A randomised controlled trial conducted in the Netherlands showed that a nurse-led antiretroviral therapy adherence support programme had a significant effect on viral load and was cost-effective.
The antiretroviral therapy or ART adherence support study has been hailed as “an outstanding addition to the scientific literature on adherence”.
The research led by Professor Marijn de Bruin at the University of Aberdeen’s Institute of Applied Health Science and the Amsterdam School of Communication Research (ASCoR) at the University of Amsterdam, was conducted in the Netherlands between 2011 and 2014 and involved people already taking ART who were at risk of virological failure, as well as people starting HIV therapy for the first time.
“This is the first randomised controlled trial of an HIV treatment adherence intervention that showed a clinically meaningful effect on viral load as well as cost-effectiveness,” comment the investigators. The authors of an accompanying editorial state that the study “paves the way for the next generation of ART adherence research.”
Thanks to ART, many people living with HIV now have a near-normal life expectancy. Modern anti-HIV drugs are potent, have mild side-effect profiles and are usually taken once daily. However, adherence remains a barrier to the long-term effectiveness of therapy.
No high-quality study has provided evidence of the effectiveness and cost-effectiveness of adherence support strategies.
Investigators in the Netherlands therefore designed the Adherence Improving Self-Management Strategy (AIMS). This nurse-led intervention was developed as long ago as 2003 and has previously been shown to be acceptable to patients and staff, to be feasible and to have an effect on viral load. But this research was limited as it took place in a single centre and had a short follow-up intervention (seven months).
Investigators now wanted to see if AIMS was effective and cost-effective in near real-world settings. They designed a multi-centre, randomised controlled study involving 221 people living with HIV recruited at seven clinics across the Netherlands.
The participants were randomly assigned to AIMS or to receive routine care. The AIMS intervention was provided by 21 specially trained nurses. Participants randomised to receive the AIMS intervention received:
A visual presentation of how drug concentrations vary with adherence patterns, and how this affects treatment outcomes. A MEMS-cap electronic pill bottle monitor to record adherence patterns; these reports could be printed out by the patient. Participants used the MEMS-cap for 4-8 weeks before the first session with the adherence nurse.
At the first meeting with the adherence nurse, they were shown a visual representation of seven adherence patterns recorded from MEMS-caps, ranging from excellent to poor, to help patients identify good adherence from their own records.
Patients were then asked to select the level of adherence they wished to achieve and to relate that to the information they had seen. Patients then selected an adherence goal to be achieved by the next visit. They were asked to indicate how confident they were of achieving the adherence goal on a visual 1-10 scale.
Adherence nurse and patient then discussed strategies for coping with adherence difficulties. These were written down as “if this happens, then…” Patients starting treatment for the first time were asked to identify five reasons for starting treatment and five concerns about starting treatment. These concerns were then addressed in discussion with the adherence nurse.
Subsequent sessions examined adherence patterns and reinforced goal-setting and problem-solving, with the aim of achieving the desired level of adherence within five months. Patients then aimed to maintain good adherence for the next ten months.
All these elements were presented in a one-to-one discussion between the adherence nurse and the patient.
Patients in the routine care study arm received an information leaflet together with a verbal explanation of how treatment works and the need for good adherence. Patients discussed when and how to take their medication with a nurse and discussed their adherence patterns with the nurse at subsequent visits. Nurses provided information on CD4 and viral load results to reinforce adherence or to identify potential problems. All patients could call the clinic regarding adherence problems or side effects.
Treatment-experienced patients (people who had been on ART for nine months or more) with at least one recent episode of viral breakthrough and patients starting ART for the first time were eligible for inclusion in the study.
Viral load was compared between the AIMS and routine care participants after 5, 10 and 15 months of follow-up. The investigators also calculated the cost-effectiveness of the intervention.
Most of the participants were male and white and the mean age was 44 years. About half the participants were treatment experienced and of those, a third had a detectable viral load at baseline.
AIMS participants received 85% of planned interventions, during which two-thirds of intervention elements were delivered. The main reason for non-delivery was an improvement in adherence since the last follow-up visit, or because plans made during the last session were still relevant.
The average duration of clinic visits was 29 minutes for AIMS participants and 19 minutes for participants receiving routine care.
At all three follow-up points, viral load was 26% higher among people receiving routine care compared to those provided with AIMS (mean viral load 44.5 vs 35.4 copies/ml). 9% of the AIM group experienced virological failure of treatment (detectable viral load at two consecutive follow-up visits) compared to 23% of the routine care group. Odds of treatment failure were three times higher for people receiving routine care (OR = 2.99; 95% CI 1.21-7.38).
There was no difference in viral load response according to which nurse had delivered the AIMS intervention or routine care.
AIMS was also shown to be cost-effective, reducing lifetime costs by €592 per person and increased quality-adjusted life-years (QALYS) by 0.034 per person.
“AIMS requires few resources, is feasible to deliver in routine care, and is acceptable to health-care providers and patients,” write the authors. “The AIMS intervention should be scalable and the results generalisable to the wider population of patients and HIV clinics – at least in high-income settings. Implementation of AIMS in routine HIV clinical care is therefore strongly recommended.”
The authors of the editorial call for further implementation research, but urge that this needs to be conducted as a matter of urgency.
Background: 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.
Methods: 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 log10 viral 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).
Findings: 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.
Interpretation: 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.
Marijn de Bruin, Edwin J M Oberjé, Wolfgang Viechtbauer, Hans-Erik Nobel, Mickaël Hiligsmann, Cees van Nieuwkoop, Jan Veenstra, Frank J Pijnappel, Frank P Kroon, Laura van Zonneveld, Paul H P Groeneveld, Marjolein van Broekhuizen, Silvia M A A Evers, Jan M Prins