title: Moving away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE)--agents that concern prescribers and patients: a feasibility study and call for a trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
authors: Amit C
authors: AC
authors: Achhra
authors: The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
authors: Mark A
authors: MA
authors: Boyd
authors: The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
authors: Matthew G
authors: MG
authors: Law
authors: The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
authors: Gail V
authors: GV
authors: Matthews
authors: The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
authors: Anthony D
authors: AD
authors: Kelleher
authors: The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
authors: David A
authors: DA
authors: Cooper
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068698:Tenofovir; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003510:Cyclohexanes; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D000077592:Maraviroc; D063065:Organophosphonates; D019438:Ritonavir; D000068698:Tenofovir; D014230:Triazoles; D000099227:Abacavir; C098320:efavirenz