Retention in HIV care and adherence to antiretroviral therapy (ART) are the main challenges in preventing HIV-related morbidity and mortality among HIV-infected patients in Mozambique. In 2011, only 74% of patients enrolled in ART programs were still in the program for 12 months after initiating the treatment.1 Evidence from large-scale treatment programs in sub-Saharan Africa demonstrates that retention in care programs and treatment adherence decline over time.2 Despite various interventions to improve patient adherence and retention in HIV care in Mozambique, the number of patients who discontinue treatment is still increasing.1,3 For patients on ART, reduced loss to follow-up has important correlations with better clinical outcomes, including weight gain, recovery of CD4 count, reduction of viral load, and a lower likelihood of resistance, morbidity, and mortality.2–5 In addition, studies have also shown that access to HIV care, initiation of ART, and optimal adherence decrease the risk of sexually transmitting HIV.6
One major challenge with improving HIV treatment efficacy is ensuring that patients adhere to their treatment, including medication and medical check-ups until completion.7 There is hence a need to improve retention in care and adherence to ART. Although there may be many reasons for the lack of adherence, there may be ways to improve the completion of treatment programs by maintaining better contact between health care staff and patients.7
Mobile phone technology has the potential to serve as a strategic intervention medium to improve patient management.8 Owing to the widespread use and low cost of this technology, this technology pervades all age groups, many cultures, and socioeconomic backgrounds, also in developing countries. Mobile phone technology allows communication across geographic boundaries and reaches people directly where they are located.8 Moving across socioeconomic and cultural boundaries, cell phones have revolutionized communication and access to and delivery of information and services.
Several studies have demonstrated the potential of mobile phone text messaging to improve health services and, in turn, health outcomes.9–13 Mobile phone text messaging interventions have proven successful in increasing appointment attendance, increasing treatment adherence for a variety of conditions, disseminating public health information, and improving vaccination rates.9–14 Also, text message reminders have proven to be well suitable for supporting self-management and improvement of patients' self-efficacy skills through, for instance, medication reminders10,15–19 and motivational text messages.10,20
Research about the effects of mobile phone text message reminders on ART, medication, and appointment adherence has shown mixed results, especially in resource-limited settings. Studies from 2 Kenyan trials suggest that text message can improve adherence to ART, reduce viral load, and reduce treatment interruptions.10,21 Another study with patients from Kenya and Cameroon found that text messaging improved adherence to ART [adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.13, 1.88; P = 0.004].22 In the United States, daily text messaging was a feasible and acceptable way to remind HIV-positive youth with poor adherence to ART to take their medications, and there was a significant increase in adherence rates postintervention.23 In Brazil, text messaging improved ART adherence among women living with HIV.24 However, other research has shown no effect of text messaging on health interventions.14 Another study in Cameroon demonstrated that weekly standardized motivational text messages did not significantly improve ART adherence.20 In Scotland, text message appointment reminders for patients who persistently failed to attend their general practice appointments failed to show significant reduction in nonattendance rate.25
Mobile health or m-health interventions are in the early stages in Mozambique, compared, for example, with the burgeoning m-health programmes in neighboring South Africa. To our knowledge, this is the first study in Mozambique to analyze the impact of text message reminders in increasing retention in ART care, and one of the first text message interventions in the public health care system. The Mozambique Ministry of Health has highlighted the importance of m-health to improve the uptake of and retention in health services with future plans for a policy or working group. Data on the efficacy of text message reminders for retention in HIV care remain scarce. To address these problems, we launched SMSaúde, a randomized control trial in 2011, to evaluate the impact of text message reminders on adherence to ART care. The initiative involves a public–private partnership with Vodacom, who provided free text messages, modems, and technical support.
Study Design and Participants
The SMSaúde study was designed to be a 2-arm randomized controlled trial with the intervention being a structured series of text message reminders sent to HIV-infected adult patients on ART from 1 rural and 2 urban government-run health centers in Maputo Province. These health centers were selected by a convenience sample by the Maputo Provincial Directorate of Health to ensure similar quality and access to care across the network and included the following characteristics: availability of ART services for 2 or more years, availability of electronic patient databases (with regular supply of electricity), and availability of cell phone network in the community. The selected health centers included (1) Matola II Health Center (urban), (2) Machava II Health Center (urban), and (3) Namaacha Health Center (rural).
Randomization and Allocation Concealment
The study was launched in November 2011, and the final recruitment took place in March 2012. During the recruitment period, ART patients who presented for clinical consultation in these health centers were interviewed for eligibility and then randomized (1:1) to a control arm (standard care, including defaulter tracing conducted by lay counselors only after patients had defaulted from treatment) or an intervention arm, which received automated text message reminders. Eligibility criteria included 18 years of age or older, currently residing in Maputo Province, plans to reside in Maputo Province for at least 12 months, cell phone ownership, ability to read and write in Portuguese (self-reported), receiving first-line ART, and taking ART for over 15 days. All patients received counseling before the initiation of ART regarding the importance of adherence and access to support groups with other people living with HIV in their community.
To guarantee allocation concealment, before enrollment per health facility, an electronic randomization list was generated with 50% probability to belong to one arm. Only the study's statistician was aware of the study allocation. At recruitment, the counselor invited and enrolled patients. Both the counselors and patients were unaware of the randomization allocation. All clinicians and investigators were blinded to the study allocation. At each day of the recruitment, all recruited study identification and cell phone numbers were entered into the text-message sending system that used the electronic randomization list to send the message. All study staff and clinicians were blinded to randomization.
Participants were followed up from April 2012 for 12 months, and the intervention ended in March 2013. During that period, short text messages were sent to intervention participant's mobile phones. The message content was developed after extensive consultation using focus group discussions with ART patients and separate discussions with clinic staff. The focus group discussions showed that patients often linked happiness with being healthy, a key message that was integrated into the text messages. All messages were less than 160 characters, so they could be received by all types of cell phones. Messages did not specifically mention HIV or ART to maintain confidentiality of HIV status (see Table 1 for messages). We conceptualized the messages and intervention after reviewing behavioral theory around factors associated with retention in care, including distance to health facility, economic priorities, and family factors.
Messages were sent automatically using a modem connected to the cell phone network from each health center. The SMSaúde platform pulled data from the electronic patient database, including upcoming drug pickups and clinical appointments, to send the automatic messages. Messages were divided into 4 categories: general messages (welcome and goodbye messages), appointment reminders, medication reminders, and educational messages. The first message was sent hours later after the health facility was closed. The last message was sent 7 days after the 12-month follow-up or if the patient decided to leave the SMSaúde study. Both appointment reminders and medication reminders were sent 2 and 7 days before the date of clinical appointment and drug pickup. Educational messages were sent every 60 days after the study initiation. The SMSaúde service sent one-way messages to which respondents could respond but would not receive follow-up responses. In the control group, participants did not receive text messages but did receive the standard of care which included oral reminders about their upcoming drug pickups or medical appointments during their follow-up visits.
Patient data were entered into Microsoft Access electronic database which has been widely used in Mozambique since 2007 for the management of patients on ART.26 To ensure data quality, the electronic database contains rules for validating input data (eg, maximum and minimum limits on numerous variables, maximum number of characters). At each study site, data were saved daily on a back-up drive. Each week, a compressed and encrypted copy of the data were placed on a CD-ROM and sent to Absolute Return for Kids' headquarters in Maputo. There the data were incorporated into a central database running on a server prepared for the study, which was used for central monitoring of the evolution of data capturing, input error checking, and regular monitoring of the study.
For the study analysis of demographic (sex, age, residence, marital status, and literacy) and clinical (weight, height, WHO stage, and CD4 absolute count) data, date of last drug pickup, and defaulting status at the end of 12 months was abstracted from the electronic patient database.
Baseline data analysis of participants were summarized as median and quartiles for continuous variables, and number and percent for categorical variables. The primary outcome was retention in HIV care at 12 months of follow-up. The second outcome was attrition (loss to follow-up from HIV care). Loss to follow-up from care was defined as having occurred when more than 60 days elapsed since the last documented drug pickup or clinical visit (Ministry of Health definition). By the time the trial was designed, the estimated retention in ART post 12 months of ART was 88%. Under that retention figure, the required sample size to detect a 50% decrease in hazard rate of defaulting with 80% power at an alpha of 5% was 860 and 72 patients lost to follow-up. These calculations were implemented using the stpower log-rank command from Stata 11. The overall sample was then distributed proportionally to volume of patients in ART of the chosen sites.
We computed the proportion of retention in care as the complementary of the cumulative proportion of defaulting from treatment, obtained from Kaplan–Meier estimator. Difference of these retention proportions are calculated and tested whether they were different from 0 through a z-test. Rates of attrition were computed per 100 person-time follow up and differences and ratios between groups are compared through exact Poisson methods. Also, Cox proportional hazards models were used to evaluate the interaction of the intervention and a dummy variable indicating newly/long-time initiated ART (<3 months or >3 months on ART). All analysis were stratified by urban/rural health center. Primary analysis was by intention to treat. Data were analyzed using Stata 11 (Stata: Release 11, Statistical Software; StataCorp. 2009, StataCorp LP, College Station, TX).
All eligible participants provided their informed consent to participate in the study, which was approved by the National Bioethics Committee for Health (CNBS) of the Ministry of Health in Mozambique (IRB#: 00002657). Participants were informed about the randomization of the study and that they had a 50/50 chance of receiving regular text message reminders and educational messages for the upcoming 12 months. The study was registered at Clinicaltrials.gov NCT01910493.
Recruitment, Participant Flow, and Characteristics of the Study Population
Of the 1201 ART patients who were interviewed in the 3 selected health centers between November 2011 and March 2012, 830 (69%) were deemed eligible and enrolled. The major barriers to study eligibility were illiteracy (n = 140, 38%), lack of ownership of a cell phone (n = 99, 27%, of whom 82% were women), or both reasons (n = 106, 29%). Other reasons for exclusion (n = 21, 6%) included not living in the area or plans to move within the upcoming 12 months. Participants were randomized 1:1 to either the control (n = 414) or intervention group (n = 416) (Fig. 1).
Women accounted for 59.9% of the cohort; 73.5% in the rural facility vs. 57.3% in the urban facilities (data not tabled). The median age was 36.9 years [interquartile range (IQR) 31.3–44.9], and the median time on ART was 13.7 months (IQR 4.2–26.6). Most participants had attained a primary level of education (73.5%), whereas 23.5% had attained a secondary or technical education level. More than half of the participants were either married or cohabited with a partner (57.4%), whereas one-third were single (34.7%); the remaining participants were widowed (7.7%). The details of participant characteristics are reported in Table 2. There were no differences between the control and intervention groups for any of the baseline sociodemographic variables.
Retention of Participants
Overall, the retention in ART care was higher in the intervention group (93.8%, 95% CI: 90.5 to 95.7) than the control group (91.0%, 95% CI: 87.7 to 93.4); however, text message reminders had a nonsignificant impact on retention in ART care (rate difference = 2.8, 95% CI: −0.9 to 6.4, P = 0.139). The retention among urban patients was also higher in the intervention group (94.3%, 95% CI: 91.3 to 96.4) than in the control group (89.9%, 95% CI: 86.1 to 93.1; rate difference = 4.4, 95% CI: 0.4 to 8.5, P = 0.032). Among rural patients, retention was higher in the control group (96.8%, 95% CI: 87.9 to 99.2) than in the intervention group (90.7%, 95% CI: 08.4 to 95.7), although this difference was not statistically different (rate difference = 26.1, 95% CI: 214.5 to 2.2, P = 0.148) (Table 3).
Overall, the attrition incidence was 9.5 in the control group (95% CI: 6.8 to 13.1) vs. 6.4 (95% CI: 4.3 to 9.5) in the intervention group per 100 person-years on ART, although it was not statistically different [incidence rate ratio (IRR) 0.68, 95% CI: 0.41 to 1.13, P = 0.139]. Among urban patients, those in the intervention group had a lower attrition incidence (attrition incidence = 5.8, 95% CI: 3.7 to 9.1) compared with patients in the control group (attrition incidence = 10.7, 95% CI: 7.6 to 15.0; IRR = 0.54, 95% CI: 0.31 to 0.95, P = 0.031). Among rural patients, attrition incidence was not different between the standard of care and text message reminder group (IRR = 3.10, 95% CI: 0.63 to 15.34, P = 0.166) (Table 3).
Among those who recently initiated ART (≤3 months), the risk of attrition in HIV care among patients who received text message reminders was one-third of that in the control arm [hazard ratio (HR) = 0.33, 95% CI: 0.12 to 0.91, P = 0.033] and was the lowest in urban patients newly initiated on ART (HR = 0.20, 95% CI: 0.06 to 0.64, P = 0.006) and among non-newly initiated urban patients who received text messages (HR = 0.34, 95% CI: 0.12 to 0.96, P = 0.04). Rural patients who received text messages did not have any differences in attrition (Table 4).
Our study demonstrated that regular text message reminders and educational messages did not improve retention in HIV care overall among patients on ART in Mozambique. In post hoc analysis, weekly text message reminders were effective at improving the retention in care among urban patients and among the patients who had recently initiated ART. Overall retention in the study, and in ART care, was excellent, with approximately 90% remaining in care when compared with 74% in the government health facilities in 2011 as measured by patients enrolled in ART program 12 months after initiating the treatment.1 In our study, text messages had no effect on rural retention in HIV care. A variety of factors likely contributed to the observed lack of impact in rural areas. These factors could include underlying transport constraints in rural areas (increased distance from health facility was significantly associated with discontinuing treatment in the rural cohort); poor location of the selected rural health center (near an international border with Swaziland, where cell phone network was weak); likely frequent migration away from the facility sites; problems with consistent cell phone network coverage; and poor access to electricity, which limits the participants' ability to charge their cell phones.
Other studies found that treatment supports such weekly text message messages (vs. daily text message messages), increased counseling, and text message combined, and treatment supporters were effective at improving ART adherence compared to the standard of care.11 A recent US study among adolescents and young adults found that self-reported ART adherence was higher among those who received personalized daily text messages.12 Furthermore, a systematic review found that text message reminders can help improve adherence in other chronic diseases such as diabetes or infectious diseases such as tuberculosis.27 Text messaging have been shown to improve attendance at appointments and behavior change outcomes.27 However, adherence to ART is easily improved by text message as generally the drugs are at home and reminder suffices. However, retention includes more logistical and structural determinants (transport, absence from work, migration, and others) than simply addressing treatment adherence. This is a strength of our study, as we analyzed retention in HIV care in urban and rural government clinics, and we did not limit our intervention to adherence to medication.
More research is needed to explore avenues to improve access to mobile health, or m-health, interventions in illiterate women, such as the use of family cell phones. Past research has shown that women in low-income countries are 21% less likely to own a cell phone than men. This gender gap represents at least 300 million women in the developing world without access to a potential life-enhancing tool.28 In 2011, 29% of the Mozambique population owned a cell phone, and the majority of cell phone owners today are men. As we expand our study, we intend to explore the possibility of family cell phone ownership of a cell phone for inclusion in the study because many women have husbands or other family members with cell phones. We will also explore the use of voice messaging to improve the reach among illiterate populations. Designing m-health strategies in rural contexts remains a challenge because of weak infrastructure, illiteracy, and poor cell phone penetration. The role of community health workers in delivering educational messages and referring back to health services is also considered. We intend to address these challenges in an upcoming study of the rural population. There is also a need to do a cost effectiveness analysis to understand the financial implications of scaling up a SMS model vs. other adherence support models.
There are several limitations to our study including the short time frame, the limited geography and hence limited generalizability of the study, and limited study eligibility. The study only followed patients for 12 months. Study results are thereby limited to short-term follow-up. The limited area of the Maputo Province did not allow us to include rural areas that are not on the national border or areas with poor cell phone coverage, which is typical in most rural areas of Mozambique. Finally, this intervention was limited to literate patients with mobile phones. Despite these limitations, the study found that text message reminders improved retention in care among urban and newly enrolled ART patients in Mozambique.
Furthermore, research on text messaging has shown that sending too frequent, overly long, and repetitive text message reminders can lead to habituation.29,30 Boredom or a reduction in novelty can result in diminishing effect on adherence to whatever behavior change the text message is trying to promote. Similarly, at the start of a study or intervention, patients may be enthusiastic and interested in the novel process (because it is intrinsically pleasing), which could diminish over time as the novelty wanes.31–34 As a result, longer-term studies of outcomes are needed to evaluate the impact of boredom, or novelty may have on the participants.
Our study showed that retention in HIV care among patients on ART in Mozambique was unchanged among those who received regular text message reminders over 12 months. We did find that text message reminders did impact retention in care among urban patients and among patients who had started on treatment within the past 3 months, when patients are more likely to drop out of care and/or treatment. However, prominent knowledge gaps include the absence of research on cost-effectiveness, long-term outcomes, and patient satisfaction. More research is needed to understand whether text messaging can improve HIV care for HIV-infected individuals before they initiate ART. We will continue to work on improving the reach of this technology-based solution to other populations.
The authors acknowledge the time and collaboration from the patients and their family, the health care team staff, data collectors and analysts, the Mozambican Ministry of Health, and Vodacom. J.A.N. wishes to acknowledge the support of his Professors Gunnar O. Klein and Åke Grönlund.
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