A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease

Background: Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability. Methods: We evaluated the antiviral activity...

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Autores: Danner, Sven A., Carr, Andrew, Leonard, John M., Lehman, Leah M., Gudiol i Munté, Francesc, Gonzales, Juan, Raventós, Antonio, Rubio, Rafael, Bouza, Emilio, Pintado, Vicente, Gil Aguado, Antonio, Garcia de Lomas, Juan, Delgado, Rafael, Borleffs, Jan C.C., Hsu, Ann, Valdes, Joaquin M., Boucher, Charles A. B., Cooper, David A., European-Australian Collaborative Ritonavir Study Group
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1995
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/121979
Acceso en línea:https://hdl.handle.net/2445/121979
Access Level:acceso abierto
Palabra clave:Infeccions per VIH
Antiretrovirals
Estudi de casos
HIV infections
Antiretroviral agents
Case studies
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spelling A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 proteaseDanner, Sven A.Carr, AndrewLeonard, John M.Lehman, Leah M.Gudiol i Munté, FrancescGonzales, JuanRaventós, AntonioRubio, RafaelBouza, EmilioPintado, VicenteGil Aguado, AntonioGarcia de Lomas, JuanDelgado, RafaelBorleffs, Jan C.C.Hsu, AnnValdes, Joaquin M.Boucher, Charles A. B.Cooper, David A.European-Australian Collaborative Ritonavir Study GroupInfeccions per VIHAntiretroviralsEstudi de casosHIV infectionsAntiretroviral agentsCase studiesBackground: Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability. Methods: We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4+ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens. Results: During the first 4 weeks, increases in CD4+ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lower-dosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavir every 12 hours), the median increase from base line in the CD4+ lymphocyte count was 230 cells per cubic millimeter, and the mean decrease in the plasma concentration of HIV-1 RNA (as measured by a branched-chain DNA assay) was 0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup of 17 patients in the two higher-dosage groups, RNA was also measured with an assay based on the polymerase chain reaction, and after eight weeks of treatment there was a mean maximal decrease in viral RNA of 1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events included nausea, circumoral paresthesia, elevated hepatic aminotransferase levels, and elevated triglyceride levels. Ten withdrawals from the study were judged to be related to ritonavir treatment. Conclusions: In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.Massachusetts Medical Society1995info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/121979Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1056/NEJM199512073332303New England Journal of Medicine, 1995, vol. 333, num. 23, p. 1528-1533https://doi.org/10.1056/NEJM199512073332303(c) Massachusetts Medical Society, 1995info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1219792026-05-27T06:46:51Z
dc.title.none.fl_str_mv A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
title A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
spellingShingle A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
Danner, Sven A.
Infeccions per VIH
Antiretrovirals
Estudi de casos
HIV infections
Antiretroviral agents
Case studies
title_short A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
title_full A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
title_fullStr A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
title_full_unstemmed A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
title_sort A short-term study of the safety pharmacokinetics and efficacy of ritonavir, an inhibitor of HIV-1 protease
dc.creator.none.fl_str_mv Danner, Sven A.
Carr, Andrew
Leonard, John M.
Lehman, Leah M.
Gudiol i Munté, Francesc
Gonzales, Juan
Raventós, Antonio
Rubio, Rafael
Bouza, Emilio
Pintado, Vicente
Gil Aguado, Antonio
Garcia de Lomas, Juan
Delgado, Rafael
Borleffs, Jan C.C.
Hsu, Ann
Valdes, Joaquin M.
Boucher, Charles A. B.
Cooper, David A.
European-Australian Collaborative Ritonavir Study Group
author Danner, Sven A.
author_facet Danner, Sven A.
Carr, Andrew
Leonard, John M.
Lehman, Leah M.
Gudiol i Munté, Francesc
Gonzales, Juan
Raventós, Antonio
Rubio, Rafael
Bouza, Emilio
Pintado, Vicente
Gil Aguado, Antonio
Garcia de Lomas, Juan
Delgado, Rafael
Borleffs, Jan C.C.
Hsu, Ann
Valdes, Joaquin M.
Boucher, Charles A. B.
Cooper, David A.
European-Australian Collaborative Ritonavir Study Group
author_role author
author2 Carr, Andrew
Leonard, John M.
Lehman, Leah M.
Gudiol i Munté, Francesc
Gonzales, Juan
Raventós, Antonio
Rubio, Rafael
Bouza, Emilio
Pintado, Vicente
Gil Aguado, Antonio
Garcia de Lomas, Juan
Delgado, Rafael
Borleffs, Jan C.C.
Hsu, Ann
Valdes, Joaquin M.
Boucher, Charles A. B.
Cooper, David A.
European-Australian Collaborative Ritonavir Study Group
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Infeccions per VIH
Antiretrovirals
Estudi de casos
HIV infections
Antiretroviral agents
Case studies
topic Infeccions per VIH
Antiretrovirals
Estudi de casos
HIV infections
Antiretroviral agents
Case studies
description Background: Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability. Methods: We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4+ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens. Results: During the first 4 weeks, increases in CD4+ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lower-dosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavir every 12 hours), the median increase from base line in the CD4+ lymphocyte count was 230 cells per cubic millimeter, and the mean decrease in the plasma concentration of HIV-1 RNA (as measured by a branched-chain DNA assay) was 0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup of 17 patients in the two higher-dosage groups, RNA was also measured with an assay based on the polymerase chain reaction, and after eight weeks of treatment there was a mean maximal decrease in viral RNA of 1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events included nausea, circumoral paresthesia, elevated hepatic aminotransferase levels, and elevated triglyceride levels. Ten withdrawals from the study were judged to be related to ritonavir treatment. Conclusions: In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.
publishDate 1995
dc.date.none.fl_str_mv 1995
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/121979
url https://hdl.handle.net/2445/121979
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1056/NEJM199512073332303
New England Journal of Medicine, 1995, vol. 333, num. 23, p. 1528-1533
https://doi.org/10.1056/NEJM199512073332303
dc.rights.none.fl_str_mv (c) Massachusetts Medical Society, 1995
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Massachusetts Medical Society, 1995
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Massachusetts Medical Society
publisher.none.fl_str_mv Massachusetts Medical Society
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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