We performed a randomized clinical trial in which we assessed the efficacy of using SMS text messages to improve treatment adherence. People living with HIV were recruited from the HIV clinic of the tertiary care Hospital Civil de Guadalajara – Fray Antonio Alcalde from February to November 2022. The study included both men and women aged 18 years or older who were diagnosed with HIV and had been on ART for less than 6 months. Additionally, participants needed to have a mobile device capable of receiving SMS text messages and sign the informed consent to participate. Excluded from the study were individuals currently enrolled in another clinical trial, pregnant women, minors, and individuals with a mobile phone capable of receiving SMS messages but lacking coverage or service in their residential area.

The sample size was determined using the OpenEpi software version 3.01, using an anticipated mean difference of 3 percentage points in the rates of adherence between the study groups, based on existing literature [17]. The study was designed with a 95% CI, 80% statistical power, and a 1:1 sample size ratio between the groups being compared. A power analysis was done and determined that a sample size of 29 participants per group was sufficient to detect a mean difference of 3 points in adherence with 80% power and a significance level of .05. Increasing the sample size to 40 participants per group would raise the power to 91%, providing a greater likelihood of detecting a true effect if it exists.

To begin randomization, the protocol nurse generated a table of random numbers in Excel version 16.92 (Microsoft), which was used to assign participants to their respective groups based on whether the randomly generated number was even or odd, at a 1:1 ratio. If a participant who was invited declined the intervention, the allocation sequence proceeded with the next randomly assigned number. This approach ensured that each patient had an equal chance of being allocated to either group, enhancing the randomization process and minimizing selection biases.

Sociodemographic variables were obtained at the time of recruitment using a form that was filled out with the aid of the research team. Viral load and number of CD4+ T cells were measured at the time of enrollment and after the 6-month follow-up. Self-adherence was measured at the 6-month follow-up. To measure adherence, the 4-day adherence index was used, which was calculated using the following formula [18]:

For the measurement of variables, participants were considered employed if they reported engaging in paid work, whether formal or informal. Tobacco, alcohol, and illicit drug consumption were determined if participants reported consumption more than twice a week in the last month. The duration of time living with HIV and the duration on ART were calculated using the study’s completion date.

The intervention consisted of the following procedures. Participants received 2 messages per week on Mondays and Thursdays in the morning during the first 3 months, then 1 message per week for the last 3 months. These messages were prevalidated by a research group and categorized into four types: motivational messages for self-care, reminders for ART collection, reminders for medical appointments, and laboratory reminders. The content encouraged patients to maintain adherence to their medication, provided reminders about upcoming medical visits, and reinforced the importance of regular lab tests, such as CD4 and viral load monitoring. To avoid repetition, the messages were rotated throughout the intervention. The full set of validated messages and their detailed content can be found in the corresponding publication [19].

Additionally, participants received reminder messages for appointments or prescription refills 24 hours before the scheduled date during the 6-month intervention period. Moreover, participants had the option to communicate with the researchers to address any queries, which were resolved through a consensus among the research team with support from relevant departments. To ensure ongoing communication, the telephone line accepted collect messages and collect calls, enabling participants to stay connected throughout the study. Both groups received the standard medical treatment provided by the hospital, which consisted of medical appointments tailored to each patient’s needs, but the appointments were scheduled no more than once every 3 months. The treatment also included free ART with a maximum supply of 90 pills. Additionally, laboratory studies and complementary tests were performed in accordance with national treatment guidelines.

Proportions were analyzed by χ² tests and a Student t test was used for variables. Relative risk based on treatment adherence (>95% or >90%) was measured and the Fisher exact test was used for statistical evaluation. A multivariate analysis was done to calculate relative risks of variables associated with adherence. All statistical analyses were performed on SPSS version 25 (IBM Corp) and an α level of .05 was used to determine significance.

The study protocol was approved by the Ethics Committee in Research of the Hospital Civil de Guadalajara – Fray Antonio Alcalde (registry number 095/18) and was registered as a clinical trial (NCT05187741). In line with the Council for International Organizations of Medical Sciences guidelines, all participants provided written inform consent, which was supplemented by a family witnesses in vulnerable cases to ensure fully informed decision-making. The consent form included all relevant information from the protocol and was supplemented with direct clarification of any concerns to ensure patients fully understood. Participants were informed that they could withdraw from the study at any time without any impact on their access to medical care or other services. Privacy was safeguarded by anonymizing participant data with numerical codes, with only the principal research team having access. In the event of unintentional disclosure, a potential risk identified in our study, psychological support channels were made available. While no monetary compensation was provided, participants benefited from direct access to health care professionals via text or call support, and the treatment also included free ART with a maximum supply of 90 pills.

This study aimed to evaluate the effectiveness of an mHealth intervention on adherence for adults starting ART. As previously mentioned, ART adherence is important for people living with HIV, allowing them to reach viral suppression and increasing their overall quality of life. This highlights the importance of exploring interventions to support patients recently diagnosed with HIV to reach optimal adherence. This study enrolled patients with an age ranging from 30 to 40, which corresponds with the national and worldwide age with the highest HIV prevalence. Also, our participants were mostly men, which aligns with Mexico’s national trend, as men who have sex with men and transgender people are the main groups affected by HIV in Mexico [20].

Both the intervention and control groups shared previously reported factors that can impact adherence like alcohol consumption and being single [5,6,10,21]. Although further analysis of the factors associated with adherence was beyond the scope of this study, our descriptive results provide a preliminary view for further investigations aiming to study the importance of these factors on a patient’s adherence to treatment. Even though the participants were randomly assigned to each group, our intervention group was younger than our control group. We believed that this was related to the recruitment process, as older patients were more likely to reject the invitation of the study due to the concern of using digital conventions over in-person conventions. Giebel et al [22] mention that interventions must be adapted to different age groups due to the diversity of digital health users. These findings need to be explored and contemplated in further studies.

Regarding our clinical findings, the control group had a lower CD4+ T cell count (168 cells/μL), suggesting a delay in HIV detection. The fact that one of our study groups had less than 200 cells/μL highlights the relevance of finding methods to improve early detection in high-risk populations and strategies to prevent low adherence to ART or losses to follow-up [23]. One of the potential implications of these findings is the application of mHealth interventions to provide a faster linkage-to-care after HIV diagnosis, as a previous study has shown that these interventions can reduce the gap between health care clients and institutions to increase retention in care and impact mortality [24].

In this study, we show that mHealth strategies improve adherence to treatment by 4% (P<.001) and increase the probability of reaching a 95% of treatment adherence by 3 times. However, we wanted to evaluate the impact of age and other variables on the probability of reaching 95% treatment adherence. For this, we performed a multivariate analysis, in which the mHealth intervention statistically correlated with ART adherence regardless of other independent variables like age, marital status, and employment. These results suggest that mHealth strategies can be beneficial in multiple scenarios.

As previously demonstrated, simply sending SMS text messages had minimal to no impact on enhancing treatment adherence [25,26]. Therefore, we implemented an mHealth strategy based on the use of interactive SMS text messages, in which the patients had the opportunity to interact by text or phone call with a health professional. Interactive SMS text messages are effective and participants are more likely to engage actively and adhere to their treatment. [27-29]. Another key aspect of the intervention was the frequency of the text messages. The goal was to help establish a habit in the patients while still providing access to assistance if needed. Also, it has been reported that a high frequency of messages over an extended period can become repetitive and lose their beneficial impact [30-32].

Although other studies have used similar strategies, this is the first study in the Mexican population to use an mHealth approach that decreased message frequency to enhance adherence. In addition, we implemented messages that were validated by a Mexican group of health professionals, researchers, and people living with HIV on ART [19]. Few studies looking into the efficacy of mHealth SMS interventions use validated messages for their population [33-35]. Like other studies, we identified an improvement in treatment adherence by using SMS text messages [14,26,36,37]. However, it is important to consider that adherence evaluation was mainly assessed by a self-report that was provided by the patient, which had an intrinsic bias. As a method to address this bias, we measured the HIV viral load along with adherence reported by the 4-day adherence index, which has been reported to have an adequate sensitivity and specificity in Mexican populations [18]. This allowed us to provide a more accurate estimation of adherence levels, as self-reported measures are known to overestimate true adherence levels.

Although we identified an increased adherence using an mHealth strategy, further studies on a larger population are required to confirm our results. It is also important to recognize the variability among different populations and regions [38]. This study was performed in the State of Jalisco, and we found a 93% treatment adherence rate in our control group. This result was similar to another study performed in the state of Mexico that had a 93% adherence rate [39] but double that of a study done in the state of Tamaulipas that had a 46% adherence rate [40]. These state-specific differences highlight how treatment adherence is contextual and is determined largely by the conditions surrounding the patients [41].

This study had some limitations. The evaluation period was relatively brief, lasting only 6 months, which raised uncertainty about the long-term persistence of the intervention’s effect. Additionally, the reliance on self-reported adherence data, without the use of more objective measures such as pill counts at each appointment, introduced the potential for bias. However, the investigators ensured that all participants underwent viral load testing after the study, providing an objective assessment of treatment outcomes.

In summary, this study demonstrates that integrating mHealth strategies as a supplementary approach to existing interventions can enhance treatment adherence among people living with HIV. Additionally, our findings highlight significant results that may inform the implementation of larger and more intricate interventions aimed at bridging the communication gap between health care clients and medical service providers.

This kind of mHealth-based intervention could serve as a precursor for larger-scale interventions aimed at increasing patient adherence and retention for chronic illnesses, which is a significant public health concern that we must address. By leveraging digital health technologies, we can develop more comprehensive strategies to support patients in managing their conditions and improve overall treatment outcomes. Such approaches have the potential to enhance communication between health care providers and clients, thereby promoting better treatment adherence and increasing retention rates across diverse populations with chronic diseases.