title: Effectiveness and cost-effectiveness of a nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial.
abstract: No high-quality trials have provided evidence of effectiveness and cost-effectiveness of HIV treatment adherence intervention strategies. We therefore examined the effectiveness and cost-effectiveness of the Adherence Improving self-Management Strategy (AIMS) compared with treatment as usual.
  
  
  
  We did a pragmatic, multicentre, open-label, randomised controlled trial in seven HIV clinics at academic and non-academic hospitals in the Netherlands. Eligible participants were patients with HIV who were either treatment experienced (ie, with ≥9 months on combination antiretroviral therapy [ART] and at risk of viral rebound) or treatment-naive patients initiating their first combination ART regimen. We randomly assigned participants (1:1) to either AIMS or treatment as usual (ie, containing a range of common adherence intervention strategies) using a computer-generated randomisation table. Randomisation was stratified by treatment experience (experienced vs naive) and included block randomisation at nurse level with randomly ordered blocks of size four, six, and eight. 21 HIV nurses from the participating clinics received three training sessions of 6 h each (18 h in total) on AIMS and a 1·5 h booster training session at the clinic (two to three nurses per session) after each nurse had seen two to three patients. AIMS was delivered by nurses during routine clinic visits. We did mixed-effects, intent-to-treat analyses to examine treatment effects on the primary outcome of log10viral load collected at months 5, 10, and 15. The viral load results were exponentiated (with base 10) for easier interpretation. Using cohort data from 7347 Dutch patients with HIV to calculate the natural course of illness, we developed a lifetime Markov model to estimate the primary economic outcome of lifetime societal costs per quality-adjusted life-years (QALYs) gained. This trial is registered at ClinicalTrials.gov (number NCT01429142).
  
  
  
  We recruited participants between Sept 1, 2011, and April 2, 2013; the last patient completed the study on June 16, 2014. The intent-to-treat sample comprised 221 patients; 109 assigned to AIMS and 112 to treatment as usual. Across the three timepoints (months 5, 10, and 15), log viral load was 1·26 times higher (95% CI 1·04-1·52) in the treatment-as-usual group (estimated marginal mean 44·5 copies per mL [95% CI 35·5-55·9]) than in the AIMS group (estimated marginal mean 35·4 copies per mL [29·9-42·0]). Additionally, AIMS was cost-effective (ie, dominant: cheaper and more effective) since it reduced lifetime societal costs by €592 per patient and increased QALYs by 0·034 per patient.
  
  
  
  Findings from preparatory studies have shown that AIMS is acceptable, feasible to deliver in routine care, and has reproducible effects on medication adherence. In this study, AIMS reduced viral load, increased QALYs, and saved resources. Implementation of AIMS in routine clinical HIV care is therefore recommended.
  
  
  
  Netherlands Organisation for Health Research and Development.
authors.affiliation: University of Aberdeen, Institute of Applied Health Sciences, Aberdeen, UK; Amsterdam School of Communication Research (ASCoR), University of Amsterdam, Amsterdam, Netherlands. Electronic address: M.debruin@abdn.ac.uk.
authors.forename: Marijn
authors.initials: M
authors.lastname: de Bruin
authors.affiliation: Amsterdam School of Communication Research (ASCoR), University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Edwin J M
authors.initials: EJM
authors.lastname: Oberjé
authors.affiliation: Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, Netherlands.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Viechtbauer
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Centre Amsterdam, Amsterdam, Netherlands.
authors.forename: Hans-Erik
authors.initials: HE
authors.lastname: Nobel
authors.affiliation: Department of Health Services Research, CAPHRI School for Public Health & Primary Care, Maastricht University, Maastricht, Netherlands.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Hiligsmann
authors.affiliation: Haga Hospital, The Hague, Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van Nieuwkoop
authors.affiliation: Sint Lucas Andreas Hospital, Amsterdam, Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Veenstra
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Centre Amsterdam, Amsterdam, Netherlands.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Pijnappel
authors.affiliation: Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Kroon
authors.affiliation: Erasmus Medical Centre, Rotterdam, Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: van Zonneveld
authors.affiliation: Isala clinics, Zwolle, Netherlands.
authors.forename: Paul H P
authors.initials: PHP
authors.lastname: Groeneveld
authors.affiliation: Slotervaart Hospital, Amsterdam, Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Broekhuizen
authors.affiliation: Department of Health Services Research, CAPHRI School for Public Health & Primary Care, Maastricht University, Maastricht, Netherlands; Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Center of Economic Evaluations, Utrecht, Netherlands.
authors.forename: Silvia M A A
authors.initials: SMAA
authors.lastname: Evers
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Centre Amsterdam, Amsterdam, Netherlands.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000451:nursing*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009426:Netherlands; D024802:Nurse's Role; D019057:Quality-Adjusted Life Years; D012648:Self Care / Q000379:methods; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents