Antiviral Therapy

BACKGROUND: This real-world clinical-setting study characterized the virological patterns in genotype-1 patients failing IFN-free regimens and evaluated the efficacy of re-treatment. METHODS: Seventy-three consecutive patients failing IFN-free regimens were enrolled (17 genotype 1a and 56 1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols. RESULTS: In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype 1a than in the 24 with genotype 1b (80% vs...

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen and causes significant economic losses to the swine industry worldwide each year. Current vaccination strategies do not effectively prevent and control the virus. Consequently, it is necessary to develop novel antiviral strategies. Carrageenan, extracted from marine red algae, exhibits anti-coagulant, anti-tumor, anti-virus and immunomodulatory activities. METHODS: We investigate the inhibitory effect of iota-carrageenan (CG) on PRRSV strain CH-1a via antiviral assay and viral binding, entry and release assays...

BACKGROUND: We compared time to treatment change (TC), viral suppression (VS) and change in CD4+ T-cell counts of first-line antiretroviral regimens (ART). METHODS: We analyzed HIV treatment-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) initiating the most commonly used ART regimens from September 2014 to November 2015. We used proportional hazards models on the sub-distribution hazard to estimate sub-distribution hazard ratios (sHR) for time to TC, logistic regression to estimate odds ratios (ORs) for VS (viral load<50 copies/ml), and linear regression to assess mean differences in CD4 changes from ART initiation...

INTRODUCTION: Sentinel surveillance of transmitted HIV drug resistance (TDR) among recently infected populations within a country was recommended by the World Health Organization from 2004-2015. METHODS: Serum specimens collected as part of the 2010, 2011 and 2012 National Antenatal Sentinel HIV Prevalence Surveys were used to estimate provincial and national TDR prevalence in South Africa. RESULTS: Moderate (5-15%) levels of transmitted non-nucleoside reverse transcriptase inhibitors (NNRTI) drug class resistance were detected in 3 of 5 provinces surveyed in 2010 and 2011 (Eastern Cape, Free State and KwaZulu-Natal)...

BACKGROUND: Physiological changes during pregnancy can have a significant impact on antiretroviral pharmacokinetics (PK), which may result in reduced drug efficacy. Here we describe the PK of darunavir/ritonavir (DRV/r) 800/100 QD in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM) as well as transplacental passage of DRV by measuring and comparing cord blood and maternal blood samples at delivery. METHODS: Pregnant HIV-positive women received DRV/r as part of routine pre-natal care...

BACKGROUND: Polypharmacy (use of ≥ 5 medications) increases the risk of drug-drug interactions and can lead to negative health outcomes. This study aimed to review the medications of people living with HIV (PLWH) and HIV negative controls in the POPPY study and evaluate the frequency of polypharmacy and potential drug-drug interactions (PDDI). METHODS: Potential drug-drug interactions between non-antiretroviral (ARV) drugs were analysed using the Lexicomp® database, and PDDI between non-ARV and ARV drugs using the Liverpool drug interaction database...

BACKGROUND: Our objectives were to review the economic modelling methods and cost-effectiveness of second generation direct-acting antiviral agents for the treatment of chronic hepatitis C virus infection. METHODS: A systematic literature search was performed in February 2017 using Scopus and OVID to review relevant publications between 2011 to present. Two independent reviewers screened potential papers. RESULTS: The database search resulted in a total of 1,536 articles; after deduplication, title/abstract and full text screening 67 studies were included for qualitative analysis...

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BACKGROUND: There are controversial data on possible occult hepatitis B virus (HBV) reactivation in hepatitis C virus (HCV) patients successfully treated with direct-acting antivirals (DAA). However, diagnosis of occult HBV infection (OBI) was not performed by gold standard procedures in any study. METHODS: By using several highly sensitive assays, we examined serially collected serum samples from 40 HBV-surface-negative DAA-treated HCV patients with OBI identified by testing liver biopsy specimens through nested-PCR technique...

BACKGROUND: We have used a comprehensive HIV population to characterize antiretroviral therapy (ART), drug class selection, pill burden, drug costs and health outcomes over the entire span of the HIV epidemic. METHODS: Antiretroviral (ARV) use (drugs, classes, formulations) and both the laboratory and clinical outcomes (HIV1-RNA, CD4 cell count, and mortality) were determined for all patients in Southern Alberta, Canada, at each year-end between 1986 and 2017. Pill burden, cumulative drug exposure and costs were calculated for each year...

BACKGROUND: Frailty and falls occur commonly and prematurely in HIV-infected populations. Whether frailty in middle-age predicts future falls among HIV-infected women is unknown. METHODS: We evaluated associations of frailty with single and recurrent falls 10 years later among 729 HIV-infected and 326 uninfected women in the Women's Interagency HIV Study (WIHS) with frailty measured in 2005 and self-reported falls in 2014-2016. Frailty was defined as ≥3 of 5 Fried Frailty Index components: slow gait, reduced grip strength, exhaustion, unintentional weight loss, and low physical activity...

BACKGROUND: Cancer is a leading cause of death in HIV-infected patients in the era of combination antiretroviral therapy (cART). Yet, there are no specific guidelines for the combined use of cART and chemotherapy in HIV-infected cancer patients. The cellular enzyme thymidylate synthase (TS) catalyzes the conversion of dUMP to TMP, which is converted to TDP and ultimately to TTP, a building block in DNA synthesis. TS inhibitors are recommended in some cancers, particularly non-small cell lung cancer (NSCLC)...

BACKGROUND: Tenofovir disoproxil fumarate (TDF) administration in the third trimester for pregnant women with high HBV DNA load has been accepted as a wise practice to prevent mother-to-infant transmission (MTIT). However, for those women who missed the optimal time window of antiviral prophylaxis, the emergent treatment is lacked in the current clinical guidelines. METHODS: Forty-eight pregnant women who did not receive antiviral prophylaxis before 28 weeks of gestation were screened and were administrated with TDF plus hepatitis B immunoglobulin (HBIG, TDF+HBIG group) or TDF alone (TDF group)...

BACKGROUND: Limited data exist on efavirenz pharmacokinetics in HIV-positive pregnant women and neonatal washout. METHODS: HIV-infected pregnant women receiving 600 mg efavirenz once daily had intensive steady-state 24-hour pharmacokinetics profiles during the second trimester (2T), third trimester (3T) and 6-12 weeks postpartum (PP). Maternal and umbilical cord blood samples were drawn at delivery and neonatal washout pharmacokinetics were determined. Therapeutic targets were the estimated 10th percentile efavirenz area under the concentration-time curve (AUC) in non-pregnant historical controls (40...

BACKGROUND: Recent studies suggest that serum lipids are associated with pegylated interferon-alpha (PegIFNα) treatment response in chronic hepatitis C patients. However, the role of serum lipids in influencing the outcome of HBV treatment is not well understood. This study aims to investigate the association of serum lipids with the response to interferon-alpha treatment for chronic hepatitis B (CHB) patients. METHODS: We dynamically measured 11 clinical serum lipid parameters of 119 HBeAg-positive CHB patients, including 53 patients who achieved sustained response (SR) and 66 patients who achieved nonresponse (NR) induced by PegIFNα treatment for 48 weeks...

BACKGROUND: Hepatitis D virus (HDV) infection is a cause of severe liver disease. Diagnosis and monitoring of HDV RNA are important to patient management. Since 2012 a WHO standard for HDV RNA quantification is available, however, the impact of RNA extraction methods on HDV viral load quantification has never been evaluated. METHODS: Aim of this study was to compare four commonly used automated nucleic acid (NA) extraction methods (AmpliPrep, MagNA Pure, QIAcube QBK and QIAcube VRK) to a manual RNA extraction method (Instant Virus RNA/DNA kit) and evaluate the possible effect of each method on HDV RNA yield with subsequent amplification with the Robogene HDV assay...

BACKGROUND: This study was aimed at evaluating the clinical significance of serum hepatitis B virus (HBV) RNA, HBcrAg, and anti-HBc levels in chronic hepatitis B patients with undetectable HBV DNA during nucleoside/nucleotide analog (NA) treatment. METHODS: Fifty-seven patients who received long-term NA treatment of median 5.83 (4.67, 7.75) years were enrolled, and 285 serum samples at five time points for each patient were quantitatively analyzed for the three serum markers together with serum HBV DNA and HBsAg levels...

BACKGROUND: Infections due to drug-resistant herpes simplex viruses (HSV) represent an important clinical concern, especially in the immunocompromised patients. The present study was aimed at detecting acyclovir (ACV) susceptibility in HSV clinical samples. METHODS: A total of 13 HSV-positive clinical samples (five HSV-1 and eight HSV-2) recovered from patients (one immunocompromised, and 12 of unknown immune status) were included in the study. The genotypic analysis involved an initial UL23 (thymidine kinase) gene sequencing, followed by a confirmatory phenotypic assay using plaque reduction technique...

BACKGROUND: Optimal treatment for patients with hepatitis C virus (HCV) genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks. METHODS: This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12); the primary objective was to demonstrate statistical superiority to historical SVR12 data for 12 weeks' daclatasvir+sofosbuvir without ribavirin in genotype-3-infected patients with cirrhosis (95% confidence interval [CI] lower bound >79...

BACKGROUND: The male genital tract (MGT) is a viral sanctuary and likely HIV reservoir; understanding MGT pharmacokinetics (PK) of antiretrovirals (ARVs) used for curative strategies is critical to eradication and cure. Tenofovir alafenamide (TAF) is a tenofovir (TFV) formulation designed to maximize efficacy/minimize toxicity with unknown MGT PK. METHODS: HIV-positive and HIV-negative men receiving TFV-based regimens provided 6 paired blood plasma (BP) and semen samples...