Absence Of Antiviral Therapy Research Articles

Unraveling the connection: Hepatitis C Virus (HCV) and Acute Myelogenous Leukemia (AML) in the absence of antiviral therapy

Unraveling the connection: Hepatitis C Virus (HCV) and Acute Myelogenous Leukemia (AML) in the absence of antiviral therapy

An Aptamer-Based Proteomic Analysis of Plasma from Cats (Felis catus) with Clinical Feline Infectious Peritonitis.

Feline infectious peritonitis (FIP) is a systemic disease manifestation of feline coronavirus (FCoV) and is the most important cause of infectious disease-related deaths in domestic cats. FIP has a variable clinical manifestation but is most often characterized by widespread vasculitis with visceral involvement and/or neurological disease that is typically fatal in the absence of antiviral therapy. Using an aptamer-based proteomics assay, we analyzed the plasma protein profiles of cats who were naturally infected with FIP (n = 19) in comparison to the plasma protein profiles of cats who were clinically healthy and negative for FCoV (n = 17) and cats who were positive for the enteric form of FCoV (n = 9). We identified 442 proteins that were significantly differentiable; in total, 219 increased and 223 decreased in FIP plasma versus clinically healthy cat plasma. Pathway enrichment and associated analyses showed that differentiable proteins were related to immune system processes, including the innate immune response, cytokine signaling, and antigen presentation, as well as apoptosis and vascular integrity. The relevance of these findings is discussed in the context of previous studies. While these results have the potential to inform diagnostic, therapeutic, and preventative investigations, they represent only a first step, and will require further validation.

The importance of outpatient etiotropic therapy in patients hospitalized with COVID-19

The aim of the study was to evaluate the effect of antiviral therapy prescribed at the outpatient stage on the course and outcomes of COVID-19 in hospitalized patients. Materials and methods. The retrospective study included 182 hospitalized patients with COVID-19 of moderate severity who received various initial therapy in the period before hospitalization. In the main group (91 patients), therapy included antiviral drugs: favipiravir or umifenovir, in the comparison group (also 91 patients), the treatment regimens did not contain etiotropic drugs against SARS-CoV-2. The groups were comparable in age, gender and severity of the disease. All patients received antipyretic drugs (paracetamol), vitamin therapy, according to indications – local antiseptics, mucolytics, antiplatelet agents and antibacterial drugs. The effectiveness of treatment was evaluated on days 7 and 14. Results. The presence of the virus was significantly less frequently detected on day 7 – in 15.38% and on day 14 of the disease – in 2.20% among patients receiving antiviral therapy, 82.42% and 39.56%, respectively in the comparison group. The average duration of the disease was more than 5 days less – 8.28 ± 3.74 days. The proportion of patients with a deterioration in their clinical condition to 3-4 points was significantly higher in the group that did not receive antiviral drugs – 61.54%, and with the use of favipiravir or umifenovir – 2.2%. Conclusions: 1. Timely administration of antiviral therapy for COVID-19 at the outpatient stage prevents the increase in severity, the development of complications, promotes earlier elimination of the virus and shortens the duration of the disease during hospitalization of the patient. 2. The absence of antiviral therapy with moderate severity of COVID-19 at the outpatient stage significantly increases the risk of deterioration of the patient’s condition.

Contribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression

In the absence of antiviral therapy, HIV-1 infection progresses to a wide spectrum of clinical manifestations that are the result of an entangled contribution of host, immune and viral factors. The contribution of these factors is not completely established. Several investigations have described the involvement of the immune system in the viral control. In addition, distinct HLA-B alleles, HLA-B27, -B57-58, were associated with infection control. The combination of these elements and antiviral host restriction factors results in different clinical outcomes. The role of the viral proteins in HIV-1 infection has been, however, less investigated. We will review contributions dedicated to the pathogenesis of HIV-1 infection focusing on studies identifying the function of the viral envelope glycoprotein (Env) in the clinical progression because of its essential role in the initial events of the virus life-cycle. Some analysis showed that inefficient viral Envs were dominant in non-progressor individuals. These poorly-functional viral proteins resulted in lower cellular activation, viral replication and minor viral loads. This limited viral antigenic production allows a better immune response and a lower immune exhaustion. Thus, the properties of HIV-1 Env are significant in the clinical outcome of the HIV-1 infection and AIDS pathogenesis.

Analysis of mortality and risk of death in HCV- and HCV/HIV-infected patients with extrahepatic manifestations

The aim of the study was to analyze the mortality of patients infected with the hepatitis C virus (HCV) and co-infected with the human immunodeficiency virus (HIV) with extrahepatic manifestations associated with cryoglobulinemia, and to assess the dependence of the risk of fatal outcome on such predictors as the presence of HIV infection, the presence of cirrhotic liver transformation, antiviral therapy (AVT) of chronic hepatitis C, cryoglobulin levels.Materials and Methods. The prospective study included 125 patients with HCV (n=92) and HCV/HIV infection (n=33) who had extrahepatic manifestations (arthralgia and/or skin hemorrhagic rashes and/or polyneuropathy and/or or Raynaud’s syndrome and/or xerophthalmia and/ or chronic kidney disease), as well as cryoglobulins.Results. 19 out of 125 patients (15% (95% CI 10-23%)) died in the follow-up period from 1 to 170 months (median 57 months), among which 12 people did not receive AVT for HCV infection during the follow-up period and 7 patients underwent AVT during the observation period. Unadjusted mortality among patients treated with AVT was 9% (95% CI 5–18%) (n=7/77), those who did not receive it was 25% (95% CI 15–39%) (n=12/48), χ2=5,806, p=0,016. Cox regression analysis showed that an increase in the risk of death is associated with the presence of cirrhotic liver transformation by 5,3 times and the absence of AVT by 3,7 times. The main causes of death in 69% of cases were causes not associated with liver pathology, in 26% were complications of liver cirrhosis (bleeding or progressive encephalopathy), in one case (5%) the cause of death remained unknown.Conclusions. Мortality among patients with HCV or HCV/HIV infection complicated by the development of extrahepatic manifestations associated with cryoglobulinemia is higher in the absence of AVT than in the case of AVT. Cirrhotic liver transformation and the absence of AVT significantly affect the risk of death. Patients with extrahepatic manifestations die mainly from causes not associated with liver pathology.

Estimation of the in vivo neutralization potency of eCD4Ig and conditions for AAV-mediated production for SHIV long-term remission.

The engineered protein eCD4Ig has emerged as a promising approach to achieve HIV remission in the absence of antiviral therapy. eCD4Ig neutralizes nearly all HIV-1 isolates and induces antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. To characterize the in vivo antiviral neutralization and possible ADCC effects of eCD4Ig, we fit mathematical models to eCD4Ig, anti–eCD4Ig-drug antibody (ADA), and viral load kinetics from healthy and simian-human immunodeficiency virus AD8 (SHIV-AD8) infected nonhuman primates that were treated with single or sequentially dosed eCD4Ig passive administrations. Our model predicts that eCD4Ig transiently decreases SHIV viral loads due to neutralization only with an in vivo IC50 of ~25 μg/ml but with limited effect due to ADA. Simulations suggest that endogenous, continuous expression of eCD4Ig at levels greater than 105 μg/day, as is possible with Adeno-associated virus (AAV) vector-based production, could overcome the diminishing effects of ADA and allow for long-term remission of SHIV viremia in nonhuman primates.

French multicentre observational study on SARS-CoV-2 infections intensive care initial management: the FRENCH CORONA study

AimDescribing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and indentifying risk factors of 28-day mortality. MethodsProspective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected. ResultsFrom March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58–73) years and a median SAPS II of 37 (29–48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome. ConclusionSeverity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care.

Сatamnestic data on the effect of interferon therapy on the course of combined HIV/HCV-infection

Aim: catamnestic analysis of the effectiveness of antiviral therapy for chronic hepatitis C in combination with HIV infection.Materials and methods. A retrospective study included 145 patients with combined HCV/HIV infection for 8±0,43 years.Results. 55% of patients received antiviral therapy for chronic hepatitis with pegylated interferons and ribavirin. The frequency of achieving a stable virological response is 73%. Persistent virological response with favorable Il-28B genotypes was detected in 85% of cases, with unfavorable genotypes less frequently — in 63% (p=0,028); the relapse rate is 27%. The level of HIV RNA viral load and the frequency of patients with secondary diseases was higher in patients with natural HCV/HIV infection with favorable interleukin-28B genotypes compared to other comparison groups (р<0,05).Conclusion. The course of chronic hepatitis C after therapy was more positive with favorable Il-28B genotypes. HIV infection was more severe in the absence of antiviral therapy for chronic hepatitis C.

Guidelines and Safety Considerations in the Laboratory Diagnosis of SARS-CoV-2 Infection: A Prerequisite Study for Health Professionals.

Coronavirus disease 2019 (COVID-19) is an emerging challenging area for the researchers to buckle up against the spread and control of the virus. Since earlier times, the diagnosis has been an important procedure in estimating the fate of epidemics by indicating the extent to which disease has been spread and to the extent, further disease prognosis would occur. The absence of anti-viral therapies and vaccines for COVID-19 at present suggests early diagnosis and isolation of the patients as the only smart approach available as of now. Presently, the increasing death rates, faster rates of transmission, non-availability of vaccines, and treatment have over-pressurized the researchers, health professionals, and government officials to develop effective clinical strategies in diagnosis and to come up with guidelines to be followed during conduction of each diagnostic procedure for maintaining healthcare systems. Since the incubation period of this virus is 2–14 days, a patient can transmit the infection without showing symptoms. Therefore, early diagnosis and isolation of susceptible individuals are the only way to limit the spread of the virus. Significance of diagnosis and triaging, information on specimen collection, safety considerations while handling, transport, and storage of samples have been highlighted in this paper to make people more aware and develop better clinical strategies in the future.

Innate Immune Subversion Strategies of Human Flaviviruses.

Flavivirus is a genus of medically important viruses, including Dengue virus (DENV), Zika virus (ZIKV), Yellow Fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV), etc. The global burden of these acute infection-causing viruses is ever-increasing. Primary febrile symptoms of most of these viruses can progress to hemorrhagic or neurological complications, and some like JEV, YFV have a greater than 15% mortality. The absence of antiviral therapy and highly effective vaccine candidates for these viruses highlights the need for research into virulence and immune evasion mechanisms at the molecular level. Interaction with the host needs to be carefully dissected to narrow down to a list of necessary factors for virus survival within the host. This review attempts to comprehensively compile research efforts made in the field of innate immune subversion strategies employed by the human Flaviviruses.

1411. Risks and Outcomes of Adenovirus Disease in Pediatric HSCT Recipients –Comparison of Current Antiviral Treatment Options

BackgroundAdenovirus can cause multi-organ dysfunction in hematopoietic stem cell transplant recipients (SCTr). It accounts for 22% of infection-associated mortality in umbilical cord transplant recipients (UCTr). This study determines whether transplant characteristics are associated with risk of adenovirus disease (ADVd), and compares time to resolution of ADVd between patients who received antiviral therapy.MethodsWe conducted a retrospective single center cohort study of pediatric patients undergoing stem cell transplant at Duke University between 2005 and 2016. We identified cases of single end-organ and disseminated ADVd (2 or more organs) using a classification tool defined a priori. We used a Cox proportional hazards (CPH) regression model to compare the hazard of ADVd between SCTr differing by type of transplant and type of conditioning regimen. We also used CPH to compare the hazard of time to resolution of ADVd between SCTr differing by absence or presence of antiviral therapy (cidofovir, brincidofovir or both).ResultsThere are 830 subjects, including 93 subjects with ADVd post-SCT. UCTr had 3.30 times the hazard of developing ADVd compared to non-cord blood allogeneic transplants and 7.30 times the hazard compared to autologous transplants (Figure 1). No difference in hazard of ADVd was detected between patients who received myeloablative vs non-myeloablative conditioning. Twenty-seven percent of the subjects received antiviral therapy; these patients had higher mortality (38%). The majority (87%) of diseased subjects had resolution of disease. Subjects that did not receive antiviral therapy experienced earlier resolution of ADVd compared to subjects who received antiviral therapy even after adjusting for subjects with disseminated disease (HR (95% CI): 3.75 (1.57, 8.93), p=0.003). Subjects with single end organ disease had earlier resolution of ADVd compared to disseminated disease (HR (95% CI): 2.24 (1.22, 4.10), p=0.009).Figure 1a. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of transplant. Figure 1b. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of conditioning regimen. ConclusionThis is the first pediatric cohort study to report risk factors and clinical outcomes of ADVd, irrespective of ADV-DNAemia. UCTr recipients have a higher hazard of ADVd compared to other SCTr. Contrary to previous reports studying ADV-DNAemia, our study noted an earlier resolution of ADVd in the absence of antiviral therapy.Disclosures All Authors: No reported disclosures

Nivolumab in patients with metastatic renal cell carcinoma and chronic hepatitis C virus infection.

Hepatitis C virus (HCV) interferes with activation of innate and adaptive immune responses. Theoretically, the efficacy and toxicity of immune checkpoint inhibitors in cancer patients infected with HCV may differ. Nevertheless, HCV was an exclusion criterion in most checkpoint inhibitor trials. We evaluated the efficacy and safety of nivolumab in metastatic renal cell carcinoma (mRCC) patients with or without chronic HCV infection. In a matched cohort study, data were collected from 174 patients, retrospectively. All patients had clear-cell mRCC, chronic HCV infection (case study group), no evidence of other malignancy or cirrhosis, and had received nivolumab (3mg/kg every 2weeks) until disease progression or unacceptable toxicity. Quantitation of HCV RNA in plasma samples was performed before and during treatment with nivolumab with the automated HCV test (Hoffmann-La Roche, Switzerland). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and rate of grade 3-4 adverse events in study and control cohorts. A total of 44 matched patients were included. Groups were well balanced. HCV-infected patients had significantly longer OS and PFS. Median OS was 27.5 (95% CI 25.3-29.7) and 21.7 (20.3-23.1) in study and control groups, respectively (P = 0.005). Median PFS was 7.5 (5.7-9.3) and 4.9 (4-5.8) (P = 0.013). Despite no differences in ORR between groups (27% vs. 23%, P = 0.7), patients with HCV had significantly more durable responses (P = 0.01). Nivolumab was well tolerated in all HCV-positive patients. No unexpected toxicity was observed. Assessment of viral load during nivolumab therapy was available in 14 of 22 (64%) patients with HCV. Nivolumab did not significantly impact HCV concentration (mean change 210IU/ml, P = 0.82) in the absence of antiviral therapy. The efficacy and safety profiles observed in this study support the administration of nivolumab in mRCC patients infected with HCV and warrant further investigation.

NEW PROGNOSTIC METHOD FOR ESTIMATION OF LIPID DISTRESS SYNDROME DEVELOPMENT IN PATIENTS WITH CHRONIC HEPATITIS C

Objectives - to work out a prognostic method, based on clinical and laboratory data, which can predict the development of lipid distress syndrome in patients with chronic viral hepatitis C. Material and methods. We studied the outcomes of chronic viral hepatitis C with respect to development of lipid distress syndrome in 267 patients who did not receive antiviral therapy during the observation period lasting for 1 to 7 years. Results. Discriminant function analysis of the data acquired after examination of 167 patients helped us to work out a discriminative model of predicting the development of lipid distress syndrome in patients with chronic viral hepatitis C in the absence of antiviral therapy. Crosschecking of prediction accuracy was carried out on the data of examination of other 100 patients. Conclusion. The designed technique for predicting the development of lipid distress syndrome in patients with chronic hepatitis C is characterized by point estimates of sensitivity and prognostic value of the negative result equal to 100%.

Risk factors of unfavorable prognosis of chronic hepatitis C.

To investigate risk factors of unfavorable prognosis in patients with chronic hepatitis C (CHC), including liver cirrhosis (LC), decompensated cirrhosis, hepatocellular carcinoma (HCC), cryoglobulinemic vasculitis (CryoVas) and B-cell non-Hodgkin's lymphoma. This was a retrospective study using data of 824 patients with CHC hospitalized between 2010 and 2016 in clinic named after E.M. Tareev. We used multivariate analysis including logistic regression to calculate odds ratios (ORs) for potential risk factors/predictors associated with unfavorable outcomes in patients with CHC. The rate of LC, decompensated LC, HCC, serious CryoVas and B-cell lymphoma in patients with CHC was 39.1% (322/824), 14.0% (115/824), 2.8% (23/824), 5.2% (43/824) and 1.2% (10/824), respectively. After adjustment for sex and age the rate of LC, decompensated LC, HCC was 22.8, 8.0 and 1.5%, respectively. Annual rate of LC in patients with CHC was 1.5%; in cirrhotic patients annual rate of decompensated LC and HCC was 2.9 and 1%, respectively. Risk factors independently associated with development of LC were elevated body mass index (OR 1.43), immunosuppressive therapy (OR 1.67), diabetes type 2 (OR 2.03), absence of antiviral therapy (OR 2.15), alcohol abuse (OR 2.34), duration of infection ≥20 years (ОR 2.74) and an absence of sustained virological responce (SVR) (OR 2.98). Independent risk factors for decompensation in cirrhotic patients included diabetes type 2 (OR 1.47), alcohol abuse (OR 1.53), an absence of antiviral therapy (OR 2.36) and an absence of SVR (OR 1.94). An episode of decompensation was the independent predictor of HCC in cirrhotic patients (OR 3.99). Genotype 1b (OR 1.66) and an absence of antiviral therapy (OR 3.31) were independently associated with serious CryoVas. Two prognostic scales were offered for risk evaluation of LC and its complications. Multivariate analysis showed several factors independently associated with higher risk for LC, decompensation of LC, HCC, serious CryoVas in patients with CHC. The rate of unfavorable outcomes of CHC is found, including rare extrahepatic manifestations.

Возможности прогнозирования развития метаболического синдрома у пациентов хроническим вирусным гепатитом С при отсутствии противовирусной терапии

Возможности прогнозирования развития метаболического синдрома у пациентов хроническим вирусным гепатитом С при отсутствии противовирусной терапии

Modelling the emergence of influenza drug resistance: The roles of surface proteins, the immune response and antiviral mechanisms.

The emergence of influenza drug resistance has become of particular interest as current planning for an influenza pandemic involves using massive amounts of antiviral drugs. We use semi-stochastic simulations to examine the emergence of drug resistant mutants during the course of a single infection within a patient in the presence and absence of antiviral therapy. We specifically examine three factors and their effect on the emergence of drug-resistant mutants: antiviral mechanism, the immune response, and surface proteins. We find that adamantanes, because they act at the start of the replication cycle to prevent infection, are less likely to produce drug-resistant mutants than NAIs, which act at the end of the replication cycle. A mismatch between surface proteins and internal RNA results in drug-resistant mutants being less likely to emerge, and emerging later in the infection because the mismatch gives antivirals a second chance to prevent propagation of the mutation. The immune response subdues slow growing infections, further reducing the probability that a drug resistant mutant will emerge and yield a drug-resistant infection. These findings improve our understanding of the factors that contribute to the emergence of drug resistance during the course of a single influenza infection.

Effects of antiviral therapy on post-hepatectomy HBV reactivation and liver function in HBV DNA-negative patients with HBV-related hepatocellular carcinoma.

The ability of antiviral therapy to reduce risk of post-hepatectomy hepatitis B virus (HBV) reactivation in patients negative for viral DNA is unclear. This prospective study involved 174 consecutive patients with hepatitis B virus related hepatocellular carcinoma who were negative for hepatitis B virus DNA in serum and who underwent hepatic resection. Hepatitis B virus reactivation occurred in 30 patients in the non-antiviral group (27.8%) but in only 2 patients in the antiviral group (3.0%, P < 0.001). Based on multivariate analysis, risk of hepatitis B virus reactivation was associated with minor hepatectomy and absence of antiviral therapy. Liver function indicators at one week after resection did not differ significantly between the two groups, or between patients who experienced hepatitis B virus reactivation or not. Nevertheless, alanine aminotransferase and albumin at 1 month after resection were significantly higher in the antiviral group than in the non-antiviral group, and they were significantly higher in patients who did not experience hepatitis B virus reactivation than in those who did. Therefore, patients with hepatitis B virus related hepatocellular carcinoma face substantial risk of hepatitis B virus reactivation after hepatectomy, even if they are negative for viral DNA at baseline. Antiviral therapy can reduce the risk of reactivation, helping improve liver function after surgery. (Clinicaltrials.gov registration number: NCT02829359).

Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization.

Background/AimsHepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE.MethodsThis retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC.ResultsOf the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation.ConclusionOur findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.

Hepatitis B reactivation in patients with solid tumors: A systematic review and meta-analysis.

138 Background: Hepatitis B virus (HBV) affects over 250 million people worldwide. Most people with chronic HBV (HBsAg positive) have no signs or symptoms of infection. However, when exposed to immunosuppression they are at risk of HBV reactivation which can cause hepatitis, liver failure and death. The risk of HBV reactivation in patients receiving chemotherapy for solid tumors, the efficacy of antiviral prophylaxis, and the clinical impact of HBV reactivation in this setting are uncertain. Primary Aim: To estimate the risk of clinical HBV reactivation (increased HBV DNA + transaminitis) among HBsAg-positive patients administered chemotherapy for a solid tumor. Secondary Aims: To estimate the efficacy of anti-viral prophylaxis and the risk of death from HBV reactivation in patients receiving chemotherapy for solid tumors. Methods: A systematic review and meta-analysis of the English language literature on HBV reactivation was completed (OVID Medline, 1946 to Aug 2013). All citations were reviewed by two or more authors. Data from patients with hematologic malignancies were excluded. Pooled probabilities of HBV reactivation risk, death from HBV reactivation, and odds ratio for the impact of anti-viral prophylaxis were estimated with a random effects model. Results: 2,667 citations were identified; 19 were eligible for inclusion. The pooled estimate for clinical HBV reactivation in HBsAg-positive patients receiving chemotherapy for a solid tumor was 21.9% (95% CI; 16.5% to 27.3%) in those not receiving anti-viral prophylaxis, and 2.4% (95% CI 0.7% to 4.2%) in those receiving anti-viral prophylaxis. The odds ratio for clinical HBV reactivation with antiviral prophylaxis compared to no prophylaxis was 0.12 (95% CI 0.06 to 0.25). In the absence of viral prophylaxis, the risk of dying from HBV reactivation in HBsAg-positive solid tumor patients was estimated at 1.3% with a 95% CI of 0.3% to 2.3%. Conclusions: Patients with chronic HBV who are administered chemotherapy for a solid tumor appear to be at substantial risk of clinical HBV reactivation; this risk may be mitigated by anti-viral prophylaxis. In the absence of anti-viral therapy, patients may experience a small but important risk of dying from HBV reactivation.

Integrase inhibitor reversal dynamics indicate unintegrated HIV-1 dna initiate de novo integration.

BackgroundGenomic integration, an obligate step in the HIV-1 replication cycle, is blocked by the integrase inhibitor raltegravir. A consequence is an excess of unintegrated viral DNA genomes, which undergo intramolecular ligation and accumulate as 2-LTR circles. These circularized genomes are also reliably observed in vivo in the absence of antiviral therapy and they persist in non-dividing cells. However, they have long been considered as dead-end products that are not precursors to integration and further viral propagation.ResultsHere, we show that raltegravir action is reversible and that unintegrated viral DNA is integrated in the host cell genome after raltegravir removal leading to HIV-1 replication. Using quantitative PCR approach, we analyzed the consequences of reversing prolonged raltegravir-induced integration blocks. We observed, after RAL removal, a decrease of 2-LTR circles and a transient increase of linear DNA that is subsequently integrated in the host cell genome and fuel new cycles of viral replication.ConclusionsOur data highly suggest that 2-LTR circles can be used as a reserve supply of genomes for proviral integration highlighting their potential role in the overall HIV-1 replication cycle.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0153-9) contains supplementary material, which is available to authorized users.