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Observational Study
. 2014 Jun 26;9(6):e99530.
doi: 10.1371/journal.pone.0099530. eCollection 2014.

Moving away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE)--agents that concern prescribers and patients: a feasibility study and call for a trial

Amit C Achhra  1 , Mark A Boyd  1 , Matthew G Law  1 , Gail V Matthews  1 , Anthony D Kelleher  1 , David A Cooper  1
Affiliations
Observational Study

Moving away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE)--agents that concern prescribers and patients: a feasibility study and call for a trial

Amit C Achhra et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: ACA is the recipient of Gilead Australia Fellowship. ADK has received honorarium/consultancy/travel grant from ViiV and Merck. MAB has received honorarium/consultancy/grants (unrelated to this project) from Gilead, BMS, Merck, AbbVie, Boehringer-Ingelheim and Jannsen. GVM has received honorarium/consultancy/grants (unrelated to this project) from Gilead, BMS, Roche, Janssen, MSD. Others: None to declare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Proposed trial for evaluating RATE-sparing options.
See this image and copyright information in PMC

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