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Antiviral Efficacy (antiviral + efficacy)

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Medical Sciences	100%

Selected Abstracts

Antiviral efficacy and resistance in patients on antiretroviral therapy in Kigali, Rwanda: the real-life situation in 2002

HIV MEDICINE, Issue 1 2006
A Fischer
Our study aimed to complete the published data on ARV therapy in Africa by describing the baseline situation in Rwanda before the launch of a large ARV programme (ESTHER). Prescription habits, frequency and reasons for treatment interruptions but also antiviral efficay, resistance to ARVs and genotypic variability of the viruses present in Rwanda were analysed. Among the 233 patients included in the study, it appeared that a vast majority (91%) were under triple therapy and that half of them had experienced at least one treatment interruption caused mainly by drug shortage or financial difficulties. Among 60 blood samples analysed, 26 were in virological failure with a viral load above 1000 RNA copies/ml and 11 presented major drug resistance mutations. Finally, virological failure could mainly be explained by the high frequency of treatment interruptions but also by the emergence of drug resistance mutations. Consequently the major objective for the ESTHER programme to improve the situation in Rwanda will be to reduce the drug shortage and facilitate the financial accessibility of the treatments. [source]

Lack of response to exogenous interferon-, in the liver of chimpanzees chronically infected with hepatitis C virus,,

HEPATOLOGY, Issue 4 2007
Robert E. Lanford
The mechanism of the interferon-alpha (IFN,),induced antiviral response is not completely understood. We recently examined the transcriptional response to IFN, in uninfected chimpanzees. The transcriptional response to IFN, in the liver and peripheral blood mononuclear cells (PBMCs) was rapidly induced but was also rapidly down-regulated, with most interferon-alpha,stimulated genes (ISGs) returning to the baseline within 24 hours. We have extended these observations to include chimpanzees chronically infected with hepatitis C virus (HCV). Remarkably, using total genome microarray analysis, we observed almost no induction of ISG transcripts in the livers of chronically infected animals following IFN, dosing, whereas the response in PBMCs was similar to that in uninfected animals. In agreement with this finding, no decrease in the viral load occurred with up to 12 weeks of pegylated IFN, therapy. The block in the response to exogenous IFN, appeared to be HCV-specific because the response in a hepatitis B virus,infected animal was similar to that of uninfected animals. The lack of a response to exogenous IFN, may be due to an already maximally induced ISG response because chronically HCV-infected chimpanzees already have a highly up-regulated hepatic ISG response. Alternatively, negative regulation may block the response to exogenous IFN,, yet it does not prevent the continued response to endogenous ISG stimuli. The IFN, response in chronically HCV-infected chimpanzees may be mechanistically similar to the null response in the human population. Conclusion: In chimpanzees infected with HCV, the highly elevated hepatic ISG expression may prevent the further induction of ISGs and antiviral efficacy following an IFN, treatment. (HEPATOLOGY 2007.) [source]

Effect of food on the antiviral activity of didanosine enteric-coated capsules: a pilot comparative study,

HIV MEDICINE, Issue 4 2008
B Hernández-Novoa
Objectives To determine the effect of food on the antiviral activity of enteric-coated (EC) capsules of didanosine (ddI). Methods We conducted a pilot, randomized, open-label study of 28-day ddI-EC capsules monotherapy-administered in a fasted state (group 1, n=11) or with food (group 2, n=10) to treatment-naïve chronically HIV-1-infected individuals. To assess the antiviral efficacy, HIV-1 RNA was determined at baseline, day 3, day 7 and weekly thereafter. The area under the HIV-1 RNA curve minus baseline weighted by time (AUCMB/day) was calculated. Results Mean baseline HIV-1 RNA was 4.2 log10 copies/mL in group 1 and 3.8 log10 copies/mL in group 2. After 28 days, the mean HIV-1 RNA reduction was 0.99 log10 copies/mL [95% confidence interval (CI) 0.45,1.53] for group 1 and 0.89 log10 copies/mL (95% CI 0.38,1.40) for group 2. AUCMB/day values were 0.775 log10 copies/mL (95% CI 0.33,1.22) and 0.774 log10 copies/mL (95% CI 0.48,1.07), respectively, showing no difference in the rate of decrease of HIV-1 RNA (P=0.995). Mean ddI plasma levels at day 28 were 0.0234 mg/L for group 1 and 0.0227 mg/L for group 2 (P=0.96). Conclusions In this pilot study, the administration of food did not have any significant effect on the antiviral activity of ddI-EC capsules. [source]

TRIZAL study: switching from successful HAART to TrizivirTM (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence results

HIV MEDICINE, Issue 2 2003
C Katlama
Objective To assess the antiviral efficacy, safety, and adherence in subjects who switched to TrizivirÔ following long-term HIV-1 RNA suppression. Study design A randomized, open-label, multicentre, 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months, with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening. Methods Subjects were randomized 1:1 to continue their current treatment or to switch to a simplified treatment with TrizivirÔ administered twice daily. Assessments included plasma HIV-1 RNA, lymphocyte counts, clinical laboratory evaluations, adverse events, and adherence to treatment (obtained via subject self-report). Treatment failure was defined as a plasma viral load of , 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of randomized treatment. Results At week 48, the proportion of treatment failures in TrizivirÔ arm (23/106, 22%) was noninferior to that observed in continued arm (23/103, 22%) with a treatment difference stratified by prior ART of 1.2%[-10.1; 12.5]. Incidence of adverse events was similar in both treatment groups. The incidence of possible hypersensitivity reaction in the TrizivirÔ arm was 10%. Significant reductions in cholesterol and triglyceride plasma levels were observed in the TrizivirÔ arm (P < 0.001 and P = 0.006, respectively). Conclusion Switching to TrizivirÔ offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy. [source]

In vitro effect of oral antiseptics on human immunodeficiency virus-1 and herpes simplex virus type 1

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2001
A. A. M. A. Baqui
Abstract Aim: The antiviral effectiveness of widely used commercial mouthrinses has not been well studied. A project was undertaken to evaluate and compare the in vitro antiviral effectiveness of essential oil-containing mouthrinses (LA & TLA) and chlorhexidine mouthrinses (PX & CHX) on 2 different enveloped viruses, human immunodeficiency virus (HIV-1) and Herpes simplex virus (HSV-1) McIntyre strain. Method: HIV-189.6 (1×105/ml) and HSV-1 (1×106/ml) in RPMI-1640 medium were treated with two commercially available forms of LA & TLA (tartar control LA), and 2 formulations of chlorhexidine [(PX), 0.12% chlorhexidine & (CHX), 0.2% chlorhexidine] for 30 sec. The antiviral effect was estimated by inhibition of the syncytia formation or the cytopathic effect (CPE) for HIV-1 on MT-2 cells and by inhibition of the plaque formation for HSV-1 on Vero cell monolayers. Results: Undiluted LA, TLA, PX and CHX completely inhibited both HIV-189.6 and HSV-1 McIntyre strain. PX and CHX inhibited HIV-1 up to 1:4 dilution, whereas, LA and TLA inhibited HSV-1 up to 1:2 dilution. The antiviral effects of LA and TLA were found to be similar and also the antiviral effect of PX and CHX were also found to be comparable. Conclusions: The methods used in this investigation allow easy and reproducible evaluations of antiviral efficacy. The anti-HIV-1 and anti-HSV-1 effects of LA, TLA, PX and CHX as evidenced in our in vitro study suggest that we should investigate potential in vivo effects during the use of essential oil-containing or chlorhexidine containing products when used by patients as mouthrinses. If the clinical studies confirm the in vitro data, pre-procedural use by clinicians may be beneficial in reducing viral contamination of bio-aerosols during the delivery of dental care. Zusammenfassung Ziel: Die antivirale Effektivität von breit genutzten kommerziellen Mundwässern wurde bisher nicht gut untersucht. Ein Projekt wurde deshalb aufgenommen, um den in vitro antiviralen Effekt von ätherischen Öl enthaltenden Mundwässern (LA & TLA) und Chlorhexidin Mundwässern (PX & CHX) auf 2 unterschiedlich entwickelte Viren, das menschliche Immundefizienz Virus (HIV-1) und das Herpes simplex Virus (HSV-1) McIntyre Stamm zu evaluieren und zu vergleichen. Methoden: HIV-189.6 (1×105/ml) und HSV-1 (1×106/ml) in RPMI-1640 Medium wurden mit 2 kommerziellen Formen von LA & TLA (Tartarkontrolle LA) und 2 Arten von Chlorhexidin [(PX), 0.12% Chlorhexidin & (CHX), 0.2% Chlorhexidin] für 30 Sekunden behandelt. Der antivirale Effekt wurde durch Inhibition der Syncytiumbildung oder des cytopathischen Effektes (CPE) für HIV-1 auf MT-2 Zellen und durch Inhibition der Plaquebildung für HSV-1 auf Vero Zellmonolayers bestimmt. Ergebnisse: Unverdünntes LA, TLA, PX und CHX inhibierte sowohl HIV-189.6 und HSV-1 McIntyre Stamm. PX und CHX inhibierte HIV-1 bis zu einer 1:4 Verdünnung, während LA und TLA HSV-1 bis zu einer 1:2 Verdünnung inhibierte. Die antiviralen Effekte von LA und TLA wurden gleichwertig gefunden und auch der antivirale Effekt von PX und CHX waren vergleichbar. Zusammenfassung: Die genutzten Methoden in dieser Untersuchung erlaubten leicht und reproduzierbar die Evaluation von antiviralen Effekten. Die anti-HIV-1 und anti-HSV-1 Effekte von LA, TLA, PX und CHX, die in unserer in vitro Studie evident waren, suggerieren, daß wir das Potential der in vivo Effekte während des Gebrauches von ätherischen Öl enthaltenden oder Chlorhexidin enthaltenden Produkten untersuchen sollten, wenn die Patienten dies als Mundwässer benutzen. Wenn die klinischen Studien die in vitro Ergebnisse bestätigen, kann der vorherige Gebrauch durch die Kliniker die virale Kontamination von Bioaerosolen während der durchgeführten zahnäztlichen Behandlung reduzieren. Résumé But: L'efficacité antivirale des bains de bouches largement commercialises n'a pas été bien étudiée. Notre projet a évalué et comparé l'efficité antivirale in vitro de bains de bouche aux huiles essentielles (LA et TLA) et à la chlorexhidine (PX et CHX) sur 2 virus à envelopes, le virus de l'immunodéfiscience acquise 1 (HIV1) et la souche McIntyre du virus de l'Herpes simplex de type 1 (HSV1). Méthode: HIV1896 (1×105/ml) et HSV1 (1×106 ml) dans un milieu RPMI-1640 furent traits avec 2 formes disponibles sur le marché de LA et TLA, et 2 formules de chloxhexidine (PX, 0.12% chlorexhidine et CHX, 0.2% chlorexhidine) pendant 30 s. L'effet antiviral fut estimé par l'inhibition de la formation de syncitia ou par l'effet cytopathique (CPE) pour HIV1, sur des cellules MT2 et par l'inhibition de la formation de plaque pour HSV1 sur des monocouches cellulaires Vero. Résultats: CHX, LA, TLA et PX non dilués inhibaient complètement à la fois HIV1896 et la souche McIntyre HSV1. PX et CHX inhibaient HIV1 jusqu'à une dilution par 4 alors que LA et TLA inhibaient HSV1 jusqu'à une dilution par 2. Les effets antiviraux de LA et TLA étaient similaires, et les effets antiviraux de PX et CHX étaient aussi comparables. Conclusions: Les methodes utilisées pour cette recherche permettent une évaluation facile et reproductible de l'efficacité antivirale. Les effets anti-HIV1 et anti-HSV1 de LA, TLA, PX et CHX trouvés ici in vitro suggèrent que nous recherchions des effects potentiels in vivo lors de l'utilisation de produits contenant des huiles essentielles ou de la chlorexhidine utilisés comme bains de bouches par les patients. Si les études cliniques confirment les données in vitro, l'utilisation préclinique par les praticiens pourrait leur être bénéfique en réduisant la contamination virale des bioaérosols lors des soins dentaires. [source]

Worse recent efficacy of antiviral therapy in liver transplant recipients with recurrent hepatitis C: Impact of donor age and baseline cirrhosis,

LIVER TRANSPLANTATION, Issue 7 2009
Marina Berenguer
We hypothesized that antiviral efficacy [sustained virologic response (SVR)] has improved in recent years in the transplant setting. Our aim was to assess whether the efficacy of pegylated interferon (PegIFN),ribavirin (Rbv) has improved over time. One hundred seven liver transplant patients [74% men, 55.5 years old (range: 37.5,69.5), 86% genotype 1a or 1b] were treated with PegIFN-Rbv for 355 (16,623) days at 20.1 (1.7,132.6) months after transplantation. Tacrolimus was used in 61%. Sixty-seven percent had baseline F3,F4 (cirrhosis: 20.5%). Donor age was 49 (12,78) years. SVR was achieved in 39 (36.5%) patients, with worse results achieved in recent years (2001,2003: n = 27, 46.5%; 2004: n = 23, 43.5%; 2005: n = 21, 35%; 2006 to January 2007: n = 36, 24%; P = 0.043). Variables associated with SVR in the univariate analysis included donor age, baseline viremia and cirrhosis, bilirubin levels, rapid virologic response and early virologic response (EVR), premature discontinuation of PegIFN or Rbv, and accumulated Rbv dose. In the multivariate analysis, the variables in the model were EVR [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.016,0.414, P = 0.002] and donor age (OR: 1.039, 95% CI: 1.008,1.071, P = 0.01). Variables that had changed over time included donor age, baseline viremia, disease severity (cirrhosis, baseline bilirubin, and leukocyte and platelet counts), interval between transplantation and therapy, and use of growth factors. In the multivariate analysis, variables independently changing were donor age (OR: 1.041, 95% CI: 1.013,1.071, P = 0.004), duration from transplantation to antiviral therapy (OR: 1.001, 95% CI: 1.000,1.001, P = 0.013), and baseline leukocyte count (OR: 1.000, 95% CI: 1.000,1.000, P = 0.034). In conclusion, the efficacy of antiviral therapy with PegIFN-Rbv has worsened over time, at least in our center. The increase in donor age and greater proportion of patients treated at advanced stages of disease are potential causes. Liver Transpl 15:738,746, 2009. © 2009 AASLD. [source]

Immunity, Homing and Efficacy of Allogeneic Adoptive Immunotherapy for Posttransplant Lymphoproliferative Disorders

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007
M. K. Gandhi
Adoptive immunotherapy using autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (auto-CTL) can regress posttransplant lymphoproliferative disorders (PTLD). Widespread applicability of auto-CTL remains constrained. Generation is time-consuming, and auto-CTL cannot be established in patients treated with the B-cell depleting antibody rituximab. By contrast, pregenerated allogeneic CTL (allo-CTL) offers immediate accessibility. Allo-CTL has previously shown efficacy in "early" polyclonal- PTLD. We treated three patients with aggressive, advanced monoclonal-PTLD following solid-organ transplantation. All were refractory to at least three prior therapies. Despite HLA disparity, there was negligible toxicity, with early in vivo antiviral efficacy and reconstitution of EBV peptide-specific immunity. Two patients attained complete remission (CR). One remains in CR 17 months following therapy, coincident with persistence of donor-derived tumor targeted EBV-specific CTL; the other died of non-PTLD related pathology. In the third patient, autopsy demonstrated homing of allo-CTL at the tumor site. Larger prospective studies of EBV-specific allo-CTL in PTLD are warranted. [source]