NIHR Signal Individual support of nurses using electronic medicine monitors can improve HIV treatment

Published on 10 October 2017

Use of electronic pill bottles that record when they are opened and follow-up discussion of the printed readouts with nurses improved HIV outcomes. It is thought that patients became more reliable in taking the medication, which can have complicated scheduling. Overall, the HIV virus in the blood and the risk of treatment failure were lower in the group of patients who had access to this intervention compared to regular care.

In addition to being more effective, the programme also reduced the estimated lifetime cost and disease burden per patient, considering quality and quantity of life lived.

The readouts were used to help focus attention on any patterns of medication usage so that strategies could be discussed to improve adherence. As non-adherence is the main barrier to effective management of HIV, any measures that improve it are welcomed. However, the intervention tested here requires several hours of training for the nurses delivering it and may not be that easy to introduce in practice. Evaluation of the approach in non-trial settings is necessary before wider implementation.

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Why was this study needed?

HIV infection is diagnosed in 11.4 per 100,000 people per year in the UK, higher than the average rate of 6.3 in most countries in Western Europe. In 2015, over 100,000 people were estimated to live with HIV in the UK, and almost 89,000 received HIV care.

Effective treatment with antiretroviral therapy can provide life expectancy rates similar to non-infected individuals and considerably reduce the risk of transmission. This therapy needs to be taken at roughly the same time each day though, which can be difficult. In 2012, 32% of 2,704 participants in a research study on socioeconomic status and HIV treatment in the UK self-reported non-adherence to treatment. Non-adherence is an obstacle to achieving the best health outcomes and for prevention of the development and transmission of resistant viruses.

This trial assessed whether a support programme delivered by nurses using electronic medication monitors improved the effectiveness of HIV treatment.

What did this study do?

This randomised controlled trial assigned 109 adults to the Adherence Improving self-Management Strategy and 112 adults to regular care in seven HIV clinics in the Netherlands. Participants were either initiating their first combination treatment or already on this treatment but at risk of increasing viral load in the blood, due to poor adherence.

The strategy group were given an electronic bottle cap which records the date and time it is opened. Printed reports of their adherence were used during usual clinic appointments with a nurse to identify patterns and create solutions. Twenty-one nurses delivered the strategy and device. Nurses received four training sessions to a total of almost 20 hours.

The regular care group had the same number of appointments, on average 3.2 over 15 months. This did not include initial monitoring for half of the participants in each group who were starting antiretroviral therapy.

Though neither participants nor staff could be blinded to treatment group, outcome measures were objective so the results should be reliable.

What did it find?

  • Across the three time points, five, 10 and 15 months, viral load was 1.26 times higher in the regular care group than in the Adherence Improving Strategy group (95% confidence interval [CI] 1.04 to 1.52). Viral load (adjusted) was 44.5 copies per mL for the regular care group (95% CI 35.5 to 55.9) compared to 35.4 copies per mL for the strategy group (95% CI 29.9 to 42.0).
  • Treatment failure - a detectable viral load on two consecutive visits - occurred in 9% of the strategy group compared to 23% of the regular care group (odds ratio 2.99, 95% CI 1.21 to 7.38).
  • At the third follow-up, immune system capacity, measured through average CD4 cell counts, was at reasonable levels in both groups though slightly better in the strategy group (mean difference 39.39 cells per L, 95% CI 0.10 to 78.67).
  • The delivery of regular care took on average 18.8 minutes and that of the strategy 29.1 minutes, with a total difference of 35 minutes over the follow-up.
  • The strategy and device were estimated to reduce lifetime societal costs by €592 per patient and slightly increase quality of life per patient (increase in quality-adjusted life years of 0.034 per patient).

What does current guidance say on this issue?

The 2016 interim update of the British HIV Association guideline for the treatment of HIV recommends assessing and discussing adherence and potential barriers whenever antiretroviral therapy is discussed, prescribed or dispensed. It recommends discussing perceptual barriers, such as beliefs and preferences, and/or practical barriers, such as resource limitation.

The guideline further recommends that individuals experiencing difficulties with adherence are offered additional support from staff and/or organisations offering peer support. Individuals with several episodes of treatment failure with or without extensive HIV drug resistance should receive intensive adherence support at the start of a new ART and at regular intervals.

What are the implications?

The results of this trial indicate that adherence to antiretroviral therapy can be improved by nurses aided by objective measurements of medicine use. This complex intervention led to reduced HIV load and potential health cost savings. The approach requires training for the nurses, and some added time to deliver it. The interest and enthusiasm of the clinic staff seem important.

There is also the issue of acceptability – 60% of people attending the participating HIV clinics did not want to be involved in the study. While this suggests some resistance, it could be that patients would accept this intervention if it was part of regular practice and not part of clinical research.

Citation and Funding

de Bruin M, Oberjé EJ, Viechtbauer W, et al. Effectiveness and cost-effectiveness of a
nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial
. Lancet Infect Dis. 2017;17(6):595-604.

This project was funded by the Netherlands Organisation for Health Research and Development (ZonMW; grant number 171002208).

Bibliography

BHIVA. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015 (2016 interim update). London: British HIV Association; 2016.

Burch LS, Smith CJ, Anderson J, et al. Socioeconomic status and treatment outcomes for individuals with HIV on antiretroviraltreatment in the UK: cross-sectional and longitudinal analyses. Lancet Public Health. 2016;1(1):e26-36.

Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed? A novel assessment technique. JAMA. 1989;261(11):3273-7.

NAT. HIV in the UK statistics - 2015. London: National AIDS Trust; 2015.

NHS Choices. HIV and AIDS. London: Department of Health; 2014.

PHE. HIV in the UK - 2016 report. London: Public Health England; 2016.

Simoni JM, Aunon FM, Kemp CG, et al. Implementation research on HIV adherence interventions: no time to wait. Lancet Infect Dis. 2017;17(6):564-65.

Why was this study needed?

HIV infection is diagnosed in 11.4 per 100,000 people per year in the UK, higher than the average rate of 6.3 in most countries in Western Europe. In 2015, over 100,000 people were estimated to live with HIV in the UK, and almost 89,000 received HIV care.

Effective treatment with antiretroviral therapy can provide life expectancy rates similar to non-infected individuals and considerably reduce the risk of transmission. This therapy needs to be taken at roughly the same time each day though, which can be difficult. In 2012, 32% of 2,704 participants in a research study on socioeconomic status and HIV treatment in the UK self-reported non-adherence to treatment. Non-adherence is an obstacle to achieving the best health outcomes and for prevention of the development and transmission of resistant viruses.

This trial assessed whether a support programme delivered by nurses using electronic medication monitors improved the effectiveness of HIV treatment.

What did this study do?

This randomised controlled trial assigned 109 adults to the Adherence Improving self-Management Strategy and 112 adults to regular care in seven HIV clinics in the Netherlands. Participants were either initiating their first combination treatment or already on this treatment but at risk of increasing viral load in the blood, due to poor adherence.

The strategy group were given an electronic bottle cap which records the date and time it is opened. Printed reports of their adherence were used during usual clinic appointments with a nurse to identify patterns and create solutions. Twenty-one nurses delivered the strategy and device. Nurses received four training sessions to a total of almost 20 hours.

The regular care group had the same number of appointments, on average 3.2 over 15 months. This did not include initial monitoring for half of the participants in each group who were starting antiretroviral therapy.

Though neither participants nor staff could be blinded to treatment group, outcome measures were objective so the results should be reliable.

What did it find?

  • Across the three time points, five, 10 and 15 months, viral load was 1.26 times higher in the regular care group than in the Adherence Improving Strategy group (95% confidence interval [CI] 1.04 to 1.52). Viral load (adjusted) was 44.5 copies per mL for the regular care group (95% CI 35.5 to 55.9) compared to 35.4 copies per mL for the strategy group (95% CI 29.9 to 42.0).
  • Treatment failure - a detectable viral load on two consecutive visits - occurred in 9% of the strategy group compared to 23% of the regular care group (odds ratio 2.99, 95% CI 1.21 to 7.38).
  • At the third follow-up, immune system capacity, measured through average CD4 cell counts, was at reasonable levels in both groups though slightly better in the strategy group (mean difference 39.39 cells per L, 95% CI 0.10 to 78.67).
  • The delivery of regular care took on average 18.8 minutes and that of the strategy 29.1 minutes, with a total difference of 35 minutes over the follow-up.
  • The strategy and device were estimated to reduce lifetime societal costs by €592 per patient and slightly increase quality of life per patient (increase in quality-adjusted life years of 0.034 per patient).

What does current guidance say on this issue?

The 2016 interim update of the British HIV Association guideline for the treatment of HIV recommends assessing and discussing adherence and potential barriers whenever antiretroviral therapy is discussed, prescribed or dispensed. It recommends discussing perceptual barriers, such as beliefs and preferences, and/or practical barriers, such as resource limitation.

The guideline further recommends that individuals experiencing difficulties with adherence are offered additional support from staff and/or organisations offering peer support. Individuals with several episodes of treatment failure with or without extensive HIV drug resistance should receive intensive adherence support at the start of a new ART and at regular intervals.

What are the implications?

The results of this trial indicate that adherence to antiretroviral therapy can be improved by nurses aided by objective measurements of medicine use. This complex intervention led to reduced HIV load and potential health cost savings. The approach requires training for the nurses, and some added time to deliver it. The interest and enthusiasm of the clinic staff seem important.

There is also the issue of acceptability – 60% of people attending the participating HIV clinics did not want to be involved in the study. While this suggests some resistance, it could be that patients would accept this intervention if it was part of regular practice and not part of clinical research.

Citation and Funding

de Bruin M, Oberjé EJ, Viechtbauer W, et al. Effectiveness and cost-effectiveness of a
nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial
. Lancet Infect Dis. 2017;17(6):595-604.

This project was funded by the Netherlands Organisation for Health Research and Development (ZonMW; grant number 171002208).

Bibliography

BHIVA. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015 (2016 interim update). London: British HIV Association; 2016.

Burch LS, Smith CJ, Anderson J, et al. Socioeconomic status and treatment outcomes for individuals with HIV on antiretroviraltreatment in the UK: cross-sectional and longitudinal analyses. Lancet Public Health. 2016;1(1):e26-36.

Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed? A novel assessment technique. JAMA. 1989;261(11):3273-7.

NAT. HIV in the UK statistics - 2015. London: National AIDS Trust; 2015.

NHS Choices. HIV and AIDS. London: Department of Health; 2014.

PHE. HIV in the UK - 2016 report. London: Public Health England; 2016.

Simoni JM, Aunon FM, Kemp CG, et al. Implementation research on HIV adherence interventions: no time to wait. Lancet Infect Dis. 2017;17(6):564-65.

Effectiveness and cost-effectiveness of a nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial

Published on 7 March 2017

de Bruin, M.,Oberje, E. J.,Viechtbauer, W.,Nobel, H. E.,Hiligsmann, M.,van Nieuwkoop, C.,Veenstra, J.,Pijnappel, F. J.,Kroon, F. P.,van Zonneveld, L.,Groeneveld, P. H.,van Broekhuizen, M.,Evers, S. M.,Prins, J. M.

Lancet Infect Dis , 2017

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 euro592 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. FUNDING: Netherlands Organisation for Health Research and Development.

Expert commentary

It seems a ‘no-brainer’ that ways to increase how well people with HIV take their treatment should result in better outcomes. Surprisingly data to support such interventions are lacking.

This study goes some way to answering this question. Electronic medicine monitors were used to record when pill bottles were opened. Using this information, nurses delivered advice on how patients could improve adherence to their HIV medication. Those using electronic medicine monitors and individualised adherence advice had better treatment responses than those receiving ‘treatment as usual’.

The challenge is how to incorporate such interventions into routine clinical care.

Dr Chris Taylor, HIV Consultant, Kings College Hospital