Introduction

Antiretroviral therapy (ART) is a powerful tool to prevent illness and death for the 35 million people living with HIV globally, as well as to avert new infections [1]. However, availability of treatment alone is insufficient to end the HIV epidemic. Globally, 22 million people, or three out of five people living with HIV, are unable to access treatment [1, 2]. The new UNAIDS 90-90-90 goals aim to end the epidemic in 2030, with 90 % of all people living with HIV knowing their HIV status, 90 % of all those diagnosed with HIV receiving sustained ART, and 90 % of all people receiving ART virally suppressed by 2020 [2].

Digital technology interventions are emerging as one approach to support lifelong engagement in the HIV care continuum: linkage and retention in care, ART initiation and adherence, and viral suppression (Fig. 1) [3]. Approximately 25 million people living with HIV are in sub-Saharan Africa, accounting for nearly 71 % of all people living with HIV globally [1]. With significant proportions of people living with HIV in resource-limited settings, interventions that use technology to respond to the pandemic must be widely accessible or scalable in these contexts. In addition, specialized interventions are required for key populations facing significant barriers to treatment—those who are most at risk of becoming the “10-10-10” who are unable to engage in care.

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HIV continuum of care

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Mobile phones have had enormous reach in resource-limited settings, providing real potential for low-cost adoption to support engagement in HIV care. Accordingly, the majority of studies on HIV engagement technologies have used mobile devices (mHealth), often capitalizing on widely used and available text messaging, or short-message-service (SMS). Point-of-care (POC) diagnostics and other lower cost laboratory testing and monitoring services, together with wireless electronic informatics, provide additional opportunities to improve engagement in HIV care. Furthermore, a smaller but significant portion of the epidemic affects people with access to technologies such as broadband internet, smartphones, and/or social media; thus many innovations are using “Web 2.0” and other advancing technologies.

This review provides an update on evidence for digital technology interventions for engagement in HIV care after diagnosis. Digital technologies examined include mHealth, eHealth, and telehealth, which are not mutually exclusive (Table 1).

Table 1 Types of digital technology interventions for engagement in HIV care
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Methods

We searched Google Scholar and PubMed for articles published between 01/01/2014 and 05/31/2015 using the keywords HIV, smartphone, telemedicine, ICT, eHealth, and mHealth. Additional articles were identified through searches of technology-focused health journals for HIV-related articles. Articles published in peer-reviewed journals were included if they discussed digital technology interventions in the context of the HIV care continuum. Relevant articles included primary research (qualitative and quantitative), reviews, and commentaries. Conference abstracts, theses, grey literature, protocols, and book chapters were excluded. Articles focused on HIV prevention and HIV-related activism were also excluded. Articles were evaluated, summarized, and synthesized jointly by all authors.

Results

We identified 15 reviews that presented evidence of technology interventions for engagement in HIV care (Table 2). In addition, our search revealed 18 peer-reviewed articles describing new intervention studies (Table 3). Finally, 11 articles described technology use among key populations and feasibility/acceptability of technology interventions for engagement in HIV care (Table 4). Technologies evaluated ranged from simple text messaging via mobile phones to complex smartphone, internet-based interactive platforms, or informatics. Several studies investigated the use of SMS for appointment and medication reminders, while others examined bi-directional SMS programs that supported communication between patients and healthcare providers. Fewer studies investigated other types of healthcare technologies, for example, advances in POC laboratory testing and its role in patient engagement in the care continuum.

Table 2 Recent reviews that include studies of digital technologies for engagement in HIV care
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Table 3 New evidence of digital technologies for engagement in HIV care
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Table 4 Emerging research on the feasibility of digital technologies for engagement in HIV care
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Review of Reviews

Linkage to and Retention in Care

Brennan et al. identified five randomized controlled trials (RCTs), two on linkage to care and three on retention in care [4] (Table 2). Only one included trial evaluated a technology intervention: telephone reminders decreased missed appointments from 11.4 to 7.8 % in primary care, and suggested an effect but was underpowered for a subgroup of HIV patients [4]. Overall, this review suggests significant opportunity for research into technology interventions to support linkage to and retention in HIV care.

One systematic review of 24 completed studies and 15 ongoing trials identified by Govindasamy et al. investigated interventions to improve linkage to care, retention in care, and ART initiation in low-income settings observed that the highest quality studies included those that tested POC CD4 testing, patient navigation, rapid ART initiation, and mHealth programs [5]. The rest were limited as they were observational with unclear risk of bias. The authors call for further high-quality studies with key populations, informed by existing evidence on barriers to care [5].

Muessig et al. identified 23 intervention and 32 pre-trial funded project publications assessing technologies that require services beyond text messaging, including eHealth, mHealth, and Web 2.0 social media interventions spanning HIV prevention and the continuum of care [6••]. Their findings suggest that significant gaps remain around linkage to care, retention in care, and ART initiation [6••].

Finally, Robustillo Cortes et al. conducted a review of smartphone apps related to HIV/AIDS and assessed each for quality and main strengths and weaknesses [7]. Of 41 apps developed before 2012, only 1 (Practice HIV) was of exceptional quality, and 50 % did not achieve minimum quality standards. Overall, quality of existing HIV-related smartphone apps is generally low.

ART Adherence

In this issue, interventions to support adherence have been comprehensively reviewed by Amico [8]. Briefly, we identified several reviews published on interventions to improve ART adherence with the use of technologies. These include a network meta-analysis [9••], a rapid systematic review [10], four meta-analyses [11, 12••, 13, 14], a descriptive narrative evaluation [15], and two systematic reviews [16, 17]. Overall, these reviews concluded that mHealth interventions, and those that used SMS in particular, improved adherence [9, 11, 12••, 16]. Taken together, the evidence supported weekly (versus daily) contact with patients [9, 11], and personalized, two-way interaction [11, 12]. The greater adherence benefit found with two-way text messaging may be explained by opportunity for social contact for otherwise isolated patients and improved communication between patients and care providers [12]. Despite the consistency of the findings, some authors called for rigorous, longer-term studies to gauge the efficacy of mHealth interventions on adherence over time [16].

Summary

Results from reviews demonstrate considerable evidence supporting mHealth for ART adherence. Several reviews revealed important distinctions in what works and what does not. Overall, programs that enhance communication between healthcare providers and patients have the greatest success in improving treatment adherence, and the evidence for text messaging is more developed than for more complex technologies. Significant gaps remain in development and testing of technology interventions for linkage, retention, and ART initiation.

Of note, there was substantial overlap in the HIV-related technology studies included in these reviews. Overall, study quality is an issue and bias remains a risk in interpreting the evidence. In a review seeking high-quality studies of interventions enhancing adherence to ART, only 10 of the 49 improved both ART adherence and a clinical outcome, and many had a high risk of bias [17]. Similarly, in Anglada-Martinez et al.’s review, only one trial [18] was considered to have low risk of bias [13] using the Cochrane Collaboration tool to assess risk of bias. Future assessments of ART adherence interventions should consider measuring clinical outcomes to determine the intervention’s effect on patient health and investigators should ensure study designs minimize risk of bias. Furthermore, the HIV continuum of care is lifelong; subsequently, longer-term trials and cohorts are required to assess real-world effectiveness over time.

Although some reviews of engagement in care interventions focused on key populations, including young people [19] and African-American women [20], these reviews did not identify any technology interventions for these particular groups. There is a paucity of current research on tailored technological interventions to support key populations to engage in HIV care.

Recent Primary Studies

Linkage to Care

HIV testing often occurs at sites that do not automatically link into care, such as community voluntary counseling and testing sites and home-based testing. The period immediately after testing HIV-positive is a critical time. However, no studies were identified that evaluated technology interventions to improve linkage to care, suggesting that this is a key area requiring innovation (Table 3).

Retention in Care

Successful HIV treatment depends on sustained, lifelong engagement in care. As a result, researchers are increasingly interested in interventions that support people living with HIV to remain engaged over time. Nine articles measured the effect of a variety of technology interventions on retention in care [21–29]. mHealth appears to be the predominant mode for delivery as all but two of the retention in care studies tested mHealth interventions or an mHealth hybrid program.

A small RCT (n = 52) among adults attending an HIV clinic in Durham, North Carolina found no difference in clinic attendance among those who received SMS appointment reminders, compared to controls (72 % versus 81 %, p = 0.42) [21]. However, this study may be limited by small sample size and because 24 % of intervention participants did not receive reminders because of phone disconnection [21]. The authors concluded that an effect was not observed due to “logistical challenges” in implementing reminders [21].

Oluoch et al. used a retrospective population-level study to determine changes in quality of pre-ART care before and after introduction of an eMR system in 17 rural HIV clinics in Kenya [22]. They found that among 18,523 patients receiving pre-ART care, those who received care using an eMR (n = 3047) were significantly more likely to receive a CD4 test (OR 1.59, 95 % CI 1.49–1.69) [22].

Retention for HIV-Related Maternal and Child Health

Evaluating technology interventions for retention in care for prevention of mother-to-child transmission (PMTCT) is an important area of research as three out of ten pregnant women living with HIV do not receive ART, and one child becomes infected with HIV every two minutes [1]. Furthermore, only 24 % of 3.2 million children living with HIV globally are currently receiving HIV treatment [1]. Without treatment, approximately one third of children living with HIV die by their first birthday and half die by their second [1]. Three recent studies in sub-Saharan Africa used technology to improve retention in care for infants and caregivers.

An RCT of 242 carers of children infected with/exposed to HIV in Cameroon found that reminders sent via concomitant SMS and mobile phone call were most effective in improving appointment attendance (OR 7.5, 95 % CI 2.9–19.0; p < 0.0001), although text messaging alone was more cost-effective (OR 2.9, 95 % CI 1.3–6.3; p = 0.012) [23••].

Fifty HIV-positive pregnant women attending a clinic in Johannesburg, South Africa participated in a pilot study to test the potential of mobile phone case management to improve infant HIV testing and maternal retention in care [24]. Outcomes among pilot study participants were compared to 50 similar women attending the clinic in the period immediately preceding the intervention [24]. There were no differences in maternal retention in care between the two groups; however, infants were more likely to be tested for HIV in the pilot study group [24]. Furthermore, intervention participants reported that the emotional support, information, and reminders were helpful to them [24].

Mother-infant pairs attending two hospitals in Kenya were enrolled in an observational pilot study before (n = 320) and during implementation (n = 523) of the HIV infant tracking system (HITSystem), a hybrid Internet/SMS program to improve the flow of laboratory testing and alert mothers when results are ready [25]. Researchers observed an increase in the proportion of HIV-exposed infants retained in care as well as those initiated on ART during the intervention [25].

Clinical and Laboratory Interventions to Improve Retention in Care

With a worldwide push to build laboratory capacity toward global treatment goals, digital technology interventions to improve laboratory testing processes and notification are relevant [2]. Furthermore, point-of-care (POC) diagnostics are a developing area essential for preventing patient attrition from HIV care and ensuring opportunistic infections are promptly identified and addressed [26].

In Swaziland, six clinics were provided with mobile phones equipped to receive patient lab test results via SMS. A qualitative study observed improved turn-around time as compared to the standard paper report delivery system [27].

Siedner et al.’s trial to evaluate the efficacy of an SMS application to notify people living with HIV (n = 385) of laboratory results in rural Uganda found that those with concerning results and higher literacy were more likely return to clinic (OR 3.81, 95 % CI 1.61–9.03, p = 0.002) [28•]. Literacy at enrollment was strongly associated with response to SMS notifications [28•].

Jirawison et al. tested telemedicine to improve POC screening of a common HIV-related opportunistic infection, Cytomegalovirus (CMV) retinitis, among 103 patients attending an HIV clinic in Thailand [29]. Compared to gold standard diagnostic tests, the digital screening program was less sensitive but may present an opportunity to more rapidly identify severe retinitis that poses an immediate threat to vision [29].

In summary, recent evidence on technology interventions for retention in HIV care, including those for PMTCT and laboratory processes and notification, is promising. However, several studies were small pilot studies or used observational and qualitative study designs. Larger, longer-term RCTs are needed. Furthermore, a majority of studies were set in sub-Saharan Africa; as barriers to retention in care may be quite different in other contexts, additional research is required.

Antiretroviral Initiation and Adherence

Despite recommendations for earlier initiation of ART, time to initiation and adherence remain a challenge. Ten papers published since January 2014 provide new evidence on technology interventions for ART initiation and adherence.

Dryden-Peterson et al. conducted a stepped-wedge cluster RCT to test the effect of an automated SMS platform to relay CD4 results for 366 pregnant women with HIV attending 20 antenatal clinics in Botswana [30••]. Time-to-delivery of CD4 results from lab to clinic was reduced from 16 to 6 days (p < 0.001) [30••]. However, ART initiation was still low among intervention participants (36.4 %) and not significantly different from the control group (OR 1.06, 95 % CI 0.53–2.13, p = 0.87) [30••].

Oluoch et al. conducted a second study, this time to determine efficacy of an eMR on ART initiation among 7298 patients from 17 Kenyan clinics [31]. Patients in the eMR group had a 22 % increase in odds of initiating ART, compared to patients in a paper-based system (OR 1.22, 95 % CI 1.12–1.33) [31]. However, one limitation in eMR deployment in many clinical settings in Africa is that data is often not entered or accessible real-time during patient visits, and instead functions as records for monitoring and evaluation rather than enhanced clinical care.

eMRs may also present an opportunity for patient engagement by making personal health information available online. A cross-sectional study examined My HealtheVet, an electronic personal health record (ePHR), to engage veterans living with HIV in San Francisco, USA. Greater patient activation and satisfaction, viral suppression, and awareness of current health status were observed among those using ePHR (n = 20) compared to controls (n = 20) [32]. No differences between groups were observed in terms of CD4 count, provider satisfaction, healthcare empowerment score, or ART adherence [32]. In addition, Côté et al. in Montreal, Canada tested a virtual nursing intervention for HIV self-management (VIH-TAVIE) using a quasi-experimental design (n = 179); however, adherence among patients receiving online follow-up was no different than among controls [33].

Perera et al. evaluated a smartphone application to send graphical representations of plasma ART concentrations and viral load using an RCT in Auckland, New Zealand (n = 28). Intervention participants had lower viral load (p = 0.023) and improved adherence (p = 0.03) at 3 months [34].

In an RCT among 631 ART-naïve patients in rural South India, Shet et al. found no difference in time to virological failure (HR 0.98, 95 % CI 0.67–1.47, p = 0.95) or adherence (IRR 1.24, 95 % CI 0.93–1.65) between participants receiving customized, interactive, automated voice reminders, plus a weekly pictorial message, compared to participants receiving standard of care [35].

Swendeman et al. conducted a mixed-method pilot study (n = 46) of an automated twice-daily interactive voice response intervention to support ART adherence in Kolkata, India [36]. A pre-post design showed significant increases in self-reported adherence at 1 month (p = 0.05) and a longer-term randomized trial is now underway [36].

Citing mobile phones as a convenient, culturally relevant means of communicating with youth, Belzer et al. performed a six-month RCT involving 37 young people living with HIV 15–24 in five US cities. Intervention participants (n = 19), who received daily mobile phone calls to confirm medication adherence plus problem solving support, reported greater adherence (p = 0.007) and reduced viral load (p = 0.043), compared to controls [37]. However, findings should be considered carefully as seven of 19 intervention participants were removed from the study after missing more than 20 % of calls, going off medication for ≥14 consecutive days, or missing calls for 10 consecutive days [37]. This punitive approach may exclude the very participants struggling the most to engage in care.

In a 30-day RCT involving 50 people living with HIV with coexisting bipolar disorder in San Diego, USA, Moore et al. found that those receiving individualized two-way, medication SMS reminders (iTAB) had similar adherence to controls for both psychotropic and antiretroviral medications, but took medication closer to intended dosing time (p = 0.02) [38•].

Young et al. compared the efficacy of subspecialty HIV care via telemedicine to on-site management by a correctional physician in an Illinois, USA prison [39]. The observational study (n = 687) demonstrated improved odds of virologic suppression in the telemedicine group despite the same number of visits (OR 7.0, 95 % CI 5.1–9.8, p < 0.001) [39]. Despite the relatively low quality of evidence provided by this study, it is an important contribution [40, 41]. Globally, 10 million people are incarcerated at any point in time and 30 million spend time in prison each year [1]. In addition, people with HIV are overrepresented in prisons due to criminalization of many HIV risk behaviors, including same-sex sex, intravenous drug use, and sex work. Prisoners are at risk of HIV treatment interruption and face considerable unmet healthcare needs [1]. As a result, Young et al.’s study is a critical starting point to understand how technology interventions can support engagement in HIV care for prisoners and ensure continuity of care upon release.

Emerging Research

Of note, several research teams investigated mobile phone and Internet use patterns among key populations and in varied settings, suggesting that intervention studies may follow (Table 4). Preliminary work on technology interventions for engagement in HIV care for mothers and infants is underway in both Cameroon [42] and South Africa [43]. Researchers in Kampala, Uganda presented pre-trial findings on acceptability of an mHealth intervention among adolescents living with HIV [44], as well as prevalence and correlates of mobile phone use among youth living in slum areas [45]. One Latin American study assessed feasibility of mHealth among transgender women and men who have sex with men living with HIV in Lima, Peru [46]. Two American studies published early results on technology use patterns and feasibility of technology interventions for HIV care and support among women in the Bronx, New York [47, 48]. Also in New York, researchers performed a content analysis of online interactions in a Facebook group for young people aged 16–25 living with HIV, observing that group participants frequently sought out social support in this context [49]. Notably, these American studies explicitly discussed the potential for digital technologies to provide social support, a shift from much of the existing evidence that has focused on reminders [44]. Finally, related stage-setting work is also being done with adults living with HIV in Soweto, South Africa [50], Nairobi, Kenya [51], Gaborone, Botswana [52], and Anhui, China [53]. Overall, these feasibility and acceptability findings indicate that mobile phones remain the most ubiquitous digital technology especially in low-income settings. However, it is important to consider unique barriers to access in different contexts.

Discussion

Established and emerging evidence on digital technology interventions to support people living with HIV sustain lifelong engagement in care indicate that these are critical tools to help achieve the UNAIDS 90-90-90 targets. However, evidence also demonstrates that not all technological interventions are equally effective. So far, the evidence suggests that weekly, two-way interactive text messaging is likely the most effective intervention, and has the advantage to reach millions of people living with HIV, primarily in sub-Saharan Africa where the HIV burden is highest and basic cellular coverage is nearing ubiquity. Now is the time to scale up programs that are evidence-based, while continuing to innovate for specialized settings and key populations.

Much of the new evidence related to technology interventions for engagement in HIV care has focused on mHealth to support ART adherence. However, several important studies have investigated new areas and applications, such as providing timely laboratory results and supporting retention in care. It is exciting to note that some studies are bringing technology-driven interventions to key populations, including maternal and child health, young people, prisoners, and veterans. Furthermore, although many studies continue to take place in sub-Saharan Africa, recent work in North America, Asia, and Oceania suggests that digital technologies are emerging for engagement in HIV care globally.

Despite these important contributions, notably missing from the evidence are technology interventions that support engagement in care for Indigenous people, migrants, displaced people, people who use drugs, men who have sex with men, transgender women, and sex workers [1, 2]. These are key populations who face significant and complex barriers to HIV care and treatment, including stigma and discrimination in healthcare settings [54–57]. Criminalization of several key populations through laws against sex work, drug use, and same-sex sex further marginalize these groups from care and services [1, 2]. Furthermore, the four million young people aged 15–24 living with HIV globally have been identified as a critical group experiencing multiple barriers to engagement in care, but for whom few targeted interventions are being developed and evaluated [1, 19]. In reaching for the 90-90-90 targets, relegating these key populations to the “10-10-10”, those who are left behind, is a risk. There is a clear need to adapt digital technology interventions to meet the specific needs of these key populations and empower them to engage in lifelong care.

Technology-driven interventions may be powerful tools to reach hard-to-engage groups, if targeted to these key populations. Recent research has shown that by facilitating communication between patients and health services, and supporting connection with peers [48], two-way communication technology is a formidable vehicle for psychosocial support [44, 51, 58, 59]. Others have begun to discuss the power of community input and ownership to develop technology interventions that are valued and acceptable in diverse communities [36, 60–63]. Furthermore, new studies have taken a “whole-person” approach to technological engagement in care interventions that acknowledge and support multiple health needs and priorities, such as co-morbidities and substance use [38•, 60, 61].

Careful consideration of the barriers to technology—which may be the same barriers that prevent people from fully engaging in HIV care—are also vital. For programs to be accessible, clients must either have access to or be provided with the technology at study initiation. Several studies reviewed here observed below-average mobile phone and Internet access within target populations [64]. Digital illiteracy may also be a significant obstacle, including among the elderly. In response, some have provided mobile phones as part of mHealth studies to reach clients that may not have had the opportunity to enroll otherwise [37, 58]. However, struggles with phone loss and participant non-adherence remain a challenge [37, 58]. Furthermore, programs that embrace technologies that are already a part of peoples’ daily lives may be more successful than those that require learning new skills or creating new digital habits.

Conclusion

Reaching the UNAIDS 90-90-90 target has the potential to reduce 90 % of new infections and 80 % of HIV-related mortality by 2030. For these goals to be met, substantial improvements in reducing gaps in care for children, adolescents, and key populations are critical [2]. Technologies for health provide emerging and proven solutions to support achievement of these targets for engagement in HIV care, particularly among the generalized HIV-affected population in sub-Saharan Africa. Simple two-way interactive text messaging, to provide support rather than as a medication reminder, is an evidence-based technological intervention for engagement in care that is able to reach the majority of people with HIV. Opportunities for more complex technological interventions exist in resource-rich settings, and are emerging in resource-limited settings, but current evidence of their effectiveness remains weaker. Additional research is required for tailored technology innovations to support key populations.