97 research outputs found
<b>Supplemental Material - EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B</b>
No full textSupplementary Material for EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B by Jordan J Feld, Eric Lawitz, Tuan Nguyen, Jacob Lalezari, Tarek Hassanein, Paul Martin, Steven-Huy Han, Douglas Dieterich, Jeanne-Marie Giard, Guy De La Rosa, Alaa Ahmad, Ed Luo, Annie L Conery, and Nathalie Adda in Antiviral Therapy.</p
Quantification of zidovudine and individual zidovudine phosphates in peripheral blood mononuclear cells by a combined isocratic high performance liquid chromatography radioimmunoassay method
No full textAn Open-Label Safety Study of Enfuvirtide Injection with a Needle-Free Injection Device or Needle/Syringe: The Biojector 2000 Open-Label Safety Study (BOSS)
No full textRestoration of blood total glutathione status and lymphocyte function following α-lipoic acid supplementation in patients with HIV infection
No full textObjectives: To determine whether supplementation with α-lipoic acid (ALA), a glutathione-replenishing disulfide, modulates whole blood total glutathione (GSH+GSSG) levels and improves lymphocyte function in human immunodeficiency virus (HIV)-infected subjects with history of unresponsiveness to highly active antiretroviral treatment (HAART). Design and setting: Randomized, double-blinded, placebo-controlled trial conducted at two study sites: an eye clinic at a county hospital in San Jose and a research clinic in San Francisco, California. Subjects: A total of 33 HIV-infected men and women with viral load \u3e 10,000 copies/cm3, despite HAART, aged 4447 years, approximately 36% nonwhite, were enrolled. Intervention: Patients were randomly assigned to receive either ALA (300 mg three times a day) or matching placebo for 6 months. Main outcome measures: The change over 6 months in blood total glutathione status, lymphocyte proliferation response to T-cell mitogens, CD4 cell count, and viral load in patients receiving ALA compared to placebo. Results: The mean blood total glutathione level in ALA-supplemented subjects was significantly elevated after 6 months (1.34 ± 0.79 vs. 0.81 ± 0.18 mmol/L) compared to insignificant change (0.76 ± 0.34 vs. 0.76 ± 0.22 mmol/L) in the placebo group (ALA vs. placebo: p = 0.04). The lymphocyte proliferation response was significantly enhanced or stabilized after 6 months of ALA supplementation compared to progressive decline in the placebo group (ALA vs. placebo: p \u3c 0.001 with phytohemagglutinin; p = 0.02 with anti-CD3 monoclonal antibody). A positive correlation was seen between blood total glutathione level and lymphocyte response to anti-CD3 stimulation (R 2 = 0.889). There was no significant change in either HIV RNA level or CD4 count over 6 months in the ALA-supplemented compared to the control group. Conclusion: Supplementation with α-lipoic acid may positively impact patients with HIV and acquired immune deficiency syndrome by restoring blood total glutathione level and improving functional reactivity of lymphocytes to T-cell mitogens. © 2008 Mary Ann Liebert, Inc
A Preclinical and Clinical Overview of the Nucleotide-Based Antiviral Agent Cidofovir (HPMPC)
No full textPharmacokinetics of once-daily Etravirine without and with Once-daily Darunavir/ritonavir in Antiretroviral-Naive HIV type-1-Infected Adults
No full textBackground A pharmacokinetic trial was conducted to evaluate the potential for once-daily etravirine in anti-retroviral regimens without and with darunavir/ritonavir. Methods During this multicentre, open-label, Phase IIa trial, treatment-naive patients aged ≥18 years with HIV type-1 (HIV-1) received etravirine 400 mg once daily with tenofovir disoproxil fumarate/emtricitabine 300/200 mg once daily from days 1–14; on days 15–28, darunavir/ritonavir 800/100 mg once daily was added. On day 29, etravirine was discontinued and patients continued with the other medications to day 42. Serial blood sampling for etravirine pharmacokinetics was performed over 24 h on day 14 and 28; patients fasted for ≥10 h prior to these visits. Results Of 23 enrolled patients (male 87%, Caucasian 39%), pharmacokinetic profiles for etravirine were available for 21 and 20 patients on day 14 and 28, respectively. The plasma concentration–time profile and pharmacokinetics for etravirine were unchanged with or without darunavir/ritonavir. The mean maximum plasma concentration (Cmax) was reached 4 h after administration and was 790 and 801 ng/ml on day 14 and 28, respectively; mean area under the plasma concentration–time curve (AUC) from before administration to 24 h after administration was 10,410 ng•h/ml on day 14 and 10,720 ng•h/ml on day 28. In a post-hoc analysis, etravirine Cmax was higher, minimum plasma concentration was lower and AUC was similar when compared with etravirine 200 mg twice daily. Conclusions Addition of darunavir/ritonavir to etravirine, all dosed once daily, did not have a clinically significant effect on the pharmacokinetics of etravirine. Findings support further investigation of etravirine 400 mg once daily in HIV-1-infected patients. (Trial registration number NCT00534352.) </jats:sec
Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: End-of-study analysis of a Phase III randomized trial
No full textThe observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received ≥ 1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection
Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine
No full textBackground & AimsHepatitis C virus (HCV)-infected patients with a history of injection drug use have low rates of initiation and completion of interferon-based therapies. This study evaluated efficacy, safety, and pharmacokinetics of a 12-week all-oral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir+ribavirin in HCV genotype 1-infected patients on stable opioid replacement therapy.MethodsThis was a phase II, multicenter, open-label, single-arm study in treatment-naïve or peginterferon/ribavirin treatment-experienced HCV genotype 1-infected patients on methadone or buprenorphine±naloxone. Patients received 12weeks of co-formulated ombitasvir/paritaprevir/ritonavir (25mg/150mg/100mg once daily) and dasabuvir (250mg twice daily)+weight-based ribavirin. The primary efficacy endpoint was sustained virologic response 12weeks post-treatment.ResultsThirty-eight non-cirrhotic patients on chronic methadone (n=19) or buprenorphine (n=19) were enrolled. A total of 37 patients (97.4%) had a sustained virologic response 12weeks post-treatment. No patient had a viral breakthrough or relapse. One patient discontinued due to serious adverse events unrelated to study drug (cerebrovascular accident and sarcoma). The most frequent adverse events were nausea, fatigue, and headache. Eight patients had on-treatment hemoglobin concentrations <10g/dl. Pharmacokinetic analyses indicated no clinically meaningful impact of methadone or buprenorphine on ombitasvir, paritaprevir, ritonavir, dasabuvir, or dasabuvir M1 metabolite exposures. No dose adjustments of methadone or buprenorphine were required.ConclusionsThe interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir+ribavirin for 12weeks was well tolerated and achieved sustained virologic response in 97.4% of patients on opioid substitution therapy in this study. This all-oral regimen may provide an effective alternative to interferon-based therapies for HCV-infected patients with a history of injection drug use
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