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1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable

BACKGROUND: A drug-drug interaction study between dolutegravir and doravirine in healthy volunteers found no evidence of untoward interaction. Whilst we hypothesize that the combination would be safe and effective, there is no supportive clinical data. We aimed to assess the rationale for use of dol...

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Autores principales: Denyer, Rachel, Zemskova, Julie, Beatty, Daniel, Benator, Debra A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7777508/
http://dx.doi.org/10.1093/ofid/ofaa439.1195
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author Denyer, Rachel
Zemskova, Julie
Beatty, Daniel
Benator, Debra A
author_facet Denyer, Rachel
Zemskova, Julie
Beatty, Daniel
Benator, Debra A
author_sort Denyer, Rachel
collection PubMed
description BACKGROUND: A drug-drug interaction study between dolutegravir and doravirine in healthy volunteers found no evidence of untoward interaction. Whilst we hypothesize that the combination would be safe and effective, there is no supportive clinical data. We aimed to assess the rationale for use of dolutegravir and doravirine in combination and clinical outcomes among persons with HIV infection (PWH) receiving care at the Washington DC VAMC. METHODS: A quality improvement initiative utilized the clinical case registry to identify all PWH receiving both dolutegravir and doravirine. We conducted chart review to examine (a) the reasons for switch from other ART to dolutegravir and doravirine, and comorbidities, HIV resistance mutations or drug interactions precluding the use of standard ART, (b) adverse events or side effects and (c) achievement of virologic suppression. RESULTS: A case registry search revealed 21 individuals receiving combination dolutegravir doravirine from 2018–2020 (Table 1 and Figure 1). Side effects were not noted except one patient developed mild diarrhea that improved with continuation of therapy. Four patients were hospitalized during the follow-up period for reasons unrelated to the medications. One patient who was admitted to the ICU with shock and multi-organ failure was switched on admission but died four days later and therefore was not included in the analysis of viral outcome (Table 2). One patient had cardiac arrest following missed dialysis, hyperkalemia and rectal hemorrhage from metastatic rectal cancer. Table 1: Patient Demographics. [Image: see text] Figure 1: Reasons for Switching to Dolutegravir with Doravirine. [Image: see text] Table 2: Virologic Control Before and After Switching to Dolutegravir with Doravirine. [Image: see text] CONCLUSION: In an era of abundant ART options, we identified a subset of older PWH whose treatment options are defined by extensive comorbidities, viral resistance, and medication interactions or toxicities. Doravirine is attractive for this population as it can be used in renal impairment, moderate hepatic impairment, is unaffected by timing of meals, and (unlike rilpivirine) has no interaction with proton pump inhibitors. Dolutegravir is included in NRTI-sparing regimens that HHS guidelines suggest should be considered in older PWH, especially with CKD. We found that dolutegravir with doravirine is well tolerated, and achieves virologic suppression in the majority of PWH, indicating this combination is useful when other ART options cannot be used. DISCLOSURES: All Authors: No reported disclosures
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spelling pubmed-77775082021-01-07 1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable Denyer, Rachel Zemskova, Julie Beatty, Daniel Benator, Debra A Open Forum Infect Dis Poster Abstracts BACKGROUND: A drug-drug interaction study between dolutegravir and doravirine in healthy volunteers found no evidence of untoward interaction. Whilst we hypothesize that the combination would be safe and effective, there is no supportive clinical data. We aimed to assess the rationale for use of dolutegravir and doravirine in combination and clinical outcomes among persons with HIV infection (PWH) receiving care at the Washington DC VAMC. METHODS: A quality improvement initiative utilized the clinical case registry to identify all PWH receiving both dolutegravir and doravirine. We conducted chart review to examine (a) the reasons for switch from other ART to dolutegravir and doravirine, and comorbidities, HIV resistance mutations or drug interactions precluding the use of standard ART, (b) adverse events or side effects and (c) achievement of virologic suppression. RESULTS: A case registry search revealed 21 individuals receiving combination dolutegravir doravirine from 2018–2020 (Table 1 and Figure 1). Side effects were not noted except one patient developed mild diarrhea that improved with continuation of therapy. Four patients were hospitalized during the follow-up period for reasons unrelated to the medications. One patient who was admitted to the ICU with shock and multi-organ failure was switched on admission but died four days later and therefore was not included in the analysis of viral outcome (Table 2). One patient had cardiac arrest following missed dialysis, hyperkalemia and rectal hemorrhage from metastatic rectal cancer. Table 1: Patient Demographics. [Image: see text] Figure 1: Reasons for Switching to Dolutegravir with Doravirine. [Image: see text] Table 2: Virologic Control Before and After Switching to Dolutegravir with Doravirine. [Image: see text] CONCLUSION: In an era of abundant ART options, we identified a subset of older PWH whose treatment options are defined by extensive comorbidities, viral resistance, and medication interactions or toxicities. Doravirine is attractive for this population as it can be used in renal impairment, moderate hepatic impairment, is unaffected by timing of meals, and (unlike rilpivirine) has no interaction with proton pump inhibitors. Dolutegravir is included in NRTI-sparing regimens that HHS guidelines suggest should be considered in older PWH, especially with CKD. We found that dolutegravir with doravirine is well tolerated, and achieves virologic suppression in the majority of PWH, indicating this combination is useful when other ART options cannot be used. DISCLOSURES: All Authors: No reported disclosures Oxford University Press 2020-12-31 /pmc/articles/PMC7777508/ http://dx.doi.org/10.1093/ofid/ofaa439.1195 Text en © The Author 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Poster Abstracts
Denyer, Rachel
Zemskova, Julie
Beatty, Daniel
Benator, Debra A
1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable
title 1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable
title_full 1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable
title_fullStr 1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable
title_full_unstemmed 1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable
title_short 1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable
title_sort 1009. dolutegravir and doravirine in combination: when standard antiretroviral regimens are unacceptable
topic Poster Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7777508/
http://dx.doi.org/10.1093/ofid/ofaa439.1195
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