The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Naomi Givens - One of the best experts on this subject based on the ideXlab platform.

  • treatment emergent mutations and resistance in hiv infected children treated with Fosamprenavir containing antiretroviral regimens
    The Open Aids Journal, 2015
    Co-Authors: Lisa L Ross, Naomi Givens, Mark F Cotton, Haseena Cassim, Eugeny Voronin, Jorg Sievers, Katharine Cheng
    Abstract:

    Treatment-emergent mutations and drug resistance were analyzed in virus from HIV-infected children meeting virologic failure (VF) criteria over 48 weeks following treatment with unboosted Fosamprenavir or Fosamprenavir/ritonavir-containing regimens in studies APV20002 and APV29005. Both antiretroviral therapy (ART)-naive and ART-experienced patients were enrolled. Patients met VF criteria by either failing to suppress HIV-RNA to <400 copies/mL through week 24 or after confirmed viral rebound (≥400 copies/mL) anytime through week 48. Viral isolates were analyzed for treatment-emergent mutations or reduced drug susceptibility. Through week 48, 25/109 (23%) of APV29005 and 9/54 (17%) APV20002 study patients met VF. VF was more common in ART-experienced patients (68% and 78%, respectively). Major or minor treatment-emergent mutations were detected at VF in virus from 3 patients receiving unboosted Fosamprenavir-containing regimens and in virus from 10 patients receiving Fosamprenavir/ritonavir-containing regimens across the two studies. Major protease inhibitor mutations and the reverse transcriptase mutation M184V were detected at VF in virus from 4 and 5 patients, respectively, across both studies. Reduced drug susceptibility to any drug emerged in virus from 9 patients at VF, although reduced Fosamprenavir susceptibility emerged in virus from only 4 patients (2 ART-naive and 2 ART-experienced). No cross-resistance to the protease inhibitor darunavir was observed. In conclusion, given the high proportion of ART-experienced children (71%) in these two studies, the overall incidence of children meeting VF criteria through 48 weeks was relatively low (21%) and development of Fosamprenavir reduced drug susceptibility at VF was uncommon, further supporting the use of Fosamprenavir-containing ART regimens in HIV-infected children.

  • pharmacokinetics and 48 week safety and antiviral activity of Fosamprenavir containing regimens in hiv infected 2 to 18 year old children
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Claudia Fortuny, Susan L. Ford, Mary Beth Wire, Naomi Givens, Dan Duiculescu, Katharine Cheng, Harmony P Garges, Mark F Cotton, Desamparados Perez Tamarirt, Lisa L Ross
    Abstract:

    Background: pharmacokinetics, safety and antiviral activity of twice-daily Fosamprenavir with or without ritonavir were evaluated in 2- to 18-year-old protease inhibitor–naive and -experienced HIV-1–infected children. Methods: serial pharmacokinetic samples were collected at week 2 and predose samples every 4–12 weeks. safety and plasma HIV-1 RNA were monitored every 4–12 weeks. Results: twenty protease inhibitor–naive 2- to 48 weeks. twice-daily doses of Fosamprenavir/ritonavir 23/3 mg/kg in 2- to <6-year olds, 18/3 mg/kg in ≥6-year olds and 700/100 mg in adolescents achieved plasma amprenavir exposures comparable with or higher than 700/100 mg twice-daily in adults while Fosamprenavir 30 mg/ kg twice-daily in 2- to <6-year olds led to exposures higher than 1400 mg twice-daily in adults. the proportion of subjects with HIV-1 RNA <400 copies/mL at week 48 was 60% for Fosamprenavir and 53–74% for Fosamprenavir/ritonavir (intent-to-treat [exposed], snapshot analysis). Median increases in absolute and relative (percentage) CD4 counts from baseline to week 48 occurred in both the Fosamprenavir (340 cells/mm 3 ; 8%) and Fosamprenavir/ritonavir group (190 cells/mm 3; 8%). the most common adverse events were vomiting, cough, and diarrhea; 18 subjects experienced serious adverse events, including 9 with suspected abacavir hypersensitivity. Conclusions: Fosamprenavir regimens administered to HIV-1–infected children aged 2–18 years were generally well-tolerated and provided sustained antiviral activity over 48 weeks, with plasma amprenavir exposures comparable with or higher than adults.

  • pharmacokinetics safety and antiviral activity of Fosamprenavir ritonavir containing regimens in hiv infected children aged 4 weeks to 2 years 48 week study data
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Mark F Cotton, Susan L. Ford, Mary Beth Wire, Naomi Givens, Harmony P Garges, Lisa L Ross, Haseena Cassim, Noris Paviaruz, Teodora Perger, Yu Lou
    Abstract:

    Fosamprenavir (FPV) is the phosphate ester prodrug of the protease inhibitor (PI) amprenavir (APV), developed to improve the delivery of APV to adults and children. The safety and efficacy of FPV has been established in adults in 3 phase III studies, including FPV 1400 mg twice daily (BID) and FPV 1400 mg once daily (QD) + ritonavir (RTV) 200 mg QD in antiretroviral-naive adult subjects and FPV 700 mg BID + RTV 100 mg BID in PI-experienced adult subjects.1–3 FPV and FPV/RTV BID regimens have been established in children 2 to 18 years of age.4 This study, APV20002, evaluates the pharmacokinetics (PK), safety, tolerability and antiviral activity of FPV oral suspension administered with RTV in a BID regimen to PI-naive and PI-experienced subjects 4 weeks to <2 years of age. Recruitment commenced in October 2003 and completed in July 2010. The study is ongoing, and the 48-week data (data cutoff July 5, 2011) presented here include data up to and including the last subject reaching the week 48 visit.

  • long term safety study of Fosamprenavir containing regimens in hiv 1 infected patients
    Hiv Clinical Trials, 2013
    Co-Authors: Robin Wood, Joseph Gathe, Naomi Givens, Katharine Cheng, Sangeeta Sedani, Jorg Sievers
    Abstract:

    Background: Safety and efficacy of the protease inhibitor Fosamprenavir (FPV) ± ritonavir (r) was evaluated in 3 pivotal 48-week phase III studies. A follow-on study provides long-term data on FPV-...

  • impact of hiv subtype on response and resistance in antiretroviral naive adults comparing treatment with once daily versus twice daily ritonavir boosted Fosamprenavir in combination with abacavir lamivudine
    Drugs and Therapy Studies, 2011
    Co-Authors: Lisa L Ross, Giampiero Carosi, Adriano Lazzarin, H J Stellbrink, Graeme Moyle, Naomi Givens, Marjorie D Robinson, William G Nichols
    Abstract:

    The impact of HIV-1 subtype on resistance mutation selection and on virologic response to Fosamprenavir in combination with once-daily (QD) versus twice-daily (BID) dosing of ritonavir was examined in a prospective, open label, randomized study in antiretroviral-naive, HIV-1 infected subjects. We studied APV109141 compared QD Fosamprenavir/ritonavir (1400mg/100mg) to BID Fosamprenavir/ritonavir (700mg/100mg), administered in combination with a QD fixed-dose abacavir/lamivudine (600 mg/300 mg) combination tablet through 48 weeks in ART-naive subjects. HIV genotypes were obtained from all subjects at screen. Subjects with virologic failure (VF) were also genotyped at baseline and VF. HIV subtypes observed in the ITT (n=214) population were A or AE or AG circulating recombinant forms (CRFs) 19%; B 62%; BF or BG CRFs 2%; C or CPX CRFs 7%; D 2%; F1 7%; G 400 copies/mL through 48 weeks. Subtype appeared to have no preferential impact on virologic response or selection for specific resistance mutations in subjects receiving Fosamprenavir/ritonavir. Virologic failure rate was rare (3 subjects; each from different subtypes). At VF, virus from only one subject selected any HIV NRTI mutation (M184V); none selected major protease mutations.

Lisa L Ross - One of the best experts on this subject based on the ideXlab platform.

  • treatment emergent mutations and resistance in hiv infected children treated with Fosamprenavir containing antiretroviral regimens
    The Open Aids Journal, 2015
    Co-Authors: Lisa L Ross, Naomi Givens, Mark F Cotton, Haseena Cassim, Eugeny Voronin, Jorg Sievers, Katharine Cheng
    Abstract:

    Treatment-emergent mutations and drug resistance were analyzed in virus from HIV-infected children meeting virologic failure (VF) criteria over 48 weeks following treatment with unboosted Fosamprenavir or Fosamprenavir/ritonavir-containing regimens in studies APV20002 and APV29005. Both antiretroviral therapy (ART)-naive and ART-experienced patients were enrolled. Patients met VF criteria by either failing to suppress HIV-RNA to <400 copies/mL through week 24 or after confirmed viral rebound (≥400 copies/mL) anytime through week 48. Viral isolates were analyzed for treatment-emergent mutations or reduced drug susceptibility. Through week 48, 25/109 (23%) of APV29005 and 9/54 (17%) APV20002 study patients met VF. VF was more common in ART-experienced patients (68% and 78%, respectively). Major or minor treatment-emergent mutations were detected at VF in virus from 3 patients receiving unboosted Fosamprenavir-containing regimens and in virus from 10 patients receiving Fosamprenavir/ritonavir-containing regimens across the two studies. Major protease inhibitor mutations and the reverse transcriptase mutation M184V were detected at VF in virus from 4 and 5 patients, respectively, across both studies. Reduced drug susceptibility to any drug emerged in virus from 9 patients at VF, although reduced Fosamprenavir susceptibility emerged in virus from only 4 patients (2 ART-naive and 2 ART-experienced). No cross-resistance to the protease inhibitor darunavir was observed. In conclusion, given the high proportion of ART-experienced children (71%) in these two studies, the overall incidence of children meeting VF criteria through 48 weeks was relatively low (21%) and development of Fosamprenavir reduced drug susceptibility at VF was uncommon, further supporting the use of Fosamprenavir-containing ART regimens in HIV-infected children.

  • pharmacokinetics and 48 week safety and antiviral activity of Fosamprenavir containing regimens in hiv infected 2 to 18 year old children
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Claudia Fortuny, Susan L. Ford, Mary Beth Wire, Naomi Givens, Dan Duiculescu, Katharine Cheng, Harmony P Garges, Mark F Cotton, Desamparados Perez Tamarirt, Lisa L Ross
    Abstract:

    Background: pharmacokinetics, safety and antiviral activity of twice-daily Fosamprenavir with or without ritonavir were evaluated in 2- to 18-year-old protease inhibitor–naive and -experienced HIV-1–infected children. Methods: serial pharmacokinetic samples were collected at week 2 and predose samples every 4–12 weeks. safety and plasma HIV-1 RNA were monitored every 4–12 weeks. Results: twenty protease inhibitor–naive 2- to 48 weeks. twice-daily doses of Fosamprenavir/ritonavir 23/3 mg/kg in 2- to <6-year olds, 18/3 mg/kg in ≥6-year olds and 700/100 mg in adolescents achieved plasma amprenavir exposures comparable with or higher than 700/100 mg twice-daily in adults while Fosamprenavir 30 mg/ kg twice-daily in 2- to <6-year olds led to exposures higher than 1400 mg twice-daily in adults. the proportion of subjects with HIV-1 RNA <400 copies/mL at week 48 was 60% for Fosamprenavir and 53–74% for Fosamprenavir/ritonavir (intent-to-treat [exposed], snapshot analysis). Median increases in absolute and relative (percentage) CD4 counts from baseline to week 48 occurred in both the Fosamprenavir (340 cells/mm 3 ; 8%) and Fosamprenavir/ritonavir group (190 cells/mm 3; 8%). the most common adverse events were vomiting, cough, and diarrhea; 18 subjects experienced serious adverse events, including 9 with suspected abacavir hypersensitivity. Conclusions: Fosamprenavir regimens administered to HIV-1–infected children aged 2–18 years were generally well-tolerated and provided sustained antiviral activity over 48 weeks, with plasma amprenavir exposures comparable with or higher than adults.

  • pharmacokinetics safety and antiviral activity of Fosamprenavir ritonavir containing regimens in hiv infected children aged 4 weeks to 2 years 48 week study data
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Mark F Cotton, Susan L. Ford, Mary Beth Wire, Naomi Givens, Harmony P Garges, Lisa L Ross, Haseena Cassim, Noris Paviaruz, Teodora Perger, Yu Lou
    Abstract:

    Fosamprenavir (FPV) is the phosphate ester prodrug of the protease inhibitor (PI) amprenavir (APV), developed to improve the delivery of APV to adults and children. The safety and efficacy of FPV has been established in adults in 3 phase III studies, including FPV 1400 mg twice daily (BID) and FPV 1400 mg once daily (QD) + ritonavir (RTV) 200 mg QD in antiretroviral-naive adult subjects and FPV 700 mg BID + RTV 100 mg BID in PI-experienced adult subjects.1–3 FPV and FPV/RTV BID regimens have been established in children 2 to 18 years of age.4 This study, APV20002, evaluates the pharmacokinetics (PK), safety, tolerability and antiviral activity of FPV oral suspension administered with RTV in a BID regimen to PI-naive and PI-experienced subjects 4 weeks to <2 years of age. Recruitment commenced in October 2003 and completed in July 2010. The study is ongoing, and the 48-week data (data cutoff July 5, 2011) presented here include data up to and including the last subject reaching the week 48 visit.

  • evaluation of cardiovascular biomarkers in a randomized trial of Fosamprenavir ritonavir vs efavirenz with abacavir lamivudine in underrepresented antiretroviral naive hiv infected patients support 96 week results
    BMC Infectious Diseases, 2013
    Co-Authors: Princy Kumar, Franco Felizarta, Edwin Dejesus, Lisa L Ross, Gregory D Huhn, Louis Sloan, Catherine B Small, Howard Edelstein, Ritche Hao, Britt Stancil
    Abstract:

    Rates of cardiovascular disease are higher among HIV-infected patients as a result of the complex interplay between traditional risk factors, HIV-related inflammatory and immunologic changes, and effects of antiretroviral therapy (ART). This study prospectively evaluated changes in cardiovascular biomarkers in an underrepresented, racially diverse, HIV-1-infected population receiving abacavir/lamivudine as backbone therapy. This 96-week, open-label, randomized, multicenter study compared once-daily Fosamprenavir/ritonavir 1400/100 mg and efavirenz 600 mg, both with ABC/3TC 600 mg/300 mg, in antiretroviral-naive, HLA-B*5701-negative adults without major resistance mutations to study drugs. We evaluated changes from baseline to weeks 4, 12, 24, 48, and 96 in interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), d-dimer, plasminogen, and fibrinogen. Biomarker data were log-transformed before analysis, and changes from baseline were described using geometric mean ratios. This study enrolled 101 patients (51 receiving Fosamprenavir/ritonavir; 50 receiving efavirenz): 32% female, 60% African American, and 38% Hispanic/Latino; 66% (67/101) completed 96 weeks on study. At week 96, levels of IL-6, sVCAM-1, d-dimer, fibrinogen, and plasminogen were lower than baseline in both treatment groups, and the decrease was statistically significant for sVCAM-1 (Fosamprenavir/ritonavir and efavirenz), d-dimer (Fosamprenavir/ritonavir and efavirenz), fibrinogen (efavirenz), and plasminogen (efavirenz). Values of hs-CRP varied over time in both groups, with a significant increase over baseline at Weeks 4 and 24 in the efavirenz group. At week 96, there was no difference between the groups in the percentage of patients with HIV-1 RNA <50 copies/mL (Fosamprenavir/ritonavir 63%; efavirenz 66%) by ITT missing-equals-failure analysis. Treatment-related grade 2–4 adverse events were more common with efavirenz (32%) compared with Fosamprenavir/ritonavir (20%), and median lipid concentrations increased in both groups over 96 weeks of treatment. In this study of underrepresented patients, treatment with abacavir/lamivudine combined with either Fosamprenavir/ritonavir or efavirenz over 96 weeks, produced stable or declining biomarker levels except for hs-CRP, including significant and favorable decreases in thrombotic activity (reflected by d-dimer) and endothelial activation (reflected by sVCAM-1). Our study adds to the emerging data that some cardiovascular biomarkers are decreased with initiation of ART and control of HIV viremia. ClinicalTrials.gov identifier NCT00727597

  • impact of hiv subtype on response and resistance in antiretroviral naive adults comparing treatment with once daily versus twice daily ritonavir boosted Fosamprenavir in combination with abacavir lamivudine
    Drugs and Therapy Studies, 2011
    Co-Authors: Lisa L Ross, Giampiero Carosi, Adriano Lazzarin, H J Stellbrink, Graeme Moyle, Naomi Givens, Marjorie D Robinson, William G Nichols
    Abstract:

    The impact of HIV-1 subtype on resistance mutation selection and on virologic response to Fosamprenavir in combination with once-daily (QD) versus twice-daily (BID) dosing of ritonavir was examined in a prospective, open label, randomized study in antiretroviral-naive, HIV-1 infected subjects. We studied APV109141 compared QD Fosamprenavir/ritonavir (1400mg/100mg) to BID Fosamprenavir/ritonavir (700mg/100mg), administered in combination with a QD fixed-dose abacavir/lamivudine (600 mg/300 mg) combination tablet through 48 weeks in ART-naive subjects. HIV genotypes were obtained from all subjects at screen. Subjects with virologic failure (VF) were also genotyped at baseline and VF. HIV subtypes observed in the ITT (n=214) population were A or AE or AG circulating recombinant forms (CRFs) 19%; B 62%; BF or BG CRFs 2%; C or CPX CRFs 7%; D 2%; F1 7%; G 400 copies/mL through 48 weeks. Subtype appeared to have no preferential impact on virologic response or selection for specific resistance mutations in subjects receiving Fosamprenavir/ritonavir. Virologic failure rate was rare (3 subjects; each from different subtypes). At VF, virus from only one subject selected any HIV NRTI mutation (M184V); none selected major protease mutations.

Yu Lou - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics safety and antiviral activity of Fosamprenavir ritonavir containing regimens in hiv infected children aged 4 weeks to 2 years 48 week study data
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Mark F Cotton, Susan L. Ford, Mary Beth Wire, Naomi Givens, Harmony P Garges, Lisa L Ross, Haseena Cassim, Noris Paviaruz, Teodora Perger, Yu Lou
    Abstract:

    Fosamprenavir (FPV) is the phosphate ester prodrug of the protease inhibitor (PI) amprenavir (APV), developed to improve the delivery of APV to adults and children. The safety and efficacy of FPV has been established in adults in 3 phase III studies, including FPV 1400 mg twice daily (BID) and FPV 1400 mg once daily (QD) + ritonavir (RTV) 200 mg QD in antiretroviral-naive adult subjects and FPV 700 mg BID + RTV 100 mg BID in PI-experienced adult subjects.1–3 FPV and FPV/RTV BID regimens have been established in children 2 to 18 years of age.4 This study, APV20002, evaluates the pharmacokinetics (PK), safety, tolerability and antiviral activity of FPV oral suspension administered with RTV in a BID regimen to PI-naive and PI-experienced subjects 4 weeks to <2 years of age. Recruitment commenced in October 2003 and completed in July 2010. The study is ongoing, and the 48-week data (data cutoff July 5, 2011) presented here include data up to and including the last subject reaching the week 48 visit.

  • steady state pharmacokinetics cord blood concentrations and safety of ritonavir boosted Fosamprenavir in pregnancy
    Journal of Acquired Immune Deficiency Syndromes, 2013
    Co-Authors: Michelle S Cespedes, Susan L. Ford, Yu Lou, Gary E Pakes, Delivette Castor, Doreen Lee, Judith A Aberg
    Abstract:

    Steady-state pharmacokinetics in pregnant women prescribed ritonavir-boosted Fosamprenavir (FPV) to prevent HIV transmission were assessed in the second trimester, third trimester, and postpartum. Compared with postpartum, geometric mean amprenavir (APV, FPVs active metabolite) area under the plasma concentration-time curves were 35% lower in the second trimester and 25% lower in the third trimester. Maternal APV concentrations were 9- to 15-fold above the mean APV protein-adjusted 50% inhibitory concentration for wild-type HIV. Median ratio of cord blood/maternal APV levels was 0.27, and all infants were HIV negative. FPV/ritonavir during pregnancy was well tolerated and led to virologic suppression.

  • Fosamprenavir ritonavir in advanced hiv disease triad a randomized study of high dose dual boosted or standard dose Fosamprenavir ritonavir in hiv 1 infected patients with antiretroviral resistance
    Journal of Antimicrobial Chemotherapy, 2009
    Co-Authors: Jeanmichel Molina, Gilles Pialoux, Mary Beth Wire, Mounir Aitkhaled, Roberto Cauda, Vicente Soriano, Roberto Rinaldi, Giovanni Penco, Jeanguy Baril, Yu Lou
    Abstract:

    Results: There was no difference in the week 24 AAUCMB between the regimens. The proportion of patients with <50 copies/mL of plasma HIV RNA was 21%, 24% and 20%, respectively, by time to loss of virological response (TLOVR) analysis. High baseline drug resistance provided some explanation for the low efficacy. A lower baseline background drug resistance and higher Fosamprenavir genotypic inhibitory quotient led to better antiviral responses. The plasma amprenavir trough concentartion (Ct) was 49% higher in the HD-FPV/RTV arm than in the STD-FPV/RTV arm and similar in the FPV/LPV/RTV and STD-FPV/RTV arms. The plasma lopinavir Ct was similar to historical data with standard LPV/RTV 400 mg/100 mg twice daily. All regimens were relatively well tolerated, although diarrhoea was more frequent in the HD-FPV/RTV and FPV/LPV/RTV arms, and hypertriglyceridaemia and increased total cholesterol were more common in the FPV/LPV/RTV arm. Conclusions: While the strategies of higher dose FPV/RTV and dual FPV/LPV/RTV were relevant at the time of study initiation, new therapies for antiretroviral-experienced patients make such strategies of

  • pharmacokinetic interaction between Fosamprenavir ritonavir and rifabutin in healthy subjects
    Antimicrobial Agents and Chemotherapy, 2008
    Co-Authors: Susan L. Ford, Yu Lou, Julie Borland, Geoffrey J. Yuen, Yachi Chen, Sherene S Min, Mark J. Shelton
    Abstract:

    Rifabutin (RFB) is administered for treatment of tuberculosis and Mycobacterium avium complex infection, including use for patients coinfected with human immunodeficiency virus (HIV). Increased systemic exposure to RFB and its equipotent active metabolite, 25- O -desacetyl-RFB (dAc-RFB), has been reported during concomitant administration of CYP3A4 inhibitors, including ritonavir (RTV), lopinavir, and amprenavir (APV); therefore, a reduction in the RFB dosage is recommended when it is coadministered with these protease inhibitors. Fosamprenavir (FPV), the phosphate ester prodrug of the HIV type 1 protease inhibitor APV, is administered either with or without RTV. A randomized, open-label, two-period, two-sequence, balanced, crossover drug interaction study was conducted with 22 healthy adult subjects to compare steady-state plasma RFB pharmacokinetic parameters during concomitant administration of FPV-RTV (700/100 mg twice a day [BID]) with a 75%-reduced RFB dose (150 mg every other day [QOD]) to the standard RFB regimen (300 mg once per day [QD]) by geometric least-squares mean ratios. Relative to results with RFB (300 mg QD), coadministration of dose-adjusted RFB with FPV-RTV resulted in an unchanged RFB area under the concentration-time curve for 0 to 48 h (AUC 0-48 ) and a 14% decrease in the maximum concentration of drug in plasma ( C max ), whereas the AUC 0-48 and C max of dAc-RFB were increased by 11- and 6-fold, respectively, resulting in a 64% increase in the total antimycobacterial AUC 0-48 . Relative to historical controls, the plasma APV AUC from 0 h to the end of the dosing interval (AUC 0-τ ) and C max were increased ∼35%, and the concentration at the end of the dosing interval at steady state was unchanged following coadministration of RFB with FPV-RTV. The safety profile of the combination of RFB and FPV-RTV was consistent with previously described events with RFB or FPV-RTV alone. Based on the results of this study, a reduction in the RFB dose by ≥75% (to 150 mg QOD or three times per week) is recommended when it is coadministered with FPV-RTV (700/100 mg BID).

  • Fosamprenavir plus Ritonavir Increases Plasma Ketoconazole and Ritonavir Exposure, while Amprenavir Exposure Remains Unchanged
    Antimicrobial agents and chemotherapy, 2007
    Co-Authors: Mary Beth Wire, Yu Lou, Charles H. Ballow, Julie Borland, Mark J. Shelton, Geoffrey J. Yuen, Jiang Lin, Eric Lewis
    Abstract:

    Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV) pharmacokinetics were evaluated in 15 healthy subjects after being treated with KETO at 200 mg once daily (QD), Fosamprenavir (FPV)/RTV at 700/100 mg twice daily (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open-label study. The KETO area under the concentration-time curve at steady state was increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure was slightly increased.

Mary Beth Wire - One of the best experts on this subject based on the ideXlab platform.

  • population pharmacokinetic modeling and simulation of amprenavir following Fosamprenavir ritonavir administration for dose optimization in hiv infected pediatric patients
    The Journal of Clinical Pharmacology, 2014
    Co-Authors: April M Barbour, Leonid Gibiansky, Mary Beth Wire
    Abstract:

    Fosamprenavir (FPV) is the phosphate ester prodrug of the HIV-1 protease inhibitor amprenavir (APV). A pediatric population pharmacokinetic model for APV was developed and simulation was used to identify dosing regimens for pediatric patients receiving FPV in combination with ritonavir (RTV) which resulted in concentrations similar to those in adults receiving FPV/RTV 700/100 mg BID. Pharmacokinetic data was obtained from HIV infected subjects aged 2 months to 18 years receiving either FPV or FPV/RTV. A two-compartment model with first order absorption and elimination was an appropriate structural model. Significant covariates in the model included RTV coadministration on clearance, fed status on bioavailability for the oral suspension, body weight on clearance and volume terms, black race on clearance, and age on clearance. The following FPV/RTV twice daily dosing regimens in pediatric patients delivered plasma APV exposure similar to adults: 45/7 mg/kg in patients weighing <11 kg, 30/3 mg/kg in patients weighing 11 to <15 kg, 23/3 mg/kg in patients weighing 15 to <20 kg, and 18/3 mg/kg in patients weighting ≥20 kg. Additionally children weighing ≥39 kg can receive the adult regimen.

  • pharmacokinetics and 48 week safety and antiviral activity of Fosamprenavir containing regimens in hiv infected 2 to 18 year old children
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Claudia Fortuny, Susan L. Ford, Mary Beth Wire, Naomi Givens, Dan Duiculescu, Katharine Cheng, Harmony P Garges, Mark F Cotton, Desamparados Perez Tamarirt, Lisa L Ross
    Abstract:

    Background: pharmacokinetics, safety and antiviral activity of twice-daily Fosamprenavir with or without ritonavir were evaluated in 2- to 18-year-old protease inhibitor–naive and -experienced HIV-1–infected children. Methods: serial pharmacokinetic samples were collected at week 2 and predose samples every 4–12 weeks. safety and plasma HIV-1 RNA were monitored every 4–12 weeks. Results: twenty protease inhibitor–naive 2- to 48 weeks. twice-daily doses of Fosamprenavir/ritonavir 23/3 mg/kg in 2- to <6-year olds, 18/3 mg/kg in ≥6-year olds and 700/100 mg in adolescents achieved plasma amprenavir exposures comparable with or higher than 700/100 mg twice-daily in adults while Fosamprenavir 30 mg/ kg twice-daily in 2- to <6-year olds led to exposures higher than 1400 mg twice-daily in adults. the proportion of subjects with HIV-1 RNA <400 copies/mL at week 48 was 60% for Fosamprenavir and 53–74% for Fosamprenavir/ritonavir (intent-to-treat [exposed], snapshot analysis). Median increases in absolute and relative (percentage) CD4 counts from baseline to week 48 occurred in both the Fosamprenavir (340 cells/mm 3 ; 8%) and Fosamprenavir/ritonavir group (190 cells/mm 3; 8%). the most common adverse events were vomiting, cough, and diarrhea; 18 subjects experienced serious adverse events, including 9 with suspected abacavir hypersensitivity. Conclusions: Fosamprenavir regimens administered to HIV-1–infected children aged 2–18 years were generally well-tolerated and provided sustained antiviral activity over 48 weeks, with plasma amprenavir exposures comparable with or higher than adults.

  • pharmacokinetics safety and antiviral activity of Fosamprenavir ritonavir containing regimens in hiv infected children aged 4 weeks to 2 years 48 week study data
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Mark F Cotton, Susan L. Ford, Mary Beth Wire, Naomi Givens, Harmony P Garges, Lisa L Ross, Haseena Cassim, Noris Paviaruz, Teodora Perger, Yu Lou
    Abstract:

    Fosamprenavir (FPV) is the phosphate ester prodrug of the protease inhibitor (PI) amprenavir (APV), developed to improve the delivery of APV to adults and children. The safety and efficacy of FPV has been established in adults in 3 phase III studies, including FPV 1400 mg twice daily (BID) and FPV 1400 mg once daily (QD) + ritonavir (RTV) 200 mg QD in antiretroviral-naive adult subjects and FPV 700 mg BID + RTV 100 mg BID in PI-experienced adult subjects.1–3 FPV and FPV/RTV BID regimens have been established in children 2 to 18 years of age.4 This study, APV20002, evaluates the pharmacokinetics (PK), safety, tolerability and antiviral activity of FPV oral suspension administered with RTV in a BID regimen to PI-naive and PI-experienced subjects 4 weeks to <2 years of age. Recruitment commenced in October 2003 and completed in July 2010. The study is ongoing, and the 48-week data (data cutoff July 5, 2011) presented here include data up to and including the last subject reaching the week 48 visit.

  • similar virologic and immunologic efficacy with Fosamprenavir boosted with 100 mg or 200 mg of ritonavir in hiv infected patients results of the less trial
    Hiv Clinical Trials, 2010
    Co-Authors: Calvin J Cohen, Mary Beth Wire, Benjamin Young, Edwin Dejesus, Cindy Vavro, Anthony Lamarca, Linda Yau, Lisa G Patel, Paul Wannamaker, Mark S Shaefer
    Abstract:

    AbstractPurpose: Ritonavir (RTV) effectively boosts most protease inhibitors but is associated with significant dose-dependent adverse events (AEs). In an effort to better manage toxicities through a reduced dose of RTV, this study compared Fosamprenavir (FPV) boosted with RTV 100 mg (FPV/r100) or with RTV 200 mg (FPV/r200) daily. Methods: This 24-week, open-label study enrolled patients taking a FPV/r200-containing regimen who had HIV RNA <400 copies/mL and randomized them 1:2 to continue that regimen or simplify to FPV/r100 once daily. Other medications were not altered. The primary endpoint was the percentage of patients without suspected or confirmed virologic failure (HIV RNA ≥400 copies/mL) through week 24 by a missing/discontinuation equals failure (M/D=F) analysis. Noninferiority criteria were demonstrated if the lower bound of the 95% confidence interval (CI) for the difference in the primary endpoint rates between groups was greater than −12. Results: The 2 regimens met prespecified noninferiori...

  • Fosamprenavir ritonavir in advanced hiv disease triad a randomized study of high dose dual boosted or standard dose Fosamprenavir ritonavir in hiv 1 infected patients with antiretroviral resistance
    Journal of Antimicrobial Chemotherapy, 2009
    Co-Authors: Jeanmichel Molina, Gilles Pialoux, Mary Beth Wire, Mounir Aitkhaled, Roberto Cauda, Vicente Soriano, Roberto Rinaldi, Giovanni Penco, Jeanguy Baril, Yu Lou
    Abstract:

    Results: There was no difference in the week 24 AAUCMB between the regimens. The proportion of patients with <50 copies/mL of plasma HIV RNA was 21%, 24% and 20%, respectively, by time to loss of virological response (TLOVR) analysis. High baseline drug resistance provided some explanation for the low efficacy. A lower baseline background drug resistance and higher Fosamprenavir genotypic inhibitory quotient led to better antiviral responses. The plasma amprenavir trough concentartion (Ct) was 49% higher in the HD-FPV/RTV arm than in the STD-FPV/RTV arm and similar in the FPV/LPV/RTV and STD-FPV/RTV arms. The plasma lopinavir Ct was similar to historical data with standard LPV/RTV 400 mg/100 mg twice daily. All regimens were relatively well tolerated, although diarrhoea was more frequent in the HD-FPV/RTV and FPV/LPV/RTV arms, and hypertriglyceridaemia and increased total cholesterol were more common in the FPV/LPV/RTV arm. Conclusions: While the strategies of higher dose FPV/RTV and dual FPV/LPV/RTV were relevant at the time of study initiation, new therapies for antiretroviral-experienced patients make such strategies of

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  • Fosamprenavir ritonavir in advanced hiv disease triad a randomized study of high dose dual boosted or standard dose Fosamprenavir ritonavir in hiv 1 infected patients with antiretroviral resistance
    Journal of Antimicrobial Chemotherapy, 2009
    Co-Authors: Jeanmichel Molina, Gilles Pialoux, Mary Beth Wire, Mounir Aitkhaled, Roberto Cauda, Vicente Soriano, Roberto Rinaldi, Giovanni Penco, Jeanguy Baril, Yu Lou
    Abstract:

    Results: There was no difference in the week 24 AAUCMB between the regimens. The proportion of patients with <50 copies/mL of plasma HIV RNA was 21%, 24% and 20%, respectively, by time to loss of virological response (TLOVR) analysis. High baseline drug resistance provided some explanation for the low efficacy. A lower baseline background drug resistance and higher Fosamprenavir genotypic inhibitory quotient led to better antiviral responses. The plasma amprenavir trough concentartion (Ct) was 49% higher in the HD-FPV/RTV arm than in the STD-FPV/RTV arm and similar in the FPV/LPV/RTV and STD-FPV/RTV arms. The plasma lopinavir Ct was similar to historical data with standard LPV/RTV 400 mg/100 mg twice daily. All regimens were relatively well tolerated, although diarrhoea was more frequent in the HD-FPV/RTV and FPV/LPV/RTV arms, and hypertriglyceridaemia and increased total cholesterol were more common in the FPV/LPV/RTV arm. Conclusions: While the strategies of higher dose FPV/RTV and dual FPV/LPV/RTV were relevant at the time of study initiation, new therapies for antiretroviral-experienced patients make such strategies of

  • study of once daily versus twice daily Fosamprenavir plus ritonavir administered with abacavir lamivudine once daily in antiretroviral naive hiv 1 infected adult subjects
    Hiv Clinical Trials, 2009
    Co-Authors: Giampiero Carosi, Schlomo Staszewski, Adriano Lazzarin, H J Stellbrink, Graeme Moyle, Sorin Rugina, Naomi Givens, L Ross, Catherine Granier, Mounir Aitkhaled
    Abstract:

    AbstractPurpose: Fosamprenavir/ritonavir 1400 mg/100 mg once-daily regimen may have a more favourable tolerability and lipid profile than the Fosamprenavir/ritonavir twice-daily regimen, while maintaining comparable antiviral efficacy. Methods: This open-label study had a group-sequential design with a stage 1 Week 24 futility analysis, with both efficacy and safety go-criteria for progression to stage 2. There were 214 antiretroviral-naive, HIV-1–infected subjects who were randomised to receive either Fosamprenavir/ritonavir 1400 mg/100 mg once daily or Fosamprenavir/ ritonavir 700 mg/100 mg twice daily, both with abacavir/lamivudine fixed-dose combination tablet. Primary endpoints were the proportion of subjects achieving HIV-1 RNA <400 copies/mL at Week 48 and the mean change from baseline in fasting non-HDL cholesterol. Results: Though stage 1 futility analysis did not meet criteria for progression to stage 2, subjects enrolled in stage 1 were followed to Week 48 per protocol. At Week 48, noninferior ...