The success of antiretroviral therapy (ART) has made HIV infection a manageable, chronic condition [
There are several ways to measure medication adherence, such as pill counts, patient self-reports, pharmacy refill, and electronic monitors [
A digital medication program (DMP) (Figure
Digital medicine program.
Coencapsulation of antiretrovirals.
In this study, our aim was to describe and analyze the perception and attitudes of PLWH and HIV HCPs towards medication adherence in general and real-time medication adherence with a focus on the DMP.
PLWH were recruited as part of an open-label pilot study preceding an ongoing clinical trial (trial registration number is
The recruitment of PLWH who participated in the pilot DMP study and HIV HCPs was conducted at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, a research institute of a safety net hospital in Los Angeles, California, via purposive sampling [
Each patient was paid $50 compensation for each DMP pilot study visit (of the three interviews included in the qualitative study, one was conducted during a face-to-face DMP study visit and was compensated, and the rest were conducted over the phone).
HIV HCPs working in the clinic where the DMP pilot study was conducted were recruited through convenience sampling for enrollment in a qualitative interview study by sending them informational emails about the study and follow-up reminder emails to nonresponders. Some of the HIV HCPs cared for PLWH enrolled in the DMP pilot study, and others did not have any PLWH enrolled in the study. The interviews were conducted by phone, and all participants agreed to audio-record the interviews. HCPs were interviewed using semistructured interviews using a semistructured interview guide (Appendix I-b), by the first author (S. K.) who is a pharmacist and a trained qualitative researcher. HCPs were not remunerated for participation.
Demographic and clinical characteristics of participants including PLWH and HIV HCPs were described using frequencies and percentages or median and interquartile ranges as appropriate. All analyses were completed using the R statistical package, version 3.3, and RStudio version 1.0.136 (R, a language and environment for statistical computing, R Foundation for Statistical Computing, Vienna, Austria (URL:
This study was approved by the UCLA-Harbor Institutional Review Board (IRB) committee (IRB number 30621-01, approved on 06/07/2017) and UCLA IRB committee (IRB number IRB#19-000910, approved on 6/13/2019). All collected data and information were stored on a password-protected computer and accessed only by the researchers. Full names of participants including PLWH and HIV HCPs were not recorded; they were assigned codes instead to ensure their anonymity.
Fifteen PLWH were included. One declined audio-recording. Baseline characteristics are presented in Table
Baseline characteristics of PLWH.
Characteristics ( | Mean (SD) or |
---|---|
Age, yrs | 50 (6.9) |
Gender | |
Male | 13 (86.7%) |
Race and ethnicity | |
Black | 7 (46.7%) |
Hispanic white | 6 (40.0%) |
Non-Hispanic white | 2 (13.3%) |
Self-identified major source of HIV infection | |
MSM | 9 (60.0%) |
Heterosexual sex | 5 (33.3%) |
IV drug use | 1 (6.7%) |
Duration since HIV diagnosis, yrs | 16 (7.0) |
Most recent CD4 count, cells/uL (min, max) | 774.2 (275, 1375) |
Most recent plasma HIV RNA | |
Undetectable (<20 copies/mL) | 10 (66.7%) |
Detectable (≥20 copies/mL) | 4 (26.7%) |
Unknown | 1 (6.7%) |
Self-reported missed doses in the past month | |
0 | 3 (20%) |
1-2 | 3 (20%) |
>2 | 5 (33.3%) |
Unknown | 4 (26.7%) |
Missed clinic visits in the past 6 months | |
None | 8 (53.3%) |
1 | 2 (13.3%) |
>1 | 3 (20%) |
Unknown | 2 (13.3%) |
Baseline characteristics of HIV healthcare providers.
Characteristics ( | Mean (SD) or |
---|---|
Age, yrs | 48 (14) |
Gender | |
Female | 4 (66.6%) |
Race and ethnicity | |
Asian | 3 (50%) |
Caucasian/white | 1 (16.7%) |
Hispanic/Latino | 1 (16.7%) |
Mixed race | 1 (16.7%) |
Years of work experience | 17 (12.5) |
Profession | |
Nurse practitioner | 4 (66.6%) |
Physician | 1 (16.6%) |
Resident | 1 (16.6%) |
Number of HIV + patients seen per week | 17 (8.2) |
Patients’ main source of HIV infection | |
MSM | 5 (83.3%) |
Heterosexual sex | 1 (16.6%) |
Number of patients using DMP | |
0 | 1 (16.6%) |
1–5 | 4 (66.6% |
>5 | 1 (16.6%) |
SD, standard deviation; MSM, men who have sex with men; HIV, human immunodeficiency virus; DMP, digital medicine program.
PLWH described several self-management techniques when asked how they usually took their medication and how they remembered to take it. For example, six participants described taking the medication at a specific time every day:
When PLWH were asked how they remember to get their medication from the pharmacy, for example, one described getting a call to pick it up:
PLWH were asked to describe their experiences using the DMP at day 3, week 2, and week 4 of the 16-week DMP pilot study. They were asked about specific aspects of the DMP including the coencapsulated pill, the patch, getting text messages, and using the tablet.
PLWH were asked about using the coencapsulated pills with the sensor in them. Five participants found it easy to take:
PLWH were asked about wearing the DMP patch. Seven participants found it inconvenient, for example, P7 (male, black, 51, and undetectable),
When asked about getting text messages, five PLWH found them helpful:
PLWH were given a tablet for use during the study as part of the DMP. Two participants had technical difficulties with using the tablet, for example, P15 (male, black, 53, undetectable),
PLWH were asked to describe the communication with the DMP technical team when they needed it. Those who had contacted them described the communication as follows: “
When asked to describe their overall experience with the DMP, six participants reported liking it:
PLWH were asked if they would recommend the DMP to others and why. All who offered an opinion recommended it:
HCPs described the barriers that their patients faced with ARV adherence. These included substance use, mental health issues, financial issues, homelessness, unacceptance of HIV diagnosis, and forgetfulness. Factors that facilitated ARV adherence included trusting their HCP, patient motivation and taking responsibility of their health, patients’ perceived health benefit, medications that are easy to take with simple one-pill-a-day regimens, proactive HCPs that remind patients about their clinic appointments, social and psychological support (from family and friends), and routinizing the patient’s pill-taking behavior, for example, taking the medication every day with breakfast or at bedtime. They also mentioned the use of aids to help with adherence such as alarms, pill organizers, and pill packs.
All HCPs knew of the DMP prior to the interview, as the DMP pilot study was conducted at their workplace. Five of six were treating patients in the DMP study. HCPs also seemed to understand how it works. When asked how the DMP helped their patient with ARV adherence, they mentioned that the text reminders are the most important aspect in addition to the fact that the patients feel monitored by their HCPs, which can motivate them to remember to take their medication. On the other hand, when asked about potential difficulties with the system, providers mentioned that the patch can be uncomfortable and that some patients can find it stigmatizing. Furthermore, the availability of a stable Internet connection needed to operate the system can be impossible for some patients with socioeconomic difficulties who are unable to purchase wireless Internet services. When asked if their patients had used other electronic monitors in the past, some mentioned using Wisepill© and MEMS©. They explained that the DMP would be better in measuring adherence compared to MEMS© as some patients opened the pillbox without ingesting their pills, which gave an inaccurate measure of adherence. For the Wisepill©, HCPs complained that the box was too big and there were no text message reminders.
When asked if they would recommend the DMP, HCPs said that they would recommend it to patients who have difficulties with adherence for short-term use, up to 6 months. One HCP puts it as follows:
In this study, we describe and analyze PLWH experiences and HIV HCPs’ opinions on real-time adherence monitoring with a focus on the DMP. The views of PLWH and HCPs were very similar. They only differed on the in-depth explanation of facilitators and barriers to ARV adherence, where HCPs provided more comprehensive reasons on why their patients were not adherent.
Both PLWH and HCPs agreed that DMP can be helpful in the management of ARV adherence. This was similarly reported by persons living with schizophrenia and their HCPs [
The interviews showed that PLWH had already developed self-management tools for medication-taking before using the DMP such as storing their medication at a specific location, taking their medication at the same time every day, or using alarm clocks. Despite that, PLWH were selected for this pilot study because they were having suboptimal adherence (signified by missed doses and/or detectable viral load) prior to their inclusion in the DMP pilot study. This meant that there was still a need for a tool that would further enhance their adherence. By combining self-management with immediate intervention in case of a lapse in adherence, DMP may provide greater support to patients with inadequate adherence. Some patients found this useful and could incorporate it into their daily routines. Similar experiences were reported for patients with schizophrenia and hypertension who used the DMP [
Furthermore, some PLWH reported inconvenience while using the adhesive patch. Similar feedback was reported on early versions of the patch with less than 10% of the participants reporting redness and skin itchiness [
For the DMP to function seamlessly, it needs a reliable wireless Internet connection and an electric supply to recharge the iPad/tablet battery. This is something to take into consideration when developing DMP for settings that may not have a reliable network or many power outlets, for the purpose of real-time adherence monitoring. If real-time monitoring is not required but rather timely monitoring the patch can store ingestion data for up to 8 days, so as long as there is connectivity at least once every 8 days, there should be no lost data; once the patient connects to the iPad, all data from the last 8 days will sync automatically. Some PLWH reported an inconvenience of having to be physically close to the tablet while wearing the patch to ensure adequate data transferability. Similar concerns were reported for Wisepill© [
The strength of this study is in the triangulation of sources between PLWH experiences and HCPs’ opinions, which gives a 360-degree view on a new ARV adherence measuring and monitoring technology. The weaknesses include the small number of participants, mostly male, middle age, MSM (study not generalizable with limited transferability or external validity), and the relatively short duration of using the DMP (4 weeks). However, the main trial of the study with a larger sample size (
Technology will continue to evolve to advance the ways we can measure medication adherence for research purposes and clinical practice. The DMP is a novel technology of real-time measuring and monitoring of medication adherence with advantages and potentials for improvement. Incorporating changes to the DMP based on the experiences of PLWH and providers will help improve the acceptability of such systems and make it more likely to optimally meet the patients’ needs.
Analyzing the content of the qualitative interviews from this pilot study guided introducing some changes in the main trial of the DMP that is currently being conducted. For example, using smart phones instead of tablets is now an available option. Future research aims to assess those changes in addition to assessing one’s experience with the DMP over a longer time frame.
Before beginning the audio taping, read the following:
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I will provide a description of the study. I am interested in asking your opinion, this will be helpful in the study, I will audio record the conversation. Is this Ok with you? The audio-recording will be anonymous, and your identity will only be revealed to me. Do you agree? If not I will take notes. What you share with me will be anonymously published and shared with other people, do you agree?
Name: Age: Profession: Years of experience in HIV care: Work Setting: Education: Number of patients seen per week: HIV source of infection/patient group (MSM/Drug use/Hetero): How would you describe the adherence of the patients you see? (probe: Low/moderate/high) What do you think are the barriers to the adherence? What do you think are the facilitators to adherence? Do you know of any adherence aids that can help your patients adhere to their treatment? Have you heard of the IS? What is your understanding of how it works? Do you think IS can help your patients with adherence? How? (patch, sensor, text messages) What issues have your patients been having/do you expect patients will have with IS? How would IS be different from other adherence real-time monitoring methods? Do you think IS is a long-term solution or short-term solution to adherence issues? How long do you think patients can be monitored using IS? Would you recommend IS to your patients? If yes, which patient group? (high/low/moderate adherence) and why? Would you recommend IS to other HCPs? (If no, why?) Do you know/heard about IS, what do you think the biggest problem (s) IS may be for using IS technology to monitor HIV patients’ adherence? Is there anything else you would like to add?
The data are not available publicly due to the identifying nature of the qualitative interviews.
Eric S. Daar and Honghu Liu are equal senior co-authors.
The authors declare that there are no conflicts of interest.
SK wrote the initial version of the manuscript, and all authors cooperated towards the final version. SK and LS collected the data. SK and CL analyzed the data. MIR and HL supervised the data analysis. HL provided insights into the data analysis and manuscript writing. ESD provided HIV clinical expertise.
The authors would like to thank the National Institute of Mental Health/National Institute of Health and the Swiss National Science Foundation for their support. This work was supported by the grant R01-MH110056 from the National Institute of Mental Health/National Institute of Health and grant P2GEP3_181061 from the Swiss National Science Foundation.