Mobile phone-enabled adherence in HIV/AIDS
Authors: Edward J Mills, Richard T Lester
Journal: The Lancet Digital Health (2019)

The HIV/AIDS epidemic in low-income countries has improved thanks to several technological and anthropological advances in health care.1Ford N Calmy A Mills EJ The first decade of antiretroviral therapy in Africa.Global Health. 2011; 7: 33Crossref PubMed Scopus (59) Google Scholar The introduction of laboratory equipment to initially monitor CD4 T-helper cells in 2004 was a technological breakthrough in low-resource settings because many researchers thought that the expensive laboratory infrastructure could not be consistently maintained. Training and access to testing equipment led to widespread uptake. Similarly, the progressive introduction of viral load and resistance testing has shown that even the most complex technological requirements can, with time, be rolled out at a large scale in low-resource settings.2Ford N Vitoria M Doherty M Providing antiretroviral therapy to all who are HIV positive: the clinical, public health and programmatic benefits of Treat All.J Int AIDS Soc. 2018; 21: e25078Crossref Scopus (15) Google Scholar The rapid uptake of mobile phones in low-income settings displays an anthropological advancement, in which the use of mobile phones has surpassed the development of infrastructure for landlines that does not exist. In the early 2000s, mobile phones in low-income settings became ubiquitous for managing banking, education, and health care.3In much of sub-Saharan Africa, mobile phones are more common than access to electricity.The Economist. Nov 8, 2017; https://www.economist.com/graphic-detail/2017/11/08/in-much-of-sub-saharan-africa-mobile-phones-are-more-common-than-access-to-electricityDate accessed: April 4, 2019Google Scholar Mobile devices quickly became a norm for interacting with patients in HIV/AIDS clinics, often via short message service (SMS) and in 2010 the first randomised clinical trial4Lester RT Ritvo P Mills EJ et al.Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial.Lancet. 2010; 376: 1838-1845Summary Full Text Full Text PDF PubMed Scopus (915) Google Scholar of cellular devices for monitoring adherence to first-line antiretroviral therapy (ART) in patients living with HIV was published, displaying a modest benefit on self-reported adherence and viral suppression. In this issue of The Lancet Digital Health, Robert Gross and colleagues5Gross R Ritz J Hughes MD et al.Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomised controlled trial.Lancet Digital Health. 2019; 1: e26-e34Summary Full Text Full Text PDF Scopus (17) Google Scholar present the first randomised controlled trial in second-line treatment and fill an important gap in knowledge about the use of SMS in the HIV/AIDS epidemic. Among the many challenges of monitoring adherence to ART in any setting is how adherence is measured. Self-reported adherence (usually based on 3-day recall), pill counts, and electronic monitoring of medication package opening have all been used to assess adherence but are surrogate outcomes to the medical intention of treatment: to suppress the virus. In the figure, the top panel shows the outcomes of the previously reported SMS trials that measure adherence using these surrogate outcomes. The bottom panel shows the results of the only three trials that have used viral load as an outcome. The uncertainty in interpreting these inconsistent trials was previously ascribed to low statistical power to detect effects because most patients living with HIV in these settings have high adherence rates, thus, we would expect high reported adherence and viral suppression. The study by Gross and colleagues5Gross R Ritz J Hughes MD et al.Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomised controlled trial.Lancet Digital Health. 2019; 1: e26-e34Summary Full Text Full Text PDF Scopus (17) Google Scholar is a major contribution in this context because it is the first randomised trial to enrol a population with shown ART challenges in terms of resistance or previous treatment failures and thus is likely to be adequately powered. Although this multicountry study had a small heterogenous population exposed to ART, the findings are statistically definitive that this specific intervention offered no detectable benefit on viral load suppression. We confirmed the findings using Bayesian simulations and found that even with additional thousands of patients, the results would not change (appendix). The findings of the present study,5Gross R Ritz J Hughes MD et al.Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomised controlled trial.Lancet Digital Health. 2019; 1: e26-e34Summary Full Text Full Text PDF Scopus (17) Google Scholar that the SMS intervention did not detect a useful treatment effect in the primary outcome, should be considered in terms of whether SMS in general should be used as an adherence support tool or not. The study was well designed and well done. Previous randomised controlled trials investigating SMS interventions have varied slightly in how the SMS is delivered, whether that be one-way or two-way texts (response monitored or not), once daily versus once weekly texts, and the construction of the texts (health questions versus a simple colloquial question–eg, "How are you?"). The mixed findings on viral suppression versus virological failure, combined with alterations in the intervention from previous SMS-based mobile phone interventions in the published literature, mean it is still unclear whether SMS should be advocated for patients. Although the approach requiring patients to "flashback" to indicate they've taken their medications and getting contacted after missing three replies in a row is justified by the authors on cost grounds, the acceptability of this approach for patients is unknown.7Ronen K Unger JA Drake AL et al.SMS messaging to improve ART adherence: perspectives of pregnant HIV-infected women in Kenya on HIV-related message content.AIDS Care. 2018; 30: 500-505Crossref PubMed Scopus (30) Google Scholar Previous studies simply asked patients to indicate when they had issues that would then be followed up directly by health staff, a proposed mechanism for positive adherence behaviour change.8Chiang N Guo M Amico KR Atkins L Lester RT Interactive two-way mHealth interventions for improving medication adherence: an evaluation using the behaviour change wheel framework.JMIR mHealth uHealth. 2018; 6: e87Crossref PubMed Scopus (29) Google Scholar The intensity of messaging, once daily versus once weekly, is poorly understood but less frequent messaging might be preferable.9Pop-Eleches C Thirumurthy H Habyarimana JP et al.Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders.AIDS. 2011; 25: 825-834Crossref PubMed Scopus (677) Google Scholar Amid the surge of technological tools now being introduced in health care, from mobile phone-based technologies to different app interfaces, the speed with which their uptake occurs will make measurement of their utility by traditional methods difficult. Just as cell phones have overtaken landlines in many low-resource settings, health systems will need to continually adapt to ensure the primary goal of improving patient care in an equitable way is realised. SMS is still the most common communication technology in the world today; however, large shifts could rapidly occur again and might have already started—eg, the use of communication apps such as WhatsApp and Snapchat. Advancement might be less about the specific technology modalities themselves and more about how they are dynamically used to change the way care is delivered and how they motivate positive changes in health behaviours, which should be reflected in new methods of assessment. For instance, adaptive assessments that enable evolution of the intervention being investigated, and inclusion or exclusion of emerging technologies (and those decreasing in popularity), need to be considered. The problem of non-adherence among people at the highest proven risk remains to be solved, and innovations are needed in both the medical and evaluative approaches. RTL reports grants from WelTel, outside of the submitted work, and is a co-owner of WelTel Inc. RTL is also a recipient of several grants via peer-reviewed granting entities (eg, Canadian Institutes for Health Research) to assess the role of mobile health initiatives for improved health outcomes, including adherence. EJM has no competing interests. Download .pdf (.18 MB) Help with pdf files Supplementary appendix Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomised controlled trialTwo-way MPI did not significantly improve week 48 suppression, but it did modestly affect virological failure. People failing second-line ART might not achieve benefits from phone-based triggers or enhanced adherence support (or both). More effective strategies are needed. Full-Text PDF Open Access