ART and PrEP: How Technological Advances Can Improve Adherence

With the rising number of individuals receiving HIV antiretroviral therapy (ART) and preexposure prophylaxis (PrEP), there is an increasing need for accurate and accessible methods to assess treatment adherence. To that end, guidelines published in 2016 by the World Health Organization include a call for research aimed at improving such approaches.¹

Traditional methods to measure adherence to ART and PrEP present several limitations. Self-report and pill counts may lead to overestimation of adherence, partially because these approaches are subject to social desirability bias, and thus the potential for inaccurate reports and pill dumping. Pharmacy data regarding refills do not indicate doses taken, and none of these measures specifically captures missed doses. Although electronic adherence monitors (EAMs) provide dose-to-dose data, reviews typically occur weeks or months later, when the opportunity for effective intervention may have passed.

A review published in Current Opinion describes recent technological advances in adherence measurement.² According to the authors, such advances will provide further insight into adherence behavior, as well as how to address patients who need intervention to improve their adherence. Ultimately, improving adherence will help achieve the full clinical and public health benefits of ART and PrEP.

Real-Time EAMs

Data on the use of real-time EAMs for adherence measurement were first published in 2010 and have since been used in a sizable body of research.³ This technology transmits a date and time stamp to a central server each time a medication is opened. Real-time EAMs allow for adherence monitoring between visits, which “may allow clinicians to intervene before viral rebound, in the case of antiretroviral therapy,” coauthor Lindsey E. Garrison, MPH, a project manager at the Center for Global Health at Massachusetts General Hospital in Boston, told Infectious Disease Advisor.

This method does not capture medication ingestion, and it may underestimate or overestimate adherence resulting from factors such as “pocket dosing” (taking more out than needed at 1 time) or “curiosity openings” (opening without removing medication). Although these problems are also linked to traditional EAM, discrepancies can be detected and addressed earlier with real-time EAM.

Potential issues include data transmission and battery failures, as well as network connectivity issues. Although the use of real-time EAM has been largely limited to research studies because of its high cost, more cost-effective versions are currently being developed.

Digital Medicine Systems

With digital medical systems (DMS), patients ingest a gelatin capsule containing a sensor 5 mm in diameter. When exposed to gastric acid, the sensor transmits an electrical signal to a receiver patch on the patient’s skin, which then transmits data via Bluetooth to a mobile application. The capsule may also contain the medication or may be consumed along with the medication. This method allows for precise tracking of drug ingestion, which “may be helpful in the future to establish biological efficacy in clinical trials,” according to Garrison. However, this method is vulnerable to the potential failure of any of the technological components.

DMS for patients with hypertension and schizophrenia has shown moderate acceptability.^4,5 Although studies are presently investigating the use of DMS for ART and PrEP, there are no published data currently available pertaining to this use, and no cost data are available on DMS.

Short Message Service

Short message service (SMS), commonly known as text messaging, can be used to send reminders or clinical information, as well as to receive self-reported information on adherence and associated behaviors. This information from patients can be used to assess whether they are using PrEP optimally for protection against HIV. Recent studies have demonstrated high rates of feasibility and acceptability of SMS for monitoring PrEP adherence.^6,7

With the majority of the global population now using cell phones, SMS offers a widely available, relatively inexpensive method of monitoring adherence. However, issues such as privacy concerns, literacy, and general challenges associate with self-report methods may limit the effectiveness of this approach.^8,9

Pharmacokinetic Measures

These techniques “provide direct assessment of drug ingestion in varying compartments and tissues, including plasma, red blood cells…collected on dried blood spots…hair, and peripheral blood mononuclear cells,” as described in the paper. Dried blood spots and hair, in particular, are easy to store and process, and they offer a high level of biosafety.

There are potential barriers regarding cost, feasibility, and acceptability. For example, all such methods require the use of specialized laboratory equipment to assess results, and some methods require a skilled technician. Point-of-care approaches and alternate assessment methods that are currently being investigated may offer lower-cost, more accessible options.

Summary

Although each of these approaches has advantages and limitations, confidence in adherence estimates “is higher when multiple measures indicate similar results and particularly when one or more measures is objective,” the authors wrote. In addition, they noted that with any approach, the Hawthorne effect should be considered. The Hawthorne effect describes a behavior change that occurs as a result of the behavior being monitored, and it has been observed in studies of ART and PrEP in which increased monitoring was associated with increased adherence.^10,11

Further research in this area “should focus on combining objective and subjective measures of adherence. For instance, using dried blood spots, real-time electronic adherence monitoring, and SMS surveys together can help validate the individual measures,” said Ms. Garrison. “Future developments should focus on providing a seamless experience for the end user to increase feasibility and acceptability.”

 

 

References

1. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV Infection, 2nd edition. Recommendations for a Public Health Approach. Geneva: World Health Organization; 2016.
2. Garrison LE, Haberer JE. Technological methods to measure adherence to antiretroviral therapy and preexposure prophylaxis. Curr Opin HIV AIDS. doi:10.1097/COH.0000000000000393 
3. Haberer JE, Kahane J, Kigozi I, et al. Real-time adherence monitoring for HIV antiretroviral therapy. AIDS Behav. 2010;14(6):1340-1346. doi:10.1007/s10461-010-9799-4
4. Peters-Strickland T, Pestreich L, Hatch A, et al. Usability of a novel digital medicine system in adults with schizophrenia treated with sensor-embedded tablets of aripiprazole. Neuropsychiatr Dis Treat. 2016;12:2587-2594. doi:10.2147/NDT.S116029
5. DiCarlo LA, Weinstein RL, Morimoto CB, et al. Patient-centered home care using digital medicine and telemetric data for hypertension: feasibility and acceptability of objective ambulatory assessment. J Clin Hypertens (Greenwich). 2016;18(9):901-906. doi:10.1111/jch.12787
6. Curran K, Mugo NR, Kurth A, et al. Daily short message service surveys to measure sexual behavior and pre-exposure prophylaxis use among Kenyan men and women. AIDS Behav. 2013;17(9):2977-2985. doi:10.1007/s10461-013-0510-4
7. Haberer JE, Ngure K, Muwonge TR, et al. Prevention-effective adherence per SMS surveys within a demonstration project of PrEP among HIV serodiscordant couples in East Africa. International Conference on HIV Treatment and Prevention Adherence. Fort Lauderdale, Florida: Partners Mobile Adherence to PrEP Team; 2016.
8. Sabin LL, Bachman DeSilva M, Gill CJ, et al. Improving adherence to antiretroviral therapy with triggered real-time text message reminders: The China Adherence Through Technology Study. J Acquir Immune Defic Syndr. 2015;69(5):551-559. doi:10.1097/QAI.0000000000000651
9. Haberer JE, Musiimenta A, Atukunda EC, et al. Short message service (SMS) reminders plus real-time adherence monitoring improve adherence to antiretroviral therapy in rural Uganda. AIDS. 2016;30(8):1295-1300. doi:10.1097/QAD.0000000000001021
10. Haberer JE, Musinguzi N, Tsai AC, et al. Real-time electronic adherence monitoring plus follow-up improves adherence compared with standard electronic adherence monitoring. AIDS. 2017;31(1):169-171. doi:10.1097/QAD.0000000000001310
11. Musinguzi N, Muganzi CD, Boum Y 2^nd, et al; Partners PrEP Ancillary Adherence Study Team. Comparison of subjective and objective adherence measures for preexposure prophylaxis against HIV infection among serodiscordant couples in East Africa. AIDS. 2016;30(7):1121-1129. doi:10.1097/QAD.0000000000001024