Pop-Eleches C, Thirumurthy H, Habyarimana JP, Zivin JG, Goldstein MP, de Walque D, Mackeen L, Haberer J, Kimaiyo S, Sidle J, Ngare D, Bangsberg DR. Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders. AIDS. 2011 February 10. [Epub ahead of print]
Poor adherence to antiretroviral therapy (ART) is associated with the development of drug resistance, disease progression and death.(1, 2, 3, 4) The increasingly well-developed telecommunications systems and the widespread use of cellular phones in resource-constrained areas present an opportunity to test the efficacy of short message service (SMS, or text messages) reminders for ART adherence.
To test the efficacy of SMS reminders for ART adherence.
A single rural health clinic in Nyanza Province, Kenya.
Randomized controlled trial.
There were 735 patients recruited, of whom 720 (97.9%) consented to participate. There were 431 participants included in the analysis. One hundred thirty-nine subjects were randomized to the control group. Participation in the four intervention groups was essentially equal (range 70-74 subjects). Demographic characteristics, ART regimens and change in regimen during the study did not differ between intervention and control groups.
Sixteen percent of participants were lost to follow-up (defined as 90 days or more from the last Medication Event Monitoring System [MEMS]-recorded opening). Loss to follow-up rates did not differ between groups. Sixty-nine subjects lost their phones and 51 changed their phone numbers during the study. Twenty-five participants had their MEMS cap replaced because of loss or malfunction and the distribution of these subjects across study arms did not differ significantly.
The adherence in the control group retained in care was 75.8%, and declined over the study period. Between weeks one and 12, 60% of participants achieved 90% adherence and for the period of weeks 37-48, 46% achieved 90% adherence (p=0.007). Ninety percent of the control group had at least one treatment interruption.
The intent-to-treat analysis of daily and weekly reminders found that the fraction of participants with adherence of at least 90% in the two groups receiving weekly reminders was significantly higher than the control group (53 vs. 40%, p=0.03). The fraction of participants with adherence of at least 90% was not significantly greater for those receiving daily reminders than the control group (41 vs. 40%, p=0.92). Comparing short and long reminders showed that the fraction of participants achieving adherence of at least 90% was 47% in the two groups that received long reminders, compared with 40% in the control group (p=0.24). Similarly, the two groups receiving short reminders achieved adherence of at least 90% at rates that were not significantly higher than the control group (47 vs. 40%, p=0.24).
The per protocol analysis found that both weekly MSM groups had a lower proportion of participants who met the treatment interruption outcome than participants in the control group (80 vs. 88%, p=0.08).
Text messaging may help improve adherence compared to no intervention.
This study met the criteria for a high quality randomized control trial; allocation was truly random, developed offsite with proper concealment, the assessor of the outcome, though not explicitly stated, appears to have been blinded to group assignment based on the description of assessing the outcome, loss to follow-up was accounted for and acceptable, and an intent-to-treat approach was applied to the analysis.
Development of methods to improve adherence for person receiving ART is critical to achieving substantive declines in morbidity and mortality and in minimizing the development of resistance. Although the intervention tested in this study showed some effect, the degree of adherence remained low. It is interesting to note that a simple text reminder was as effective as longer, more supportive messages. As such, it seems that inadequate adherence may simply be due to forgetting to take the medication and not to other aspects that may relate to medication and illness.
Of note is that weekly, not daily reminders were effective. Frequent messaging may lead to habituation in which the participant became so accustomed to the messages that they were no longer noticed. Although there was some effect of SMS at reducing declines in adherence over time, electronic monitoring has been shown to be more effective. Real-time adherence using wireless technology may allow for a timed link between missed doses and reminders which may in turn be more effective than weekly, non-specific text messages. The continued exploration of methods to improve adherence and in particular those that can be successfully used in rural areas and that are not labor-intensive should continue to be pursued.
- Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS. The impact of adherence on CD4 cell count responses among HIV-infected patients. J Acquir Immune Defic Syndr 2004; 35:261-268.
- Bangsberg DR, Perry S, Charlebois ED, Clark RA, Roberston M,Zolopa AR, Moss A. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 2001;15:1181-1183.
- Oyugi JH, Byakika-Tusiime J, Charlebois ED, Kityo C, Mugerwa R, Mugyenyi P, Bangsberg DR. Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting. J Acquir Immune Defic Syndr 2004; 36:1100-1102.
- Bangsberg DR, Deeks SG. Spending more to save more: interventions to promote adherence. Ann Intern Med 2010; 152:54-56; W-13.