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
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , |
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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Brazilian Journal of Infectious Diseases |
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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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1754209242801242112 |