortality , Hospitalization/statistics & numerical data , SARS-CoV-2/drug effects , Aged , Outpatients/statistics & numerical data , Adult , Colorado , Treatment OutcomeABSTRACT
INTRODUCTION: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). METHODS: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase-3 trial clinical trial in South Africa (study dates: January 2017-February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment-emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment-emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). RESULTS: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0-3.4), -0.5 mmHg (95% CI: -2.2 to 1.7) and -2.1 mmHg (95% CI: -3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4-22.9), 15.4% (95% CI: 11.0-19.9) and 13.3% (95% CI: 8.9-17.6) of participants developed treatment-emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment-emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. CONCLUSIONS: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. CLINICAL TRIAL NUMBER: NCT03122262.
Subject(s)
Blood Pressure , HIV Infections , Hypertension , Tenofovir , Weight Gain , Humans , Male , Female , South Africa , HIV Infections/drug therapy , Adult , Middle Aged , Tenofovir/therapeutic use , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Weight Gain/drug effects , Hypertension/drug therapy , Blood Pressure/drug effects , Blood Pressure/physiology , Pyridones/therapeutic use , Piperazines/therapeutic use , Oxazines/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Glomerular Filtration Rate/drug effects , Alanine/therapeutic use , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effectsABSTRACT
BACKGROUND: The rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis. METHODS: Adults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls. RESULTS: All Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA. CONCLUSIONS: RSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.
Subject(s)
Anti-HIV Agents , Emtricitabine , HIV Infections , Tenofovir , Humans , HIV Infections/drug therapy , Pilot Projects , Male , Female , Adult , Tenofovir/therapeutic use , Tenofovir/administration & dosage , Tenofovir/analogs & derivatives , Middle Aged , Anti-HIV Agents/therapeutic use , Emtricitabine/therapeutic use , Emtricitabine/administration & dosage , Alanine/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , HIV-1/drug effects , Piperazines/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Viral Load/drug effects , Amides/therapeutic use , RNA, Viral/blood , PyridonesABSTRACT
INTRODUCTION: The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. MATERIALS AND METHODS: The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 â patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 â patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. RESULTS: There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. CONCLUSION: This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV Reverse Transcriptase , HIV-1 , Mutation , Tenofovir , Humans , Tenofovir/therapeutic use , Tenofovir/analogs & derivatives , HIV Infections/drug therapy , HIV Infections/virology , HIV Infections/genetics , HIV Reverse Transcriptase/genetics , HIV-1/genetics , HIV-1/drug effects , Male , Female , Adult , Anti-HIV Agents/therapeutic use , Middle Aged , Drug Resistance, Viral/genetics , Amino Acid Substitution , Alanine/therapeutic use , Russia/epidemiology , Adenine/analogs & derivatives , Adenine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load/drug effectsABSTRACT
Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.
Subject(s)
Azetidines , COVID-19 Drug Treatment , COVID-19 , Drug Therapy, Combination , Intensive Care Units , Methylprednisolone , Purines , Pyrazoles , SARS-CoV-2 , Sulfonamides , Humans , Purines/therapeutic use , Purines/administration & dosage , Male , Female , Azetidines/therapeutic use , Azetidines/administration & dosage , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Middle Aged , Aged , Retrospective Studies , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , COVID-19/mortality , COVID-19/complications , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/administration & dosage , Treatment Outcome , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/administration & dosageABSTRACT
BACKGROUND: There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients. METHODS: The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patient's medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured. RESULTS: Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisher's exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications. CONCLUSION: Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications.
Subject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Humans , Male , Alanine/analogs & derivatives , Alanine/adverse effects , Alanine/therapeutic use , Female , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Middle Aged , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Case-Control Studies , Aged , COVID-19/complications , Adult , SARS-CoV-2 , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Sex Factors , Bradycardia/chemically induced , Bradycardia/epidemiology , Retrospective StudiesABSTRACT
Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0-3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, Pâ =â .03). Delaying remdesivir treatmentâ ≥â 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18-32.44; Pâ =â .03) and Charlson comorbidity indexâ ≥â 3 (aOR, 9.62; 95% CI, 1.65-56.10; Pâ =â .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.
Subject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 Drug Treatment , SARS-CoV-2 , Severity of Illness Index , Humans , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/administration & dosage , Male , Female , Retrospective Studies , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Middle Aged , Republic of Korea , Aged , Treatment Outcome , COVID-19 , Hospitalization , Time-to-Treatment , Time Factors , Disease ProgressionABSTRACT
A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80- < 90%, and < 80% groups, respectively. Across all PDC groups, more than 90% of patients who received B/F/TAF were receiving treatment at 1 year. There was no significant difference in the risk of discontinuation between the lower PDC groups (80- < 90% and < 80%) and the PDC ≥ 90% group (0.400 [0.096, 1.661]; 2.244 [0.663, 7.594], hazard ratio [95% confidence interval], respectively). A drug resistance test was implemented for 15 patients, none of whom discontinued B/F/TAF after the test. The results suggest that events that could cause discontinuation, such as virologic failure, were not associated with PDC.
Subject(s)
Alanine , Anti-HIV Agents , Emtricitabine , HIV Infections , Medication Adherence , Pyridones , Tenofovir , Humans , Tenofovir/therapeutic use , Tenofovir/analogs & derivatives , Male , Female , HIV Infections/drug therapy , HIV Infections/virology , Emtricitabine/therapeutic use , Japan , Middle Aged , Retrospective Studies , Adult , Anti-HIV Agents/therapeutic use , Alanine/therapeutic use , Alanine/analogs & derivatives , Pyridones/therapeutic use , Piperazines/therapeutic use , Treatment Outcome , Amides/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Adenine/analogs & derivatives , Adenine/therapeutic use , Databases, Factual , Drug CombinationsABSTRACT
DA-9601 extracted from Artemisia asiatica contains a bioactive compound - eupatilin - that can protect against gastric mucosal damage through anti-inflammatory and anti-oxidative properties and is approved for treating acute and chronic gastritis in Korea, but their ability to protect gastrointestinal (GI) bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is unclear. We aimed to compare the protective effects of DA-9601 to those of proton pump inhibitors (PPI) and rebamipide against upper and lower GI bleeding in patients with rheumatoid arthritis (RA) undergoing long-term NSAIDs therapy using the Korean Health Insurance Review and Assessment database. In this nationwide retrospective cohort study, we evaluated patients with RA who concurrently received NSAIDs for >3 months with DA-9601, PPI, or rebamipide between January 2015 and December 2017. The index date was the date of NSAIDs initiation, and all patients were followed up until December 2020 to detect upper and lower GI bleeding. In total, 24,258 patients with RA were eligible, and 5468 (22.5%), 4417 (18.2%), and 14,373 (59.3%) received DA-9601, PPI, or rebamipide, respectively, on the index date. During follow-up, upper and lower GI bleeding occurred in 508 (2.1%) and 402 (1.6%) patients with RA, respectively. The incidence rate of upper and lower GI bleeding was 615/100,000 and 485/100,000 person-years, respectively. Among patients with RA receiving DA-9601, PPI, or rebamipide, the frequencies of NSAIDs-induced upper GI bleeding were 0.5%, 0.4%, and 1.2%, respectively. The frequencies of NSAIDs-induced lower GI bleeding were 0.4%, 0.4%, and 0.9%, respectively. The incidence of NSAIDs-induced upper GI bleeding in patients with RA receiving DA-9601, PPI, and rebamipide was 601/100,000, 705/100,000, and 596/100,000 person-years, respectively, while the incidence of NSAIDs-induced lower GI bleeding in the same groups was 449/100,000, 608/100,000, and 465/100,000 person-years, respectively. In the multivariate Cox regression analysis, no significant difference was observed in lower and upper GI bleeding hazards between patients with RA using DA-9601, PPI, and rebamipide. Our results suggest that DA-9601 may exhibit protection against NSAIDs-induced GI bleeding that is comparable to those of PPI and rebamipide in patients with RA.
Subject(s)
Alanine , Anti-Inflammatory Agents, Non-Steroidal , Arthritis, Rheumatoid , Gastrointestinal Hemorrhage , Proton Pump Inhibitors , Quinolones , Humans , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/complications , Female , Male , Middle Aged , Republic of Korea/epidemiology , Alanine/analogs & derivatives , Alanine/therapeutic use , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/prevention & control , Proton Pump Inhibitors/therapeutic use , Retrospective Studies , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Quinolones/therapeutic use , Quinolones/adverse effects , Aged , AdultSubject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , SARS-CoV-2 , Viral Load , Humans , Alanine/analogs & derivatives , Alanine/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Antiviral Agents/therapeutic use , SARS-CoV-2/drug effects , Male , Middle Aged , Viral Load/drug effects , COVID-19/virology , Female , Aged , AdultABSTRACT
Fibrotic skin diseases, such as keloids, are pathological results of aberrant tissue healing and are characterized by overgrowth of dermal fibroblasts. Remdesivir (RD), an antiviral drug, has been reported to have pharmacological activities in a wide range of fibrotic diseases. However, whether RD function on skin fibrosis remains unclear. Therefore, in our study, we explored the potential effect and mechanisms of RD on skin fibrosis both in vivo and in vitro. As expected, the results demonstrated that RD alleviated BLM-induced skin fibrosis and attenuates the gross weight of keloid tissues in vivo. Further studies suggested that RD suppressed fibroblast activation and autophagy both in vivo and in vitro. In addition, mechanistic research showed that RD attenuated fibroblasts activation by the TGF-ß1/Smad signaling pathway and inhibited fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. In summary, our results demonstrate therapeutic potential of RD for skin fibrosis in the future.
Subject(s)
Adenosine Monophosphate , Alanine , Fibroblasts , Fibrosis , Signal Transduction , Skin , Transforming Growth Factor beta1 , Animals , Signal Transduction/drug effects , Transforming Growth Factor beta1/metabolism , Fibrosis/drug therapy , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Fibroblasts/drug effects , Fibroblasts/metabolism , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/metabolism , Mice , Skin/drug effects , Skin/pathology , Skin/metabolism , Humans , Autophagy/drug effects , Keloid/drug therapy , Keloid/metabolism , Keloid/pathology , Antiviral Agents/pharmacology , TOR Serine-Threonine Kinases/metabolism , Bleomycin , Phosphatidylinositol 3-Kinases/metabolism , Male , Proto-Oncogene Proteins c-akt/metabolism , Smad Proteins/metabolismABSTRACT
Among immunocompromised hosts, leukemia patients, and hematopoietic cell transplant recipients are particularly vulnerable, facing challenges in balancing coronavirus disease 2019 (COVID-19) management with their underlying conditions. In this How I Treat article, we discuss how we approach severe acute respiratory syndrome coronavirus 2 infections in daily clinical practice, considering the existing body of literature and for topics where the available data are not sufficient to provide adequate guidance, we provide our opinion based on our clinical expertise and experience. Diagnostic approaches include nasopharyngeal swabs for polymerase chain reaction testing and chest computed tomography scans for symptomatic patients at risk of disease progression. Preventive measures involve strict infection control protocols and prioritizing vaccination for both patients and their families. Decisions regarding chemotherapy or hematopoietic cell transplantation in leukemia patients with COVID-19 require careful consideration of factors such as COVID-19 severity and treatment urgency. Treatment protocols include early initiation of antiviral therapy, with nirmatrelvir/ritonavir or remdesivir. For cases of prolonged viral shedding, distinguishing between viable and non-viable viruses remains challenging but is crucial for determining contagiousness and guiding management decisions. Overall, individualized approaches considering immune status, clinical presentation, and viral kinetics are essential for effectively managing COVID-19 in leukemia patients.
Subject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 , Hematopoietic Stem Cell Transplantation , Immunocompromised Host , Leukemia , SARS-CoV-2 , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , COVID-19/complications , Antiviral Agents/therapeutic use , Leukemia/complications , Leukemia/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , COVID-19 Drug Treatment , Ritonavir/therapeutic use , Transplant Recipients , Lopinavir/therapeutic use , Virus Shedding , Drug CombinationsABSTRACT
(1) Background: Geriatric patients are at high risk of complications of Coronavirus disease-2019 (COVID-19) and are good candidates for antiviral drugs. (2) Methods: A retrospective study of electronic health records (EHRs) aiming to describe antiviral (nirmatrelvir and ritonavir (nirmatrelvir/r) or remdesivir) use, drug-drug interactions (DDIs) and adverse drug reactions (ADRs) in elderly patients (75 and over), hospitalized with mild-to-moderate COVID-19 between July 2022 and June 2023. (3) Results: Out of 491 patients (mean age: 86.9 years), 180 (36.7%) received nirmatrelvir/r, 78 (15.9%) received remdesivir, and 233 (47.4%) received no antiviral therapy. No association was found between the choice of antiviral and the demographic or medical data. No serious ADR was observed. Nirmatrelvir/r dosage adjustment was inadequate in 65% of patients with renal impairment. In total, 128 patients (71%) on nirmatrelvir/r had potential pharmacokinetic DDIs, with 43 resulting in a possibly related ADR. In the remdesivir group, pharmacodynamic DDIs were more frequent, with QTc prolongation risk in 56 patients (72%). Only 20 patients underwent follow-up ECG, revealing QTc prolongation in 4. (4) Conclusions: There is an underutilization of antivirals despite their justified indications. Nirmatrelvir/r dosage was rarely adjusted to renal function. Dose adjustments and closer monitoring are needed due to the high risk of drug interactions.
Subject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 Drug Treatment , Drug Interactions , Ritonavir , SARS-CoV-2 , Humans , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Female , Male , Aged, 80 and over , Retrospective Studies , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/adverse effects , SARS-CoV-2/drug effects , Aged , Ritonavir/therapeutic use , Ritonavir/adverse effects , COVID-19/virology , Adenosine/analogs & derivativesABSTRACT
BACKGROUND SARS-CoV-2 infection can persist in immunocompromised patients with hematological malignancies, despite antiviral treatment. This report is of a 67-year-old man with chronic lymphocytic leukemia (CLL), secondary hypogammaglobulinemia, and thrombocytopenia on maintenance therapy with ibrutinib, with persistent SARS-CoV-2 infection unresponsive to antiviral treatment, including remdesivir, nirmatrelvir/ritonavir (Paxlovid), and tixagevimab/cilgavimab (Evusheld). CASE REPORT The patient was admitted to our hospital 3 times. During his first hospitalization, he was treated with 5-day course of remdesivir and intravenous steroids; however, antigen and molecular nasopharyngeal swabs were persistently positive, and he was discharged home. Due to respiratory worsening, he was rehospitalized, and despite being treated initially with tixagevimab/cilgavimab, and subsequently with a remdesivir course of 5 days, SARS-CoV-2 tests remained persistently positive. During his third hospital stay, our patient was subjected to combined therapy with remdesivir and nirmatrelvir/ritonavir for 5 days, obtaining a significant reduction of viral load at both antigen and molecular testing. As an ultimate attempt to achieve a negative status before discharge, a 10-day course of combined remdesivir and nirmatrelvir/ritonavir was administered, with a temporary reduction of viral load, followed by a sudden increase immediately after the discontinuation of Paxlovid. Due to worsening hematological disease and bacterial over-infections, the patient gradually worsened until death. CONCLUSIONS This is an emblematic case of correlation between persistent SARS-CoV-2 infection and immunosuppression status in hematological hosts. In these patients, the viral load remains high, favoring the evolution of the virus, and the immunodeficiency makes it difficult to identify the appropriate therapeutic approach.
Subject(s)
Adenine , COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Piperidines , Humans , Male , Aged , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Adenine/analogs & derivatives , Adenine/therapeutic use , COVID-19/diagnosis , Piperidines/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Immunocompromised Host , Maintenance ChemotherapyABSTRACT
BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.
Subject(s)
Acute Kidney Injury , Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 Drug Treatment , Glomerular Filtration Rate , Hospital Mortality , Hospitalization , SARS-CoV-2 , Humans , Alanine/analogs & derivatives , Alanine/therapeutic use , Alanine/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/adverse effects , Male , Female , Retrospective Studies , Middle Aged , Aged , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Hospitalization/statistics & numerical data , COVID-19/complications , COVID-19/mortality , Treatment Outcome , Renal Insufficiency/epidemiology , Bradycardia/chemically induced , Bradycardia/epidemiology , AdultABSTRACT
BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).