20 results on '"Sings HL"'
Search Results
2. Anemia during treatment with peginterferon Alfa-2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial
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Sulkowski, M, Poordad, F, Manns, M, Bronowicki, J, Rajender Reddy, K, Harrison, S, Afdhal, N, Sings, H, Pedicone, L, Koury, K, Sniukiene, V, Burroughs, M, Albrecht, J, Brass, C, Jacobson, I, Sprint, 2ti, Angelico, M, UL, NGERE, Johns Hopkins University School of Medicine [Baltimore], Cedars-Sinai Medical Center, Hannover Medical School [Hannover] (MHH), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Pennsylvania, Brooke Army Medical Center (BAMC), Beth Israel Medical Centre, Merck & Co. Inc, Weill Medical College of Cornell University [New York], University of Pennsylvania [Philadelphia], Gerken, Guido (Beitragende*r), Schlaak, Jörg Friedrich (Beitragende*r), Sulkowski, MS, Poordad, F, Manns, MP, Bronowicki, JP, Rajender Reddy, K, Harrison, SA, Afdhal, NH, Sings, HL, Pedicone, LD, Koury, KJ, Sniukiene, V, Burroughs, MH, Albrecht, JK, Brass, CA, Jacobson, IM, Craxi, A, and SPRINT-2 Trial Investigators
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Male ,[SDV]Life Sciences [q-bio] ,Medizin ,Gastroenterology ,Polyethylene Glycols ,Placebos ,chemistry.chemical_compound ,Hemoglobins ,0302 clinical medicine ,hemic and lymphatic diseases ,Medicine ,030212 general & internal medicine ,Chronic ,Settore MED/12 - Gastroenterologia ,Interferon-alpha ,Serine Proteinase Inhibitors ,Proline ,Recombinant Proteins ,Hematinics ,Humans ,Ribavirin ,Anemia ,Antiviral Agents ,Drug Therapy, Combination ,Erythropoietin ,Adult ,Treatment Outcome ,Hepatitis C, Chronic ,Female ,Hepatitis C ,3. Good health ,[SDV] Life Sciences [q-bio] ,Combination ,Peginterferon alfa-2b ,030211 gastroenterology & hepatology ,medicine.drug ,medicine.medical_specialty ,Interferon alpha-2 ,Placebo ,protease inhibitor ,03 medical and health sciences ,Drug Therapy ,Internal medicine ,Boceprevir ,Adverse effect ,Hepatology ,business.industry ,medicine.disease ,Surgery ,chemistry ,business - Abstract
International audience; Boceprevir (BOC) added to peginterferon alfa-2b (PegIFN) and ribavirin (RBV) significantly increases sustained virologic response (SVR) rates over PegIFN/RBV alone in previously untreated adults with chronic hepatitis C genotype 1. We evaluate the relationship of incident anemia with triple therapy. A total of 1,097 patients received a 4-week lead-in of PegIFN/RBV followed by: (1) placebo plus PegIFN/RBV for 44 weeks (PR48); (2) BOC plus PegIFN/RBV using response-guided therapy (BOC/RGT); and (3) BOC plus PegIFN/RBV for 44 weeks (BOC/PR48). The management of anemia (hemoglobin [Hb]
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- 2013
3. Factors that predict response of patients with hepatitis C virus infection to boceprevir
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Poordad, Fred, Bronowicki, Jeanpierre, Gordon, Stuart C., Zeuzem, Stefan, Jacobson, Ira M., Sulkowski, Mark S., Poynard, Thierry, Morgan, Timothy R., Molony, Cliona, Pedicone, Lisa D., Sings, Heather L., Burroughs, Margaret H., Sniukiene, Vilma, Boparai, Navdeep, Goteti, Venkata S., Brass, Clifford A., Albrecht, Janice K., Bacon, Bruce R., Sprint, 2, Respond, 2 Investigators, Taliani, Gloria, Cedars-Sinai Medical Center, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Université Henri Poincaré - Nancy 1 (UHP), Henry Ford Hospital, Goethe-University Frankfurt am Main, Weill Medical College of Cornell University [New York], California State University [Long Beach] (CSULB ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Merck & Co. Inc, Saint Louis University (SLU), Hepatology and Liver Transplantation, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Johann Wolfgang Goethe University Medical Center, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Poordad, F, Bronowicki, JP, Gordon, SC, Zeuzem, S, Jacobson, IM, Sulkowski, MS, Poynard, T, Morgan, TR, Molony, C, Pedicone, LD, Sings, HL, Burroughs, MH, Sniukiene, V, Boparai, N, Goteti, VS, Brass, CA, Albrecht, JK, Bacon, BR, Craxi, A, and SPRINT-2 and RESPOND-2 Investigators
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Male ,Cirrhosis ,MESH: Logistic Models ,Hepacivirus ,MESH: Risk Assessment ,Gastroenterology ,Polyethylene Glycols ,MESH: Recombinant Proteins ,MESH: Genotype ,0302 clinical medicine ,Odds Ratio ,Prospective Studies ,MESH: Treatment Outcome ,Response to Therapy ,0303 health sciences ,MESH: Polymorphism, Single Nucleotide ,virus diseases ,3. Good health ,MESH: RNA, Viral ,HCV ,Drug Therapy, Combination ,030211 gastroenterology & hepatology ,Clinical Trial ,Genetic ,Prognostic Factors ,Adult ,Antiviral Agents ,Biomarkers ,Canada ,Europe ,Female ,Genotype ,Hepatitis C ,Humans ,Interferon-alpha ,Interleukins ,Logistic Models ,Multivariate Analysis ,Phenotype ,Polymorphism, Single Nucleotide ,Proline ,RNA, Viral ,Recombinant Proteins ,Ribavirin ,Risk Assessment ,Risk Factors ,Time Factors ,Treatment Outcome ,United States ,Viral Load ,Viral load ,medicine.medical_specialty ,MESH: Interleukins ,Interferon alpha-2 ,MESH: Phenotype ,03 medical and health sciences ,Drug Therapy ,MESH: Ribavirin ,MESH: Canada ,Boceprevir ,Polymorphism ,MESH: Proline ,MESH: Humans ,MESH: Adult ,Odds ratio ,medicine.disease ,digestive system diseases ,Clinical trial ,chemistry ,Immunology ,MESH: Female ,medicine.disease_cause ,chemistry.chemical_compound ,Interferon ,MESH: Risk Factors ,MESH: Hepacivirus ,Viral ,Single Nucleotide ,Combination ,MESH: Interferon-alpha ,MESH: Viral Load ,medicine.drug ,MESH: Antiviral Agents ,Hepatitis C virus ,MESH: Multivariate Analysis ,Internal medicine ,medicine ,MESH: United States ,030304 developmental biology ,MESH: Hepatitis C ,Hepatology ,business.industry ,MESH: Time Factors ,MESH: Biological Markers ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,MESH: Prospective Studies ,MESH: Male ,MESH: Odds Ratio ,MESH: Drug Therapy, Combination ,MESH: Polyethylene Glycols ,RNA ,Interferons ,MESH: Europe ,business - Abstract
Background & Aims Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors. Methods Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28–48 wk). A good response to interferon was defined as a ≥1 log 10 decrease in HCV RNA at week 4; a poor response was defined as a 10 decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism interleukin [ IL ]- 28B rs12979860) associated with response. The polymorphism IL - 28B rs8099917 also was assessed. Results In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous nonresponse (OR, 2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%–89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was associated more strongly with a good response to interferon than other baseline factors; however, a ≥1 log 10 decrease in HCV-RNA level at week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR. Conclusions The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥1 log 10 decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B . ClinicalTrials.gov; numbers NCT00705432 and NCT00708500.
- Published
- 2012
4. Pneumococcal Conjugate Vaccine Impact on Serotype 3: A Review of Surveillance Data.
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Sings HL, Gessner BD, Wasserman MD, and Jodar L
- Abstract
Introduction: Limited changes in serotype 3 invasive pneumococcal disease (IPD) incidence rates after a decade of 13-valent pneumococcal conjugate vaccine (PCV13) introduction into several national immunization programs (NIP) have raised questions about PCV13's effectiveness against this serotype., Methods: We analyzed the impact of pediatric PCV programs on serotype 3 IPD with two approaches. First, we reviewed the publicly available surveillance data from countries identified in two recently published reviews to describe the population impact of pediatric PCV13 or PCV10 vaccination programs on serotype 3 IPD. We then compared the observed trends in PCV10 and PCV13 countries to a previously described dynamic transmission model that simulates the spread of pneumococcal carriage and development of IPD in a population over time., Results: When serotype 3 disease rates are compared from countries that have introduced either a 10-valent (PCV10) vaccine that does not contain serotype 3 in its formulation or PCV13 in their pediatric NIP, over time, serotype 3 incidence rate trends are markedly different. Countries with a PCV10 NIP showed a substantial linear increase in serotype 3 pneumococcal disease among all age groups since the time of PCV10 introduction, whereas countries with a PCV13 NIP experienced a modest decline during the 3-4 years after vaccine introduction followed by an inflection upward in subsequent years., Conclusion: These data suggest that PCV13 provides a certain degree of direct and indirect protection against serotype 3 at the population level and direct adult vaccination with a serotype 3-containing vaccine is likely to provide substantial benefit in the context of a pediatric PCV NIP. Further research around serotype 3 transmission patterns and epidemiology is nonetheless warranted.
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- 2021
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5. Health and Economic Impact of Routine Pediatric Pneumococcal Immunization Programs in Canada: A Retrospective Analysis.
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Wilson MR, Wasserman MD, Breton MC, Peloquin F, Earnshaw SR, McDade C, Sings HL, and Farkouh RA
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Objective: A model was developed to estimate the historical impact (including total societal health and economic benefit) of pneumococcal conjugate vaccine (PCV) programs in the overall Canadian population between 2005 and 2015, inclusively., Methods: Historical incidence of invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) were obtained from epidemiologic databases supplemented with published and unpublished data. Two scenarios were considered: (1) the observed historical incidence from 2005 to 2015 in the setting of PCV use; (2) a hypothetical scenario in which we estimated the number of disease cases assuming no PCV use. Disease cases averted as a result of PCV programs were calculated by subtracting the number of observed historical cases from the number of estimated cases expected in the absence of PCV use., Results: PCV programs were estimated to have saved 6631 lives and averted 14,990 IPD cases, 735,700 pneumonia episodes, and 3,697,993 AOM episodes. Positive clinical outcomes resulted in total cost savings of CAD $1.76 billion over 11 years. Vaccination costs were offset by the direct medical cost savings from fewer cases of IPD, pneumonia, and AOM., Conclusions: Canadian PCV programs have provided significant health benefits and resulted in a substantial value for money. Net savings achieved over the reviewed period would have provided funding for $1.76 billion in other health care costs or public health initiatives. These findings highlight the importance of considering the total value of a vaccination program, rather than vaccine acquisition costs only, when assessing the value of immunization programs.
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- 2020
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6. Re-Analysis of Modeling a Switch from a 13-Valent to 10-Valent Pneumococcal Conjugate Vaccine in Canada: Leveraging Real-World Experience from Belgium.
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Wasserman MD, Sings HL, Wilson MR, Postma MJ, Breton MC, McDade C, and Farkouh RA
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- 2019
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7. Response to McGirr et al.'s Comment on "Clinical and Economic Impact of a Potential Switch from 13-Valent to 10-Valent Pneumococcal Conjugate Infant Vaccination in Canada".
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Wilson MR, Wasserman M, Jadavji T, Postma M, Breton MC, Peloquin F, Earnshaw SR, McDade C, Sings HL, and Farkouh R
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- 2018
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8. Response to Effectiveness of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D-Conjugated Vaccine (PHiD-CV) Against Carriage and Acute Otitis Media-A Double-Blind Randomized Clinical Trial in Finland.
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Sings HL and Isturiz R
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- Double-Blind Method, Finland, Haemophilus influenzae, Humans, Vaccines, Conjugate, Otitis Media, Pneumococcal Vaccines
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- 2017
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9. Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region.
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Castellsagué X, Ault KA, Bosch FX, Brown D, Cuzick J, Ferris DG, Joura EA, Garland SM, Giuliano AR, Hernandez-Avila M, Huh W, Iversen OE, Kjaer SK, Luna J, Monsonego J, Muñoz N, Myers E, Paavonen J, Pitisuttihum P, Steben M, Wheeler CM, Perez G, Saah A, Luxembourg A, Sings HL, and Velicer C
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- Adolescent, Adult, Asia, Europe, Female, Humans, Latin America, Middle Aged, North America, Papillomaviridae genetics, Randomized Controlled Trials as Topic, Young Adult, Adenocarcinoma virology, Genotype, Papillomaviridae classification, Papillomaviridae isolation & purification, Uterine Cervical Dysplasia virology
- Abstract
Background: We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region METHODS: Women ages 15-26 and 24-45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus., Results: Predominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (~50%) and CIN2/3 (81-85%). Types 31/33/45/52/58 accounted for 25-30% of CIN1 in Latin America and Europe, but 14-18% in North America and Asia. Types 31/33/45/52/58 accounted for 33-38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17-18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2-11% of CIN2/3., Conclusions: The 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2016
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10. Attribution of 12 high-risk human papillomavirus genotypes to infection and cervical disease.
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Joura EA, Ault KA, Bosch FX, Brown D, Cuzick J, Ferris D, Garland SM, Giuliano AR, Hernandez-Avila M, Huh W, Iversen OE, Kjaer SK, Luna J, Miller D, Monsonego J, Munoz N, Myers E, Paavonen J, Pitisuttithum P, Steben M, Wheeler CM, Perez G, Saah A, Luxembourg A, Sings HL, and Velicer C
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- Adolescent, Adult, Double-Blind Method, Female, Genotype, Humans, Incidence, Middle Aged, Papillomavirus Infections epidemiology, Papillomavirus Infections genetics, Papillomavirus Vaccines therapeutic use, Prevalence, Risk Factors, Uterine Cervical Neoplasms prevention & control, Young Adult, Uterine Cervical Dysplasia prevention & control, Papillomaviridae genetics, Papillomavirus Infections virology, Uterine Cervical Neoplasms virology, Uterine Cervical Dysplasia virology
- Abstract
Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined algorithms that adjusted for multiple-type infected lesions., Methods: A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine., Results: The cumulative incidence of persistent infection with ≥1 of the seven high-risk types included in the 9-valent vaccine was 29%, 12%, and 6% for women ages 15 to 26, 24 to 34, and 35 to 45 years, respectively. A total of 2,507 lesions were diagnosed as CIN or AIS by an expert pathology panel. After adjusting for multiple-type infected lesions, among women ages 15 to 45 years, these seven high-risk types were attributed to 43% to 55% of CIN1, 70% to 78% of CIN2, 85% to 91% of CIN3, and 95% to 100% of AIS lesions, respectively. The other tested types (HPV35/39/51/56/59) were attributed to 23% to 30% of CIN1, 7% to 14% of CIN2, 3% to 4% of CIN3, and 0% of AIS lesions, respectively., Conclusions: Approximately 85% or more of CIN3/AIS, >70% CIN2, and approximately 50% of CIN1 lesions worldwide are attributed to HPV6/11/16/18/31/33/45/52/58., Impact: If 9-valent HPV vaccination programs are effectively implemented, the majority of CIN2 and CIN3 lesions worldwide could be prevented, in addition to approximately one-half of CIN1., (©2014 American Association for Cancer Research.)
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- 2014
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11. Boceprevir with peginterferon alfa-2a-ribavirin is effective for previously treated chronic hepatitis C genotype 1 infection.
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Flamm SL, Lawitz E, Jacobson I, Bourlière M, Hezode C, Vierling JM, Bacon BR, Niederau C, Sherman M, Goteti V, Sings HL, Barnard RO, Howe JA, Pedicone LD, Burroughs MH, Brass CA, Albrecht JK, and Poordad F
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- Adult, Aged, Double-Blind Method, Female, Genotype, Hepacivirus classification, Hepacivirus genetics, Hepatitis C, Chronic virology, Humans, Male, Middle Aged, Placebos administration & dosage, Proline administration & dosage, RNA, Viral blood, Recombinant Proteins administration & dosage, Treatment Outcome, Viral Load, Antiviral Agents administration & dosage, Hepatitis C, Chronic drug therapy, Interferon-alpha administration & dosage, Polyethylene Glycols administration & dosage, Proline analogs & derivatives, Ribavirin administration & dosage
- Abstract
Background & Aims: The addition of boceprevir to therapy with peginterferon alfa-2b and ribavirin results in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection, compared with peginterferon alfa-2b and ribavirin alone. We assessed SVR with boceprevir plus peginterferon alfa-2a-ribavirin (PEG2a/R) in patients with identical study entry criteria., Methods: In a double-blind, placebo-controlled trial, 201 patients with HCV genotype-1 who had relapsed or not responded to previous therapy were assigned to groups (1:2) and given a 4-week lead-in phase of PEG2a/R, followed by placebo plus PEG2a/R for 44 weeks (PEG2a/R) or boceprevir plus PEG2a/R for 44 weeks (BOC/PEG2a/R). The primary end point was SVR 24 weeks after therapy ended., Results: The addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R significantly increased the rate of SVR from 21% in the PEG2a/R group to 64% in the BOC/PEG2a/R group (P < .0001). Among patients with poor response to interferon therapy (<1-log(10) decline in HCV RNA at week 4), 39% in the BOC/PEG2a/R group had SVRs, compared with none of the patients in the PEG2a/R group. Among patients with good response to interferon (≥1-log(10) decline), 71% in the BOC/PEG2a/R group had SVRs, compared with 25% in the PEG2a/R group. A ≥1-log(10) decline in HCV RNA at treatment week 4 was the strongest independent predictor of SVR, exceeding that of IL-28B genotype. Among 8 patients who began the study with HCV amino acid variants associated with boceprevir resistance, 3 (38%) achieved SVRs. Fifty percent of patients in the BOC/PEG2a/R group developed anemia (hemoglobin <10.0 g/dL), compared with 27% in the PEG2a/R group; 43% vs 21%, respectively, developed neutropenia (neutrophil count <750/mm(3))., Conclusions: The addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R caused significantly higher rates of SVR in previously treated patients with chronic HCV genotype-1 infection, compared with patients given only PEG2a/R. ClinicalTrials.gov Identifier: NCT00845065., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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12. Factors that predict response of patients with hepatitis C virus infection to boceprevir.
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Poordad F, Bronowicki JP, Gordon SC, Zeuzem S, Jacobson IM, Sulkowski MS, Poynard T, Morgan TR, Molony C, Pedicone LD, Sings HL, Burroughs MH, Sniukiene V, Boparai N, Goteti VS, Brass CA, Albrecht JK, and Bacon BR
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- Adult, Biomarkers blood, Canada, Drug Therapy, Combination, Europe, Female, Genotype, Hepacivirus genetics, Hepacivirus growth & development, Hepatitis C diagnosis, Hepatitis C genetics, Humans, Interferon alpha-2, Interferon-alpha therapeutic use, Interferons, Interleukins genetics, Logistic Models, Male, Multivariate Analysis, Odds Ratio, Phenotype, Polyethylene Glycols therapeutic use, Polymorphism, Single Nucleotide, Proline therapeutic use, Prospective Studies, RNA, Viral blood, Recombinant Proteins therapeutic use, Ribavirin therapeutic use, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, United States, Viral Load, Antiviral Agents therapeutic use, Hepacivirus drug effects, Hepatitis C drug therapy, Proline analogs & derivatives
- Abstract
Background & Aims: Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors., Methods: Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28-48 wk). A good response to interferon was defined as a ≥ 1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a <1 log(10) decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism interleukin [IL]-28B rs12979860) associated with response. The polymorphism IL-28B rs8099917 also was assessed., Results: In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous nonresponse (OR, 2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%-89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was associated more strongly with a good response to interferon than other baseline factors; however, a ≥ 1 log(10) decrease in HCV-RNA level at week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR., Conclusions: The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥ 1 log(10) decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)
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- 2012
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13. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data.
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Joura EA, Garland SM, Paavonen J, Ferris DG, Perez G, Ault KA, Huh WK, Sings HL, James MK, and Haupt RM
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- Adolescent, Double-Blind Method, Female, Humans, Incidence, Papillomavirus Infections epidemiology, Retrospective Studies, United States epidemiology, Uterine Cervical Neoplasms epidemiology, Victoria epidemiology, Vulvar Neoplasms epidemiology, Young Adult, Papillomaviridae immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms prevention & control, Vaccination methods, Vulvar Neoplasms prevention & control
- Abstract
Objectives: To determine the effect of human papillomavirus (HPV) quadrivalent vaccine on the risk of developing subsequent disease after an excisional procedure for cervical intraepithelial neoplasia or diagnosis of genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia., Design: Retrospective analysis of data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II))., Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world., Participants: Among 17,622 women aged 15-26 years who underwent 1:1 randomisation to vaccine or placebo, 2054 received cervical surgery or were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia., Intervention: Three doses of quadrivalent HPV vaccine or placebo at day 1, month 2, and month 6., Main Outcome Measures: Incidence of HPV related disease from 60 days after treatment or diagnosis, expressed as the number of women with an end point per 100 person years at risk., Results: A total of 587 vaccine and 763 placebo recipients underwent cervical surgery. The incidence of any subsequent HPV related disease was 6.6 and 12.2 in vaccine and placebo recipients respectively (46.2% reduction (95% confidence interval 22.5% to 63.2%) with vaccination). Vaccination was associated with a significant reduction in risk of any subsequent high grade disease of the cervix by 64.9% (20.1% to 86.3%). A total of 229 vaccine recipients and 475 placebo recipients were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia, and the incidence of any subsequent HPV related disease was 20.1 and 31.0 in vaccine and placebo recipients respectively (35.2% reduction (13.8% to 51.8%))., Conclusions: Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease, including high grade disease., Trial Registrations: NCT00092521 and NCT00092534.
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- 2012
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14. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.
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Muñoz N, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia PJ, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Huh WK, Joura EA, Kurman RJ, Majewski S, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan JT, Lupinacci LC, Giacoletti KE, Sings HL, James MK, Hesley TM, Barr E, and Haupt RM
- Subjects
- Adolescent, Adult, Female, Genital Diseases, Female prevention & control, Genital Diseases, Female virology, Global Health, Human papillomavirus 11 immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Humans, Kaplan-Meier Estimate, Papanicolaou Test, Papillomavirus Infections complications, Papillomavirus Infections epidemiology, Papillomavirus Infections virology, Sexual Partners, Sexually Transmitted Diseases epidemiology, Sexually Transmitted Diseases virology, Tumor Virus Infections complications, Tumor Virus Infections epidemiology, Tumor Virus Infections virology, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Neoplasms virology, Vaginal Smears, Young Adult, Uterine Cervical Dysplasia epidemiology, Uterine Cervical Dysplasia virology, Alphapapillomavirus immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines pharmacology, Sexually Transmitted Diseases prevention & control, Tumor Virus Infections prevention & control, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Dysplasia prevention & control
- Abstract
Background: The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group)., Methods: This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk., Results: The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type., Conclusions: High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.
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- 2010
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15. Human papillomavirus infections and vulvar disease development.
- Author
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Garland SM, Insinga RP, Sings HL, Haupt RM, and Joura EA
- Subjects
- Adolescent, Adult, Cancer Vaccines therapeutic use, DNA, Viral analysis, DNA, Viral isolation & purification, Double-Blind Method, Female, Humans, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Polymerase Chain Reaction, Precancerous Conditions virology, Vulvar Neoplasms prevention & control, Carcinoma in Situ virology, Human papillomavirus 11, Human papillomavirus 16, Papillomavirus Infections complications, Vulvar Neoplasms virology
- Abstract
Background: We describe the prevalence of 14 common types [human papillomavirus (HPV)-6/11/16/18/31/33/35/39/45/51/52/56/58/59] in vulvar intraepithelial neoplasia grades 1 to 3 (VIN 1-3) and HPV genotype-specific infection in relation to the development of VIN 1-3., Methods: Data were analyzed from women enrolled in the placebo arms of three randomized double-blind trials. Anogenital examinations, including collection of labial/vulvar/perineal/perianal swabs, occurred at day 1 and every 6 to 12 months through 48 months. Lesions that were possibly, probably, or definitely HPV related or of unknown etiology were biopsied. Biopsies and swabs were HPV typed. Biopsies were read for endpoint determination (VIN 1-3) by up to four pathologists., Results: Incident infection with HPV-16 was the most common (6.0/100 person-years). The mean time from incident infection to the development of VIN 1-3 was 18.5 months (95% confidence interval, 13.4-23.6). HPV-6 or -11 was observed in 64.5% of VIN 1 and 29.0% of VIN 2/3, whereas HPV-16 was observed in 6.5% of VIN 1 and 64.5% of VIN 2/3., Conclusion: A vaccine that includes both low- and high-risk types could prevent more than half of VIN 1-3 lesions, including the precursor lesions to HPV-related vulvar carcinoma. Understanding the incidence and duration of vulvar HPV infection and risk for progression to VIN 1-3 may inform therapeutic decisions for vulvar disease and mathematical models that assess the cost-effectiveness of vaccination.
- Published
- 2009
- Full Text
- View/download PDF
16. Incidence and risk factors for genital Chlamydia trachomatis infection: a 4-year prospective cohort study.
- Author
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Skjeldestad FE, Marsico MA, Sings HL, Nordbø SA, and Størvold G
- Subjects
- Adolescent, Adult, Age Factors, Chlamydia Infections prevention & control, Female, Humans, Incidence, Logistic Models, Norway epidemiology, Prospective Studies, Risk Factors, Sexual Behavior, Sexual Partners, Chlamydia Infections epidemiology, Chlamydia trachomatis
- Abstract
Background: Few long-term studies reporting incidence and behavioral data for Chlamydia trachomatis (CT) infection in the general population have been published. Such studies are important to understand risk factors associated with infection and to develop screening recommendations., Methods: A fixed prospective 4-year cohort study of 898 sexually active Norwegian women, aged 16 to 23 years at study start, was conducted to assess incidence, repeat infection, and risk factors associated with genital CT infection. Participants were interviewed at study start and at 6-month intervals thereafter for behavioral characteristics. The women were tested for CT infection at 12-month intervals beginning at study start. Risk factors were assessed using Fisher exact test and conditional logistic regression. Person-time was estimated in survival analyses and incidence of CT infection was reported as events per 100 woman-years., Results: Median duration of observation was 48.0 months (range 10-74) whereas 4.4 specimens were collected per woman (range 2-5). Of the 836 women eligible for the analysis, 19 (2.2%) had a prevalent infection at baseline. The 4-year cumulative incidence of CT infection was 7.7 (95% CI: 6.7-8.7) with annual incidences ranging from 1.2 to 2.9 per 100 woman-years. The 2-year cumulative incidence of repeat CT infection was 11.2 (95% CI: 9.3-13.1) per 100 woman-years. In multivariate analyses, factors associated with incident CT infection were young age (< or =24 years) and number of new partners over the last 12 months prior being tested., Conclusion: The annual incidences observed for women 24 years or younger with 1 or more new partners over the last 12 months support recommendations for annual testing for CT in this age group in Norway.
- Published
- 2009
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17. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years.
- Author
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Brown DR, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Joura EA, Kurman RJ, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Sings HL, James M, Hesley TM, and Barr E
- Subjects
- Adolescent, Adult, Alphapapillomavirus classification, Alphapapillomavirus genetics, Female, Humans, Papillomavirus Infections virology, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Neoplasms virology, Young Adult, Alphapapillomavirus immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines
- Abstract
Background: Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated., Methods: We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types., Results: Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31., Conclusions: HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for approximately 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type., Trial Registration: ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
- Published
- 2009
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18. Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine.
- Author
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Garland SM, Steben M, Sings HL, James M, Lu S, Railkar R, Barr E, Haupt RM, and Joura EA
- Subjects
- Adolescent, Adult, Clinical Trials, Phase III as Topic, Condylomata Acuminata epidemiology, Female, Follow-Up Studies, Genotype, Human papillomavirus 16 genetics, Human papillomavirus 18 genetics, Human papillomavirus 6 genetics, Humans, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Randomized Controlled Trials as Topic, Risk Factors, Time Factors, Young Adult, Condylomata Acuminata immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Papillomavirus Infections immunology, Viral Vaccines administration & dosage
- Abstract
Background: The placebo arm of human papillomavirus (HPV) vaccine trials helps define the natural history of genital warts (GW)., Methods: Women enrolled in the placebo arm (n = 8800) of 2 randomized trials of a quadrivalent vaccine were examined for the presence of GW for up to 9 visits over approximately 4 years. A comprehensive examination of the perianal area, vulva, and vagina prompted biopsy. Biopsy samples were analyzed by a blinded panel of up to 4 histopathologists and tested for 14 HPV genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) by use of a polymerase chain reaction-based assay. Risk factors for the development of GW were assessed., Results: Women were followed up for an average of 3.6 years (range, 0-4.9 years). Overall, 298 (3.4%) of 8800 participants developed GW related to HPV-6 or HPV-11 (incidence rate, 0.87 cases per 100 person-years-at-risk). In total, 520 distinct lesions were diagnosed as GW. HPV DNA was detected in 472 (90.8%) lesions, with HPV-6 and HPV-11 detected in 447 (86.0%) of these lesions (94.7% of 472 HPV DNA-positive lesions). We found high-risk HPV types in 161 (31.0%) of 520 lesions. Risk factors for HPV-6- and HPV-11-related GW included infection at baseline, acquisition of new sex partners, a higher number of sex partners, and DNA positivity at baseline for a high-risk HPV type., Conclusions: We confirm the major role played by HPV-6 and HPV-11 in GW, as well as associated risk factors. A vaccine that includes these types of HPV could substantially reduce the overall burden of HPV disease.
- Published
- 2009
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19. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.
- Author
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Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, Olsson SE, Høye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, Krogh Gv, Lehtinen M, Malm C, Tamms GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo FJ, Bryan J, Esser MT, Sings HL, Saah AJ, and Barr E
- Subjects
- Adolescent, Adult, Alphapapillomavirus immunology, Antibodies, Viral blood, Condylomata Acuminata prevention & control, Double-Blind Method, Female, Follow-Up Studies, Humans, Incidence, Papillomavirus Infections epidemiology, Uterine Cervical Dysplasia prevention & control, Vaginal Smears, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms prevention & control, Virion immunology
- Abstract
Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.
- Published
- 2006
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20. Acyl tunichlorins: a new class of nickel chlorins isolated from the Caribbean tunicate Trididemnum solidum.
- Author
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Sings HL, Bible KC, and Rinehart KL
- Subjects
- Animals, Disulfides chemistry, Esters, Gas Chromatography-Mass Spectrometry, Magnetic Resonance Spectroscopy, Nickel, Pigments, Biological chemistry, Metalloporphyrins chemistry, Urochordata chemistry
- Abstract
A new class of nickel-containing chlorins (acyl tunichlorins) has been isolated from the Caribbean tunicate Trididemnum solidum. The structures of 28 of these nickel (II) hydroporphyrins were elucidated using mass spectrometry, one- and two-dimensional NMR spectroscopy, and chemical degradation/derivatization. Unique structural features of these compounds include the diversity of aliphatic side chains, which are derived from C14:0 to C22:6 fatty acids, and their location at an unprecedented position at C-2a on the hydroporphyrin nucleus. No chlorins with ester-linked acyl side chains at C-2a have been reported previously. Although the exact biological role that these compounds play in T. solidum remains unknown, acyl tunichlorins represent the only nickel-containing chlorins to be isolated from a living system and are the C-2a acyl derivatives of tunichlorin, a nickel chlorin reported by this laboratory in 1988.
- Published
- 1996
- Full Text
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