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Clinical Gastroenterology and... Jan 2018We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in patients with hepatitis C virus infection who achieved a sustained virologic response (SVR).
METHODS
We searched the literature through October 2016 for observational studies or randomized controlled trials of adults with hepatitis C virus infection who received antiviral therapy (either direct-acting antiviral agents or interferon-based therapies), underwent liver stiffness measurement using VCTE before starting therapy, and had at least 1 follow-up VCTE after completion of therapy; studies also provided data on mean or median liver stiffness measurements for patients who did and did not achieve an SVR. We identified 24 studies, and estimated weighted mean difference (and 95% confidence interval) in liver stiffness in patients with versus without SVR using random-effects meta-analysis.
RESULTS
In patients who achieved SVR, liver stiffness decreased by 2.4 kPa at the end of therapy (95% CI, -1.7 to -3.0), by 3.1 kPa 1-6 months after therapy (95% CI, -1.6 to -4.7), by 3.2 kPa 6-12 months after therapy (90% CI, -2.6 to -3.9), and 4.1 kPa 12 months or more after therapy (95% CI, -3.3 to -4.9) (median decrease, 28.2%; interquartile range, 21.8-34.8). In contrast, there was no significant change in liver stiffness in patients who did not achieve an SVR (at 6-12 months after therapy, decrease of 0.6 kPa; 95% CI, -1.7 to 0.5). Decreases in liver stiffness were significantly greater in patients treated with direct-acting antiviral agents than with interferon-based therapy (decrease of 4.5 kPa vs decrease of 2.6 kPa; P = .03), cirrhosis at baseline (decrease of 5.1 kPa vs decrease of 2.8 kPa in patients with no cirrhosis; P = .02), or high pretreatment levels of alanine aminotransferase (P < .01). Among patients with baseline liver stiffness >9.5 kPa, 47% (95% CI, 27%-68%) achieved posttreatment liver stiffness of <9.5 kPa.
CONCLUSIONS
In a systematic review and meta-analysis, we associated eradication of hepatitis C virus infection (SVR) with significant decreases in liver stiffness, particularly in patients with high baseline level of inflammation or patients who received direct-acting antiviral agents. Almost half the patients considered to have advanced fibrosis, based on VCTE, before therapy achieved posttreatment liver stiffness levels <9.5 kPa. Clinical Trial Registration no: CRD42016051034.
Topics: Antiviral Agents; Elasticity Imaging Techniques; Hepatitis C, Chronic; Humans; Liver; Sustained Virologic Response; Time Factors; Treatment Outcome
PubMed: 28479504
DOI: 10.1016/j.cgh.2017.04.038 -
Contemporary Clinical Trials Nov 2012Dosing is potentially the most important decision that must be made when building or refining behavioral interventions. In this paper, we propose standardized... (Review)
Review
Dosing is potentially the most important decision that must be made when building or refining behavioral interventions. In this paper, we propose standardized terminology and reporting of dosing information, which would inform intervention development, refinement for dissemination, and systematic reviews of dose-response relationships. Dosing of interventions may be characterized by duration, frequency, and amount. To illustrate the value of operationalizing these three parameters to evaluate dose-response relationships, 31 published reports of behavioral interventions to increase adherence to antiretroviral therapy (ART) were reviewed. The ART literature was characterized by under-reporting of dosing parameters, heterogeneity in dosing schedules, and heterogeneity in type of control group, which complicate analysis of dose-response relationships in systematic review and determination of the optimal dose for intervention dissemination. Improved reporting of the three dosing parameters and comparison of intended to actual delivery can inform the identification of the most effective intervention doses and the efficient implementation of efficacious interventions in clinical practice.
Topics: Anti-Retroviral Agents; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; HIV Infections; Humans; Randomized Controlled Trials as Topic
PubMed: 22841930
DOI: 10.1016/j.cct.2012.07.011 -
BMC Infectious Diseases Apr 2023Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and...
BACKGROUND
Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses.
METHODS
Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables.
RESULTS
In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals.
CONCLUSION
Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.
Topics: Humans; Coinfection; COVID-19 Testing; COVID-19; Virus Diseases; Cytomegalovirus Infections
PubMed: 37101275
DOI: 10.1186/s12879-023-08117-y -
BMC Gastroenterology Nov 2023Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis.
BACKGROUND
Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear.
METHODS
A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety.
RESULTS
Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period.
CONCLUSION
TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.
Topics: Humans; Tenofovir; Acute-On-Chronic Liver Failure; Antiviral Agents; Hepatitis B, Chronic; Retrospective Studies; Prospective Studies; End Stage Liver Disease; Treatment Outcome; Severity of Illness Index; Hepatitis B; Hepatitis B virus
PubMed: 37957546
DOI: 10.1186/s12876-023-03024-7 -
Alimentary Pharmacology & Therapeutics Jun 2016The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of... (Review)
Review
BACKGROUND
The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of direct-acting anti-viral (DAA) therapy provides effective treatment for patients with cirrhosis.
AIM
To systematically review the results of DAA therapy to date in patients with HCV cirrhosis, and highlight the ongoing challenges for DAA therapy in this population.
METHODS
A structured Medline search was conducted to obtain phase II and III HCV trials in patients with cirrhosis. Citations from review articles were cross-referenced and conference abstracts from EASL and AASLD liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the DAA's: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir.
RESULTS
Successful direct-acting anti-viral treatment is now possible in patients with HCV-related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response (SVR) of 90-95%. Overall success rates in GT1 cirrhosis are excellent while GT3-infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for GT3 cirrhosis achieving SVR of ~90%.
CONCLUSIONS
Potent DAA therapies provide much needed, safe and highly effective treatment options for persons with HCV cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard-to-cure groups of GT3 cirrhosis and direct-acting anti-viral failures, and managing drug-drug interactions.
Topics: Antiviral Agents; Hepatitis C; Humans; Interferons; Liver Cirrhosis
PubMed: 27087015
DOI: 10.1111/apt.13633 -
Acta Gastro-enterologica Belgica Dec 2013Mixed cryoglobulinemia (MC) is an important complication of hepatitis C virus (HCV) infection. Antiviral therapy is now an important approach for symptomatic HCV-MC;... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Mixed cryoglobulinemia (MC) is an important complication of hepatitis C virus (HCV) infection. Antiviral therapy is now an important approach for symptomatic HCV-MC; some information exists on IFN mono-therapy for symptomatic HCV-MC in the non-transplant setting, but its efficacy is still unclear.
METHODS
We evaluated efficacy and safety of mono-therapy with standard or pegylated interferon (IFN) for symptomatic HCV-associated MC in non-immunosuppressed individuals by performing a systematic review of the literature with a meta-analysis of clinical studies. We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The primary outcome was sustained viral response (SVR, as a measure of efficacy), and the secondary outcome was the drop-out rate due to side-effects (as a measure of tolerability).
RESULTS
We identified eleven clinical studies (n = 235 unique patients) ; the rate of baseline kidney involvement ranged between 11% and 74%. The summary estimate of frequency of sustained viral response was 0.15 with a 95% Confidence Interval (CI) of 0.08; 0.22 (random-effects model). Significant heterogeneity occurred (P= 0.001; Chi= 28.9%). Stratified analysis did not meaningfully change the results. The frequency of patients stopping antiviral agents was 3.4% ; most patients experienced minor side effects which did not require interruption of therapy. Baseline cirrhosis (P <0.04), kidney involvement (P <0.07), and arthralgias (P <0.04) showed negative impact on viral response. We found an excellent relationship between viral and clinical response [weighted K = 0.72 (95% CI, 0.54; 0.89)], by an evaluation at individual level on a subset of reports (n = 65 unique patients).
CONCLUSIONS
This meta-analysis of clinical studies shows that antiviral therapy with standard or pegylated IFN alone for symptomatic MC associated with HCV gives satisfactory response in a minority of patients only. Clinical trials based on combination therapy (pegylated interferon plus ribavirin) or novel immunosuppressive agents are under way in order to improve efficacy and safety of symptomatic HCV-MC. ,
Topics: Clinical Trials as Topic; Cryoglobulinemia; DNA, Viral; Hepacivirus; Hepatitis C, Chronic; Humans; Immunologic Factors; Interferon-alpha
PubMed: 24592538
DOI: No ID Found -
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 -
Liver Transplantation : Official... Jan 2013Cyclosporine A (CSA), but not tacrolimus (TAC), inhibits hepatitis C virus (HCV) replication in vitro. Clinical reports on the efficacy of interferon-α (IFNα)-based... (Meta-Analysis)
Meta-Analysis Review
Cyclosporine A (CSA), but not tacrolimus (TAC), inhibits hepatitis C virus (HCV) replication in vitro. Clinical reports on the efficacy of interferon-α (IFNα)-based antiviral therapy (AVT) for recurrent HCV after liver transplantation (LT) with CSA and TAC are conflicting. Our aim was to assess whether AVT for recurrent HCV after LT is more effective with CSA or TAC. We performed an electronic database search (1995-2012) and a manual abstract search (2005-2012). The a priori defined eligibility criteria included the use of AVT for recurrent HCV with IFN (standard or pegylated) and ribavirin and the reporting of sustained virological response (SVR) rates with CSA and TAC (the primary outcome). Two authors identified and extracted data independently. Dichotomous data were expressed as relative risks (RRs) and 95% confidence intervals (CIs) with a random effects model. In all, 5058 references were retrieved, and 1 randomized controlled trial (RCT) and 17 observational studies (13 full-text articles) met the eligibility criteria; the meta-analysis was based on the latter studies. The pooled SVR rates were 42% (395/945) with CSA and 35% (471/1364) with TAC (RR = 1.18, 95% CI = 1.00-1.39, P = 0.05). Although the pooled data contained significant heterogeneity (I(2) = 45%, P = 0.02), the SVR rates in the RCT were comparable (39% with CSA and 35% with TAC). Limiting the analysis to the 7 studies reporting on 40 or more patients in each group (with 1634 patients in all) favored CSA (RR = 1.23, 95% CI = 1.09-1.38, P < 0.001), and heterogeneity disappeared (I(2) = 0%, P = 0.62). In conclusion, IFN-based AVT for recurrent HCV after LT seems marginally more effective with CSA versus TAC; the study heterogeneity, however, limits firm conclusions.
Topics: Antiviral Agents; Cyclosporine; Female; Hepatitis C; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Tacrolimus
PubMed: 22821730
DOI: 10.1002/lt.23516