Cargando…

Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial

OBJECTIVES: Regimens sparing RATE (ritonavir, abacavir, tenofovir, efavirienz) agents might have better long-term safety. We conducted a feasibility exercise to assess the potential for a randomised trial evaluating RATE-sparing regimens. DESIGN: Observational. METHODS: We first calculated RATE-spar...

Descripción completa

Detalles Bibliográficos
Autores principales: Achhra, Amit C., Boyd, Mark A., Law, Matthew G., Matthews, Gail V., Kelleher, Anthony D., Cooper, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072535/
https://www.ncbi.nlm.nih.gov/pubmed/24968324
http://dx.doi.org/10.1371/journal.pone.0099530
_version_ 1782322976986759168
author Achhra, Amit C.
Boyd, Mark A.
Law, Matthew G.
Matthews, Gail V.
Kelleher, Anthony D.
Cooper, David A.
author_facet Achhra, Amit C.
Boyd, Mark A.
Law, Matthew G.
Matthews, Gail V.
Kelleher, Anthony D.
Cooper, David A.
author_sort Achhra, Amit C.
collection PubMed
description OBJECTIVES: Regimens sparing RATE (ritonavir, abacavir, tenofovir, efavirienz) agents might have better long-term safety. We conducted a feasibility exercise to assess the potential for a randomised trial evaluating RATE-sparing regimens. DESIGN: Observational. METHODS: We first calculated RATE-sparing options available to an average patient receiving RATE agents. We reviewed treatment history and all resistance assays from patients attending the St. Vincent’s Hospital (Sydney) clinic and receiving ≥2 RATE agents (n = 120). A viable RATE-sparing regimen with 2 or 3 fully-active agents was constructed from the following six ‘safer’ agents: rilpivirine or etravirine; atazanavir; raltegravir; maraviroc; and lamivudine. Activity for each drug was predicted as 1 (full-activity), 0.5 or 0 (no activity) using the Stanford mutation database. The utility of maraviroc was calculated assuming both maraviroc activity and inactivity where unknown. The analysis was restricted to regimens for which supporting evidence was identified in the literature or conference proceedings. Finally, we calculated the proportion of patients in the nationally representative Australian HIV Observational Database (AHOD) cohort receiving ≥2 RATE agents (n = 1473) to measure the potential population-level uptake of RATE-sparing agents. RESULTS: Assuming full maraviroc activity, 117(97.5%) and 107(89.2%) individuals had at least one option with 2 or 3 active RATE-sparing agents, respectively. Assuming no maraviroc activity this decreased to 113(94.2%) and 104(86.7%), respectively. In AHOD, 837(56.8%) patients were receiving ≥2 RATE agents. CONCLUSION: Feasible treatment switch options sparing RATE agents exist for the majority of patients. Understanding the pros and cons of switching stable patients onto new RATE-sparing regimens requires evidence derived from randomised controlled trials.
format Online
Article
Text
id pubmed-4072535
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-40725352014-07-02 Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial Achhra, Amit C. Boyd, Mark A. Law, Matthew G. Matthews, Gail V. Kelleher, Anthony D. Cooper, David A. PLoS One Research Article OBJECTIVES: Regimens sparing RATE (ritonavir, abacavir, tenofovir, efavirienz) agents might have better long-term safety. We conducted a feasibility exercise to assess the potential for a randomised trial evaluating RATE-sparing regimens. DESIGN: Observational. METHODS: We first calculated RATE-sparing options available to an average patient receiving RATE agents. We reviewed treatment history and all resistance assays from patients attending the St. Vincent’s Hospital (Sydney) clinic and receiving ≥2 RATE agents (n = 120). A viable RATE-sparing regimen with 2 or 3 fully-active agents was constructed from the following six ‘safer’ agents: rilpivirine or etravirine; atazanavir; raltegravir; maraviroc; and lamivudine. Activity for each drug was predicted as 1 (full-activity), 0.5 or 0 (no activity) using the Stanford mutation database. The utility of maraviroc was calculated assuming both maraviroc activity and inactivity where unknown. The analysis was restricted to regimens for which supporting evidence was identified in the literature or conference proceedings. Finally, we calculated the proportion of patients in the nationally representative Australian HIV Observational Database (AHOD) cohort receiving ≥2 RATE agents (n = 1473) to measure the potential population-level uptake of RATE-sparing agents. RESULTS: Assuming full maraviroc activity, 117(97.5%) and 107(89.2%) individuals had at least one option with 2 or 3 active RATE-sparing agents, respectively. Assuming no maraviroc activity this decreased to 113(94.2%) and 104(86.7%), respectively. In AHOD, 837(56.8%) patients were receiving ≥2 RATE agents. CONCLUSION: Feasible treatment switch options sparing RATE agents exist for the majority of patients. Understanding the pros and cons of switching stable patients onto new RATE-sparing regimens requires evidence derived from randomised controlled trials. Public Library of Science 2014-06-26 /pmc/articles/PMC4072535/ /pubmed/24968324 http://dx.doi.org/10.1371/journal.pone.0099530 Text en © 2014 Achhra et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Achhra, Amit C.
Boyd, Mark A.
Law, Matthew G.
Matthews, Gail V.
Kelleher, Anthony D.
Cooper, David A.
Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial
title Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial
title_full Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial
title_fullStr Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial
title_full_unstemmed Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial
title_short Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial
title_sort moving away from ritonavir, abacavir, tenofovir, and efavirenz (rate) - agents that concern prescribers and patients: a feasibility study and call for a trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072535/
https://www.ncbi.nlm.nih.gov/pubmed/24968324
http://dx.doi.org/10.1371/journal.pone.0099530
work_keys_str_mv AT achhraamitc movingawayfromritonavirabacavirtenofovirandefavirenzrateagentsthatconcernprescribersandpatientsafeasibilitystudyandcallforatrial
AT boydmarka movingawayfromritonavirabacavirtenofovirandefavirenzrateagentsthatconcernprescribersandpatientsafeasibilitystudyandcallforatrial
AT lawmatthewg movingawayfromritonavirabacavirtenofovirandefavirenzrateagentsthatconcernprescribersandpatientsafeasibilitystudyandcallforatrial
AT matthewsgailv movingawayfromritonavirabacavirtenofovirandefavirenzrateagentsthatconcernprescribersandpatientsafeasibilitystudyandcallforatrial
AT kelleheranthonyd movingawayfromritonavirabacavirtenofovirandefavirenzrateagentsthatconcernprescribersandpatientsafeasibilitystudyandcallforatrial
AT cooperdavida movingawayfromritonavirabacavirtenofovirandefavirenzrateagentsthatconcernprescribersandpatientsafeasibilitystudyandcallforatrial