In Canada, approximately 75,500 people are living with human immunodeficiency virus (HIV), 16,800 of whom are women [1]. Combination antiretroviral therapy (cART) has led to enormous improvements in health and survival of HIV-positive individuals [2]. Moreover, by decreasing the amount of virus circulating in the plasma (viral load [VL]), cART offers the possibility of treatment as prevention by minimizing viral transmission [3,4]. Despite the well-established benefits of cART, nonadherence to medications, delayed initiation of therapy, and poor follow-up are ongoing limitations of effective HIV management leading to multidrug resistance, progression to acquired immune deficiency syndrome (AIDS), transmission to others, and mortality [2,5-7].

Engagement in longitudinal HIV care is an ongoing challenge, with studies from the United States showing long-term retention in care ranging from 37% to 65% [8-11]. Retention in care is particularly important on a public health scale because those individuals not retained in care have been estimated to account for twice as many HIV transmissions as nondiagnosed individuals [11]. In British Columbia, Canada, there is emerging evidence that cART adherence among women is lagging behind that of men (59% vs 68%, respectively) [12]. A variety of factors have been shown to decrease care retention and cART adherence in women, including intimate partner violence, medication side effects, role as care provider, and gender-specific stigma [13-19]. Other risk factors associated with poor adherence in both men and women include substance abuse, recent incarceration, psychiatric conditions, advanced HIV, and lack of social or housing supports [8,20-25]. Previous peer mentoring and behavioral interventions tested in these populations have failed to show objective improvements in HIV care [26-28]. For an illness that now has beneficial long-term treatment available, effective adherence strategies for difficult-to-engage populations will be of paramount importance from an individual and public health standpoint.

Mobile health (mHealth), the use of mobile phone technology to deliver health care, is an emerging area of disease management that can assist in patient adherence to prolonged chronic treatment regimens and monitoring of care [29-31]. Short message service (SMS) text messaging is particularly appealing as a mHealth intervention because it makes use of standard services offered by cellular providers, requires minimal additional infrastructure, and is user-friendly, ubiquitous, and flexible [29,30,32]. In a landmark randomized controlled trial, Lester et al conducted a mHealth intervention (WelTel Kenya1) whereby providing a bidirectional, weekly text-messaging intervention for one year significantly improved cART adherence and VL suppression compared with controls in an HIV-positive Kenyan population initiating cART [16]. Several other SMS text-message interventions have been developed and implemented in HIV care with promising results; however, WelTel remains the approach validated in the largest setting to date [33-35]. In addition, reviews and a meta-analysis have assessed available evidence to confirm that SMS text-message interventions can improve parameters of HIV care, especially cART adherence [17,36-38]. Despite this emerging evidence, there remains a lack of focus on vulnerable populations less likely to access care and a paucity of data focused on female populations [39-42]. Our goal in this study was to assess whether the standardized WelTel intervention applied to a vulnerable, predominantly female population improved cART adherence and VL.

This study showed that a cohort of difficult-to-engage, vulnerable individuals living with HIV showed evidence of improved measures of HIV care (VL, cART adherence) when exposed to a weekly bidirectional text-messaging intervention. The study is unique in that participants were provided with mobile phones, allowing for increased engagement of marginalized populations that would otherwise be difficult to access. This intervention could potentially bring substantial health benefits to vulnerable populations in an era in which HIV care is largely limited by medication adherence.

The population demographic was a marginalized, predominantly female cohort with markers of poor HIV engagement. Participants came from a diversity of backgrounds and exhibited the wide range of vulnerabilities and barriers to care that could be encountered in any typical North American urban setting (Table 1; [24,40,45-48]). Vulnerabilities common in our population, including mental illness (48%), active substance use (28%), and unstable housing (17%), have been previously associated with poor cART adherence [24,45-50]. Cell phone ownership in this cohort was lower than average among Canadians (54% vs 82%), further confirming the inaccessible nature of this vulnerable study group [51,52]. By including a majority of women, we propose an adherence strategy applicable for the growing proportion of women living with HIV, a subpopulation that has been minimally studied and has characteristically poor cART adherence [13-15].

Our study demonstrated that effective introduction of the WelTel intervention decreased VL within our cohort. VL in our population was initially 1098 copies/mL, more than double the estimated mean of less than 500 copies/mL in British Columbia [53]. This dropped significantly following introduction of the WelTel intervention to a level that was on par with the provincial average by study end (439 copies/mL, P=.004; Table 2). Effective cART therapy is known to reduce viral replication [2]. Therefore, the observed VL reduction is likely a consequence of increased cART adherence (OR 1.14, IQR 1.10-1.18, P<.001) and minimizing treatment interruption during the WelTel intervention; we expect this relates to prompt recognition of problems and close connection with care. Due to the nature of studying a high-risk group, there is a risk of exaggerating treatment effects due to anticipated regression to the mean. However, additional analysis suggested that those who regularly used the service (ie, repliers) trended toward greater benefit to VL (Figure 4; P=.07). This argues that the improved parameters of HIV care may be due to exposure to the WelTel intervention rather than regression to the mean.

WelTel likely mitigated common barriers to cART adherence by (1) serving as a user-friendly, patient-directed connection tool with the care team, (2) connecting patients in an ongoing fashion with a support network to reduce the effects of isolation and stigma, and (3) aiding health care providers in identifying and resolving problems (both medical and related to the social determinants of health) as they arose, thereby preventing crises. Although the odds of adhering to cART was significantly improved during the intervention (OR 1.14, IQR 1.10-1.18, P<.001), the rate of adherence showed only modest improvement (60.3% vs 62.2%, Table 2). We expect that this difference appears small for a variety of reasons, including inaccuracies in self-reported adherence, failure to report treatment interruption, and a large variance in adherence rates. The strategy of early recognition and mitigation of problems has been shown to prevent treatment interruption in other settings as well, such as directly observed treatment of tuberculosis [54]. WelTel appears to improve patient-provider relationships by opening a channel of communication through which both medical concerns and those related to the social determinants of health may be addressed [18,44]. We expect that as these relationships improve and so, in turn, will medication adherence and eventually VL. Taken together, these results suggest that WelTel may be an effective patient-oriented tool to support and improve care in vulnerable HIV-positive populations.

The secondary outcome showing decreased clinic appointment attendance during our intervention year was an unexpected finding (Table 2). In other studies, participant fatigue has occurred with frequent or lengthy messaging interventions [34]. However, our observed consistency in texting response rates suggests that user fatigue does not explain our lower clinic attendance (Figure 3). Instead, we postulate that WelTel addressed common problems that would otherwise be resolved at clinic appointments to the point where participants had a decreased need for clinical appointments [18,29]. Despite having lower clinic attendance after the WelTel intervention, several other markers of health status, such as VL, emergency visits, and hospitalization rates, were the same or improved with the text-messaging intervention (Table 2). A previous hypertension study found that using two-way SMS text-message feedback and telephone consultation as a guide to plan ambulatory care management allowed for improved blood pressure management [55]. This raises the possibility that an effective two-way text-message intervention could be used to help guide HIV ambulatory follow-up frequency, in some cases safely decreasing appointment frequency. Finally, the text-messaging platform could be used to send reminders for upcoming appointments, a technique that has successfully improved clinic attendance in similar studies [34,39,56].

The text-messaging response rate was consistent throughout the study without any tapering trend (Figure 3). Previous studies involving patient participant feedback examined the optimal length and frequency of text messaging and found the best approach to maximize responses was a short weekly SMS text message, as opposed to daily texts or longer messaging interventions [33,34,39]. Our study supports this messaging strategy by showing consistent response rates after a full year of weekly text messages. The consistency in response rates that we observed also suggests that participants continue to make use of the intervention after one year, highlighting its feasibility in promoting long-term patient engagement. Previous studies have shown that mHealth interventions continue to have effect up to 18 months after introduction, but the optimal duration beyond this has not yet been studied nor have we seen whether there is a lasting effect if the intervention is withdrawn [16]. As WelTel moves toward broadening its application, future studies investigating the optimal duration of text-messaging interventions and the durability of its effect would help to guide implementation of this tool. Finally, through our analysis of participant engagement, we observed that some of those participants most poised to benefit from the intervention (ie, less adherent with cART) had poor uptake of the intervention in general. This may be because certain characteristics that result in poor adherence in HIV care also contribute to poor engagement with our intervention. Moving forward, it would be of interest to further delineate participant characteristics to anticipate who may maximally benefit from the intervention and for whom the resources will not be effectively allocated.

This study is a repeated measures study rather than a randomized controlled trial; therefore, we are only able to infer association not causation. WelTel had strong evidence of benefit in previous studies and, as such, our study was designed as a cohort study to offer maximal resources to all individuals in a high-risk population rather than random allocation [16-18]. Our study is limited by its sample size, predominantly female composition, and high-risk population studied, and it is therefore not generalizable to all populations. Medication adherence, one of our secondary outcomes, is a notoriously difficult parameter to study and patient self-reports are susceptible to recall bias and reporting inaccuracies. To mitigate this, we included pharmacy refill data in our assessment of number of doses taken, with the lower value being recorded as the correct one. Despite this, our method may still overestimate the number of pills actually ingested. Another limitation was that a large proportion of our cohort (47%) received a cell phone from us during the study, and we cannot control for all effects of cell phone ownership alone. Owning a mobile phone may impact several social determinants of health by impacting relationships, mobility, mental health, and self-perception [57,58]. Changes in these parameters may have gone on to positively influence outcomes associated with HIV care. Finally, multiple factors contribute to a patient’s engagement in care, decision to initiate cART, and readiness to adhere to medication. Complex issues such as mental health and substance use cannot be solved by text messaging alone. However, it is our hope that this technology may act as a facilitator to establish a meaningful connection to care so that our most vulnerable patients may be better able to utilize and engage in the services available to them.

This study found that a simple and easily implemented mHealth intervention may significantly improve HIV care in vulnerable populations, a finding that holds great potential for real world application. Moving forward, further identification of subgroups poised to benefit most from WelTel will be important, particularly if the intervention includes the provision of a cell phone and phone plan. Finally, a cost analysis would shed light on the feasibility of introducing WelTel in a larger scale to targeted populations. We anticipate that the cost of the intervention would be mitigated by the cost-savings benefit of reduced HIV transmission and decreased use of health care resources associated with effective HIV care [2,59]. Taken as a whole, this study is pivotal in proposing an adherence strategy for at-risk HIV populations that we hope can be applied in a broad clinical context.