Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study

Detalhes bibliográficos
Autor(a) principal: Ribeiro,Karina Mota
Data de Publicação: 2014
Outros Autores: Biscione,Fernando Martin, Westin,Mateus Rodrigues, Machado,Danielle Pessoa, Greco,Dirceu Bartolomeu, Tupinambás,Unaí
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Infectious Diseases
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702014000100001
Resumo: Background:Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil.Methods:Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load <50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression.Results:Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI = 69.7–86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI = 103.4–159.6). In multiple logistic regression analysis, higher baseline viral load (RR = 1.04 per 10,000 copies/mL increase; 95% CI = 1.01–1.09) and higher number of darunavir resistance-associated mutations (RR = 1.23 per each; 95% CI = 0.95–1.48) were independently associated with virologic failure.Conclusion:Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings.
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spelling Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort studyHIV-1Highly active antiretroviral therapySalvage therapyMultiple viral drug resistanceGenotyping techniquesBackground:Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil.Methods:Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load <50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression.Results:Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI = 69.7–86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI = 103.4–159.6). In multiple logistic regression analysis, higher baseline viral load (RR = 1.04 per 10,000 copies/mL increase; 95% CI = 1.01–1.09) and higher number of darunavir resistance-associated mutations (RR = 1.23 per each; 95% CI = 0.95–1.48) were independently associated with virologic failure.Conclusion:Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings.Brazilian Society of Infectious Diseases2014-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702014000100001Brazilian Journal of Infectious Diseases v.18 n.1 2014reponame:Brazilian Journal of Infectious Diseasesinstname:Brazilian Society of Infectious Diseases (BSID)instacron:BSID10.1016/j.bjid.2013.04.001info:eu-repo/semantics/openAccessRibeiro,Karina MotaBiscione,Fernando MartinWestin,Mateus RodriguesMachado,Danielle PessoaGreco,Dirceu BartolomeuTupinambás,Unaíeng2015-08-28T00:00:00Zoai:scielo:S1413-86702014000100001Revistahttps://www.bjid.org.br/https://old.scielo.br/oai/scielo-oai.phpbjid@bjid.org.br||lgoldani@ufrgs.br1678-43911413-8670opendoar:2015-08-28T00:00Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID)false
dc.title.none.fl_str_mv Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
title Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
spellingShingle Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
Ribeiro,Karina Mota
HIV-1
Highly active antiretroviral therapy
Salvage therapy
Multiple viral drug resistance
Genotyping techniques
title_short Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
title_full Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
title_fullStr Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
title_full_unstemmed Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
title_sort Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study
author Ribeiro,Karina Mota
author_facet Ribeiro,Karina Mota
Biscione,Fernando Martin
Westin,Mateus Rodrigues
Machado,Danielle Pessoa
Greco,Dirceu Bartolomeu
Tupinambás,Unaí
author_role author
author2 Biscione,Fernando Martin
Westin,Mateus Rodrigues
Machado,Danielle Pessoa
Greco,Dirceu Bartolomeu
Tupinambás,Unaí
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Ribeiro,Karina Mota
Biscione,Fernando Martin
Westin,Mateus Rodrigues
Machado,Danielle Pessoa
Greco,Dirceu Bartolomeu
Tupinambás,Unaí
dc.subject.por.fl_str_mv HIV-1
Highly active antiretroviral therapy
Salvage therapy
Multiple viral drug resistance
Genotyping techniques
topic HIV-1
Highly active antiretroviral therapy
Salvage therapy
Multiple viral drug resistance
Genotyping techniques
description Background:Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil.Methods:Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load <50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression.Results:Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI = 69.7–86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI = 103.4–159.6). In multiple logistic regression analysis, higher baseline viral load (RR = 1.04 per 10,000 copies/mL increase; 95% CI = 1.01–1.09) and higher number of darunavir resistance-associated mutations (RR = 1.23 per each; 95% CI = 0.95–1.48) were independently associated with virologic failure.Conclusion:Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings.
publishDate 2014
dc.date.none.fl_str_mv 2014-01-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702014000100001
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702014000100001
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1016/j.bjid.2013.04.001
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Brazilian Society of Infectious Diseases
publisher.none.fl_str_mv Brazilian Society of Infectious Diseases
dc.source.none.fl_str_mv Brazilian Journal of Infectious Diseases v.18 n.1 2014
reponame:Brazilian Journal of Infectious Diseases
instname:Brazilian Society of Infectious Diseases (BSID)
instacron:BSID
instname_str Brazilian Society of Infectious Diseases (BSID)
instacron_str BSID
institution BSID
reponame_str Brazilian Journal of Infectious Diseases
collection Brazilian Journal of Infectious Diseases
repository.name.fl_str_mv Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID)
repository.mail.fl_str_mv bjid@bjid.org.br||lgoldani@ufrgs.br
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