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The Cochrane Database of Systematic... Jun 2022Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as potential prophylaxis to... (Review)
Review
BACKGROUND
Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as potential prophylaxis to prevent coronavirus disease 2019 (COVID-19).
OBJECTIVES
To assess the effects of SARS-CoV-2-neutralising mAbs, including mAb fragments, to prevent infection with SARS-CoV-2 causing COVID-19; and to maintain the currency of the evidence, using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, and three other databases on 27 April 2022. We checked references, searched citations, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated SARS-CoV-2-neutralising mAbs, including mAb fragments, alone or combined, versus an active comparator, placebo, or no intervention, for pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) of COVID-19. We excluded studies of SARS-CoV-2-neutralising mAbs to treat COVID-19, as these are part of another review.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed search results, extracted data, and assessed risk of bias using Cochrane RoB 2. Prioritised outcomes were infection with SARS-CoV-2, development of clinical COVID-19 symptoms, all-cause mortality, admission to hospital, quality of life, adverse events (AEs), and serious adverse events (SAEs). We rated the certainty of evidence using GRADE.
MAIN RESULTS
We included four RCTs of 9749 participants who were previously uninfected and unvaccinated at baseline. Median age was 42 to 76 years. Around 20% to 77.5% of participants in the PrEP studies and 35% to 100% in the PEP studies had at least one risk factor for severe COVID-19. At baseline, 72.8% to 82.2% were SARS-CoV-2 antibody seronegative. We identified four ongoing studies, and two studies awaiting classification. Pre-exposure prophylaxis Tixagevimab/cilgavimab versus placebo One study evaluated tixagevimab/cilgavimab versus placebo in participants exposed to SARS-CoV-2 wild-type, Alpha, Beta, and Delta variant. About 39.3% of participants were censored for efficacy due to unblinding and 13.8% due to vaccination. Within six months, tixagevimab/cilgavimab probably decreases infection with SARS-CoV-2 (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.29 to 0.70; 4685 participants; moderate-certainty evidence), decreases development of clinical COVID-19 symptoms (RR 0.18, 95% CI 0.09 to 0.35; 5172 participants; high-certainty evidence), and may decrease admission to hospital (RR 0.03, 95% CI 0 to 0.59; 5197 participants; low-certainty evidence). Tixagevimab/cilgavimab may result in little to no difference on mortality within six months, all-grade AEs, and SAEs (low-certainty evidence). Quality of life was not reported. Casirivimab/imdevimab versus placebo One study evaluated casirivimab/imdevimab versus placebo in participants who may have been exposed to SARS-CoV-2 wild-type, Alpha, and Delta variant. About 36.5% of participants opted for SARS-CoV-2 vaccination and had a mean of 66.1 days between last dose of intervention and vaccination. Within six months, casirivimab/imdevimab may decrease infection with SARS-CoV-2 (RR 0.01, 95% CI 0 to 0.14; 825 seronegative participants; low-certainty evidence) and may decrease development of clinical COVID-19 symptoms (RR 0.02, 95% CI 0 to 0.27; 969 participants; low-certainty evidence). We are uncertain whether casirivimab/imdevimab affects mortality regardless of the SARS-CoV-2 antibody serostatus. Casirivimab/imdevimab may increase all-grade AEs slightly (RR 1.14, 95% CI 0.98 to 1.31; 969 participants; low-certainty evidence). The evidence is very uncertain about the effects on grade 3 to 4 AEs and SAEs within six months. Admission to hospital and quality of life were not reported. Postexposure prophylaxis Bamlanivimab versus placebo One study evaluated bamlanivimab versus placebo in participants who may have been exposed to SARS-CoV-2 wild-type. Bamlanivimab probably decreases infection with SARS-CoV-2 versus placebo by day 29 (RR 0.76, 95% CI 0.59 to 0.98; 966 participants; moderate-certainty evidence), may result in little to no difference on all-cause mortality by day 60 (R 0.83, 95% CI 0.25 to 2.70; 966 participants; low-certainty evidence), may increase all-grade AEs by week eight (RR 1.12, 95% CI 0.86 to 1.46; 966 participants; low-certainty evidence), and may increase slightly SAEs (RR 1.46, 95% CI 0.73 to 2.91; 966 participants; low-certainty evidence). Development of clinical COVID-19 symptoms, admission to hospital within 30 days, and quality of life were not reported. Casirivimab/imdevimab versus placebo One study evaluated casirivimab/imdevimab versus placebo in participants who may have been exposed to SARS-CoV-2 wild-type, Alpha, and potentially, but less likely to Delta variant. Within 30 days, casirivimab/imdevimab decreases infection with SARS-CoV-2 (RR 0.34, 95% CI 0.23 to 0.48; 1505 participants; high-certainty evidence), development of clinical COVID-19 symptoms (broad-term definition) (RR 0.19, 95% CI 0.10 to 0.35; 1505 participants; high-certainty evidence), may result in little to no difference on mortality (RR 3.00, 95% CI 0.12 to 73.43; 1505 participants; low-certainty evidence), and may result in little to no difference in admission to hospital. Casirivimab/imdevimab may slightly decrease grade 3 to 4 AEs (RR 0.50, 95% CI 0.24 to 1.02; 2617 participants; low-certainty evidence), decreases all-grade AEs (RR 0.70, 95% CI 0.61 to 0.80; 2617 participants; high-certainty evidence), and may result in little to no difference on SAEs in participants regardless of SARS-CoV-2 antibody serostatus. Quality of life was not reported.
AUTHORS' CONCLUSIONS
For PrEP, there is a decrease in development of clinical COVID-19 symptoms (high certainty), infection with SARS-CoV-2 (moderate certainty), and admission to hospital (low certainty) with tixagevimab/cilgavimab. There is low certainty of a decrease in infection with SARS-CoV-2, and development of clinical COVID-19 symptoms; and a higher rate for all-grade AEs with casirivimab/imdevimab. For PEP, there is moderate certainty of a decrease in infection with SARS-CoV-2 and low certainty for a higher rate for all-grade AEs with bamlanivimab. There is high certainty of a decrease in infection with SARS-CoV-2, development of clinical COVID-19 symptoms, and a higher rate for all-grade AEs with casirivimab/imdevimab. Although there is high-to-moderate certainty evidence for some outcomes, it is insufficient to draw meaningful conclusions. These findings only apply to people unvaccinated against COVID-19. They are only applicable to the variants prevailing during the study and not other variants (e.g. Omicron). In vitro, tixagevimab/cilgavimab is effective against Omicron, but there are no clinical data. Bamlanivimab and casirivimab/imdevimab are ineffective against Omicron in vitro. Further studies are needed and publication of four ongoing studies may resolve the uncertainties.
Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Antineoplastic Agents, Immunological; COVID-19; Humans; Middle Aged; SARS-CoV-2
PubMed: 35713300
DOI: 10.1002/14651858.CD014945.pub2 -
Clinical Lymphoma, Myeloma & Leukemia Oct 2020Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow failure, increased risk of progression to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow failure, increased risk of progression to acute myeloid leukemia, and constitutional symptoms. For over 3 decades, various formulations of interferon (IFN) have been used for the treatment of MF, with variable results, and the role of IFN in the treatment of MF is evolving.
PATIENTS AND METHODS
For this systematic review and meta-analysis, Medline and Embase via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from inception through March 2019 for studies of pegylated IFN (peg-IFN) and non-peg-IFN in MF patients. The primary outcome of overall response rate was defined as a composite of complete response, partial response, complete hematologic response, and partial hematologic response. Random-effects models were used to pool overall response rate, and metaregression analyses were performed to compare peg-IFN and non--peg-IFN formulations.
RESULTS
Among the 10 studies with 141 MF patients included, the overall response rate was 49.9% (95% confidence interval [CI], 30.4-69.3), and there was no statistically significant difference (P = .99) between peg-IFN (50.0%; 95% CI, 26.2-73.9; I = 76.9%) and non-peg-IFN (49.6%; 95% CI, 20.5-79.0; I = 56.7%). Treatment discontinuation resulting from adverse events was common with non-peg-IFN at 35.8% (95% CI, 3.5-68.1) per year, and less in the one study on peg-IFN (0.5% per year).
CONCLUSION
IFN can lead to hematologic improvements in a subset of MF patients, but study quality is limited and heterogenous. Biomarkers predicting response to IFN and formulations with improved tolerability are needed.
Topics: Humans; Interferon-alpha; Primary Myelofibrosis
PubMed: 32669244
DOI: 10.1016/j.clml.2020.05.018 -
BMC Infectious Diseases Aug 2014Few data are available on antiretroviral therapy (ART) response among HIV-2 infected patients. We conducted a systematic review on treatment outcomes among HIV-2... (Review)
Review
BACKGROUND
Few data are available on antiretroviral therapy (ART) response among HIV-2 infected patients. We conducted a systematic review on treatment outcomes among HIV-2 infected patients on ART, focusing on the immunological and virological responses in adults.
METHODS
Data were extracted from articles that were selected after screening of PubMed/MEDLINE up to November 2012 and abstracts of the 1996-2012 international conferences. Observational cohorts, clinical trials and program reports were eligible as long as they reported data on ART response (clinical, immunological or virological) among HIV-2 infected patients. The determinants investigated included patients' demographic characteristics, CD4 cell count at baseline and ART received.
RESULTS
Seventeen reports (involving 976 HIV-2 only and 454 HIV1&2 dually reactive patients) were included in the final review, and the analysis presented in this report are related to HIV-2 infected patients only. There was no randomized controlled trial and only two cohorts had enrolled more than 100 HIV-2 only infected patients. The median CD4 count at ART initiation was 165 cells/mm3, [IQR; 137-201] and the median age at ART initiation was 44 years (IQR: 42-48 years). Ten studies included 103 patients treated with three nucleoside reverse transcriptase inhibitors (NRTI). Protease inhibitor (PI) based regimens were reported by 16 studies. Before 2009, the most frequent PIs used were Nelfinavir and Indinavir, whereas it was Lopinavir/ritonavir thereafter. The immunological response at month-12 was reported in six studies and the mean CD4 cell count increase was +118 cells/μL (min-max: 45-200 cells/μL).
CONCLUSION
Overall, clinical and immuno-virologic outcomes in HIV-2 infected individuals treated with ART are suboptimal. There is a need of randomized controlled trials to improve the management and outcomes of people living with HIV-2 infection.
Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Retroviral Agents; CD4 Lymphocyte Count; Clinical Trials as Topic; Female; HIV Infections; HIV-2; Humans; Indinavir; Lopinavir; Male; Middle Aged; Nelfinavir; Ritonavir; Treatment Outcome
PubMed: 25154616
DOI: 10.1186/1471-2334-14-461 -
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
Value in Health : the Journal of the... Dec 2023This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and... (Meta-Analysis)
Meta-Analysis
Comparative Efficacy of Venetoclax-Based Combination Therapies and Other Therapies in Treatment-Naive Patients With Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy: A Network Meta-Analysis.
OBJECTIVES
This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and decitabine monotherapies and best supportive care (BSC) in adults with untreated acute myeloid leukemia ineligible for intensive chemotherapy.
METHODS
A systematic literature review and feasibility assessment was conducted to select phase III randomized controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs) with higher values indicating a higher likelihood of being effective.
RESULTS
A total of 1140 patients across 5 trials were included. VEN + LDAC (SUCRA 91.4%) and VEN + AZA (87.5%) were the highest ranked treatments for complete remission + complete remission with incomplete blood count recovery. VEN + LDAC was associated significantly higher response rates versus AZA (odds ratio 5.64), LDAC (6.39), and BSC (23.28). VEN + AZA was also associated significantly higher response rates than AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN + AZA (SUCRA: 95.2%) and VEN + LDAC (75.9%) were the highest ranked treatments. VEN + AZA was associated with significant improvements in OS compared with AZA (hazard ratio 0.66), LDAC (0.57), and BSC (0.37), and VEN + LDAC was associated with significant improvements in OS compared with LDAC (0.70) and BSC (0.46).
CONCLUSIONS
VEN + AZA and VEN + LDAC demonstrated improved efficacy compared with alternative therapies among treatment-naive patients with acute myeloid leukemia ineligible for intensive chemotherapy.
Topics: Adult; Humans; Treatment Outcome; Azacitidine; Network Meta-Analysis; Bayes Theorem; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Leukemia, Myeloid, Acute
PubMed: 37741447
DOI: 10.1016/j.jval.2023.09.001 -
Liver International : Official Journal... Mar 2024We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines.
METHODS
We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach.
RESULTS
A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%).
CONCLUSIONS
All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes.
PROSPERO RECORD
CRD42020146752.
Topics: Adult; Child; Adolescent; Humans; Child, Preschool; Sofosbuvir; Hepatitis C, Chronic; Antiviral Agents; Hepatitis C; Sustained Virologic Response; Hepacivirus; Drug Therapy, Combination; Genotype; Treatment Outcome; Carbamates; Imidazoles; Pyrrolidines; Valine
PubMed: 38293756
DOI: 10.1111/liv.15827 -
Alimentary Pharmacology & Therapeutics Mar 2019Hepatitis C virus (HCV) genotype 6 (GT6) is predominantly encountered in Southeast Asia and data on GT6 response to direct-acting antiviral (DAA) therapy are relatively...
BACKGROUND
Hepatitis C virus (HCV) genotype 6 (GT6) is predominantly encountered in Southeast Asia and data on GT6 response to direct-acting antiviral (DAA) therapy are relatively limited.
AIM
To review the epidemiology and virologic outcome of DAA regimens in HCV GT6 patients.
METHODS
Electronic literature search of PubMed, EMBASE, and The Cochrane Library databases were conducted.
RESULTS
Hepatitis C virus genotype 6 is the most genetically diverse, has a prevalence of 19.9%-95.6% in HCV infected patients in Southeast Asia and has been associated with a higher risk of HCC in those with cirrhosis. After an extensive literature review, a total of 20 studies were selected to assess study population and treatment outcomes (total of 938 GT6 patients were included); 12 were clinical trials and eight were observational studies. Sustained virologic response at week 12 (SVR 12) following glecaprevir/pibrentasvir (n = 4; 108 patients), ledipasvir/sofosbuvir (n = 8; 427 patients), sofosbuvir/velpatasvir with or without voxilaprevir (n = 5; 171 patients), sofosbuvir/daclatasvir (n = 3; 172 patients) and sofosbuvir with ribavirin (n = 3; 60 patients) was 98%-100%, 64%-100%, 100%, 88%-94% and 100%, respectively. Failure was mostly in those with cirrhosis and prior treatment experience. DAA therapy was well tolerated and with a serious adverse event rate of <5%.
CONCLUSIONS
Hepatitis C virus genotype 6 is genetically diverse and is highly prevalent in Asia. While SVR rates have been high, cirrhosis and prior treatment experience marginally compromise response to DAAs. Large scale and exclusive studies in HCV genotype 6 prevalent areas are needed, while the current evidence suggests that DAAs are highly effective and safe.
Topics: Antiviral Agents; Asia; Clinical Trials as Topic; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Multicenter Studies as Topic; Observational Studies as Topic; Sustained Virologic Response
PubMed: 30687952
DOI: 10.1111/apt.15100 -
Pathogens (Basel, Switzerland) Nov 2023Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants... (Review)
Review
Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants (SNVs). and genes have been associated with severe COVID-19 in populations from the United Kingdom, Africa, and Latin America. IFNAR1 and IFNAR2 are subunits forming the type I interferon receptor (IFNAR). SNVs in the genes impact protein function, affecting antiviral response and disease phenotypes. This systematic review aimed to describe and variants associated with COVID-19 susceptibility and severity. Accordingly, the current review focused on and studies published between January 2021 and February 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. The electronic search was conducted in PubMed databases using Boolean operators and inclusion and exclusion criteria. Of the 170 literature pieces, 11 studies were included. We include case reports of rare SNVs, defined by minor allele frequency (MAF) < 1%, and genome-wide associated studies (GWAS). Variants in and could potentially be new targets for therapies that limit the infection and the resulting inflammation by SARS-CoV-2 infection.
PubMed: 38003785
DOI: 10.3390/pathogens12111320 -
Frontiers in Immunology 2021Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resulting in a range of clinical manifestations... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resulting in a range of clinical manifestations and outcomes. Laboratory and immunological alterations have been considered as potential markers of disease severity and clinical evolution. Type I interferons (IFN-I), mainly represented by IFN-α and β, are a group of cytokines with an important function in antiviral responses and have played a complex role in COVID-19. Some studies have demonstrated that IFN-I levels and interferon response is elevated in mild cases, while other studies have noted this in severe cases. The involvement of IFN-I on the pathogenesis and outcomes of SARS-CoV-2 infection remains unclear. In this study, we summarize the available evidence of the association of plasma protein levels of type I IFN with the severity of COVID-19.
METHODS
The PRISMA checklist guided the reporting of the data. A systematic search of the MEDLINE (PubMed), EMBASE, and Web of Science databases was performed up to March of 2021, looking for articles that evaluated plasma protein levels of IFN-I in mild, severe, or critical COVID-19 patients. Comparative meta-analyses with random effects were performed to compare the standardized mean differences in plasma protein levels of IFN-I of mild versus severe and mild versus critical patients. Meta-regressions were performed to test the moderating role of age, sex, time that the IFN-I was measured, and limit of detection of the assay used in the difference between the means.
RESULTS
There was no significant difference in plasma levels of IFN-α when comparing between mild and severe patients (SMD = -0.236, 95% CI -0.645 to 0.173, p = 0.258, I2 = 82.11), nor when comparing between patients mild and critical (SMD = 0.203, 95% CI -0.363 to 0.770, p = 0.481, I2 = 64.06). However, there was a significant difference between healthy individuals and patients with mild disease (SMD = 0.447, 95% CI 0.085 to 0.810, p = 0.016, I2 = 62.89).
CONCLUSIONS
Peripheral IFN-α cannot be used as a severity marker as it does not determine the clinical status presented by COVID-19 patients.
Topics: Biomarkers; COVID-19; Disease Progression; Humans; Interferon Type I; SARS-CoV-2; Severity of Illness Index
PubMed: 34054820
DOI: 10.3389/fimmu.2021.657363 -
Journal of Cancer 2022Immune checkpoint inhibitor (ICI) therapy is now administered to patients with advanced cancers. However, the safety and efficacy of ICIs in cancer patients with... (Review)
Review
Immune checkpoint inhibitor (ICI) therapy is now administered to patients with advanced cancers. However, the safety and efficacy of ICIs in cancer patients with hepatitis B virus (HBV) infection is unknown. Therefore, we performed this systematic review to examine the safety and efficacy of ICIs in patients with HBV infection, with particular focus on HBV reactivation. Studies examining ICI treatment in patients with advanced cancer and HBV infection in PubMed from database inception to April 2022 were retrieved in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, reports of individuals diagnosed with HBV reactivation were supplemented through the Food and Drug Administration Adverse Event Reporting System. We identified 20 articles (8 case reports, 10 retrospective case series, and 2 prospective clinical trials) and 2 meeting abstracts including 633 patients with advanced cancer and HBV infection treated with ICIs. The overall rate of HBV reactivation was 4.1% (26/633), and no HBV-related fatal events were reported. Among patients with HBV reactivation with known baseline data (20/26), HBV-DNA returned to undetectable status in 15 of 17 patients (88.2%) after a median 5.5 weeks (range, 1-14 weeks). Therapeutic responses to ICIs were observed in 14 of 88 patients (15.91%) with hepatocellular carcinoma, 6 of 45 patients (13.33%) with non-small cell lung cancer, and 3 of 13 patients (23.08%) with melanoma. ICIs may be safe and effective in patients with advanced cancer and HBV infection. However, there is still a need for clinical monitoring of liver enzymes and HBV-DNA during ICI therapy. Prospective trials are necessary to elucidate the appropriate antiviral therapy in these patients.
PubMed: 36484006
DOI: 10.7150/jca.77247