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Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

BACKGROUND: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. METHODS: In this prospective cohort we enrolled patients...

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Autores principales: Maggiolo, Franco, Gulminetti, Roberto, Pagnucco, Layla, Digaetano, Margherita, Benatti, Simone, Valenti, Daniela, Callegaro, Annapaola, Ripamonti, Diego, Mussini, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356275/
https://www.ncbi.nlm.nih.gov/pubmed/28302065
http://dx.doi.org/10.1186/s12879-017-2311-2
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author Maggiolo, Franco
Gulminetti, Roberto
Pagnucco, Layla
Digaetano, Margherita
Benatti, Simone
Valenti, Daniela
Callegaro, Annapaola
Ripamonti, Diego
Mussini, Cristina
author_facet Maggiolo, Franco
Gulminetti, Roberto
Pagnucco, Layla
Digaetano, Margherita
Benatti, Simone
Valenti, Daniela
Callegaro, Annapaola
Ripamonti, Diego
Mussini, Cristina
author_sort Maggiolo, Franco
collection PubMed
description BACKGROUND: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. METHODS: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART. RESULTS: Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10). DISCUSSION: Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms. CONCLUSION: Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2311-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-53562752017-03-22 Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients Maggiolo, Franco Gulminetti, Roberto Pagnucco, Layla Digaetano, Margherita Benatti, Simone Valenti, Daniela Callegaro, Annapaola Ripamonti, Diego Mussini, Cristina BMC Infect Dis Research Article BACKGROUND: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. METHODS: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART. RESULTS: Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10). DISCUSSION: Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms. CONCLUSION: Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2311-2) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-16 /pmc/articles/PMC5356275/ /pubmed/28302065 http://dx.doi.org/10.1186/s12879-017-2311-2 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Maggiolo, Franco
Gulminetti, Roberto
Pagnucco, Layla
Digaetano, Margherita
Benatti, Simone
Valenti, Daniela
Callegaro, Annapaola
Ripamonti, Diego
Mussini, Cristina
Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients
title Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients
title_full Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients
title_fullStr Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients
title_full_unstemmed Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients
title_short Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients
title_sort lamivudine/dolutegravir dual therapy in hiv-infected, virologically suppressed patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356275/
https://www.ncbi.nlm.nih.gov/pubmed/28302065
http://dx.doi.org/10.1186/s12879-017-2311-2
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