Economic and epidemiological evaluation of text message-based interventions in patients with the Human Immunodeficiency Virus

Objective: to evaluate the cost-effectiveness ratio and the budget impact of sending text messages associated with medical consultations in order to reduce the viral load of patients infected with the Human Immunodeficiency Virus. Method: a randomized clinical trial, basis for the development of a dynamic cohort model with Markov states in order to compare medical appointments for adults infected with the Human Immunodeficiency Virus versus the alternative strategy that associated medical consultations to sending text messages through telephone. Results: 156 adults participated in the study. As for the viral load, it was verified that in the control group there was an increase, in the intervention group A (weekly messages) there was a reduction (p = 0.002) and in group B (biweekly messages) there was no statistically significant difference. Sending text messages would prevent 286,538 new infections by the Human Immunodeficiency Virus and 282 deaths in the 20-year period, compared to the standard treatment. The alternative strategy would result in saving R$ 14 billion in treatment costs. Conclusion: weekly sending messages in association with the standard treatment can reduce the circulating viral load due to its effect in decreasing new infections, in addition to reducing health costs.


Introduction
Infections caused by the Human Immunodeficiency Virus (HIV) have shown a progressive increase over time since the first identified cases of the disease (1) .
After the appearance and registration of these cases, dating from the early 1980s, approximately 70 million people contracted the infection and, of these, about 35 million died (1) .
Currently, it is estimated that approximately 37 million people live with HIV in the world, characterizing it as one of the main threats to public health, especially in low or middle income countries (1) . Despite all the progress made in recent years and the reduction of annual infections by 3% in the period from 2007 to 2017, this infection continues to spread throughout the world, leading to 1.8 million new infections/year and 1 million deaths/year (1) .
An example of one of the greatest progresses made in combating this epidemic was the discovery of anti-retroviral treatment (ART) for HIV infection, but its effectiveness and efficiency depend on a series of factors associated with patient compliance. For this reason, the assessment of adherence has been verified by different mechanisms, such as real-time assessment and the verification of the concentration of ART in the hair or blood (2)(3)(4) . The adoption of measures to assess adherence is essential, as inadequate adherence to ART causes an increase in circulating viral load and, consequently, directly interferes in the control of infection and disease progression (3)(4) . In addition, there is an impact on the patient's life expectancy and influence on medical costs related to the progression of the disease, complications, hospitalizations and the treatment of new infections, with adherence being the primary factor for the control of this infection and the early detection of HIV (3) .
In Brazil, ART, as we currently know it, was introduced in 1996 with the principles of universal and free access to the health services and medications, in accordance with the Brazilian health system policy (5)(6) .
This policy has achieved good results, mainly in terms of reducing morbidity and mortality, reducing hospitalizations and treatment costs, leading to rates similar to those of developed countries (5)(6)(7) .
However, this success achieved by Brazilian health policy still faces the poor adherence of patients to ART, which goes beyond free access to treatment, since it depends on the patient's ability to overcome the barriers that negatively impact their adherence (5,(8)(9)(10) . In this sense, there is a need for investment in actions and strategies that can mitigate the cultural, social, and economic differences of these patients, collaborating in improving the adherence and effectiveness of ART, which must be proposed by health services and supported by public health policies (1,4,(9)(10)(11) .
In recent years, some systematic reviews have shown that interventions based on medical consultations, nursing consultations, telephone calls, text messaging, financial incentives and behavioral therapy have improved adherence to ART, but none has carried out an assessment from an economic and epidemiological perspective, aiming to demonstrate how these interventions interfere in the long term in the incidence of new cases (3)(4)9,(12)(13)(14) . In this sense, nonmedication and cost-effective interventions, from an economic point of view, such as sending text messages, can help maintain adherence throughout ART without dispensing high costs to the health system and with easy applicability for large populations regardless of their location and facility to the health system (7,(14)(15) .
In addition, few studies estimate the impact of these interventions on the population scenario, considering their costs and the possibility of reducing new infections.
Thus, this study aimed to assess the costeffectiveness ratio and the budget impact of sending text messages associated with medical consultations in order to reduce the viral load of HIV-infected patients.
Additionally, the number of new infections prevented and the budget impact were evaluated as a way to propose a cost-effective action to improve adherence and decrease HIV infection rates.

Method
This is a randomized controlled trial (RCT) that  the patient should answer this message with a requested number and letter. This confirmation aims to ensure that the study participants were still receiving and reading the messages that were sent to them.
There was no group with daily and monthly messages, based on studies that showed that these sending frequencies are less effective than the weekly or biweekly ones, and the text messages used in the intervention groups are based on the conceptual framework of social support (12,(18)(19) . The messages sent did not inform the diagnosis of HIV infection, respecting the patients' privacy. The messages were sent in the following order based on social support domains and, at the end of the last message (number 6), it returned to the initial message (number 1) (19) : 1) Keep strong. We at the Santa Maria University Hospital care and take care of you.
2) Everyone feels sad at times. Remember that you can talk about depression at your next appointment.
3) Smile, breathe, and go ahead.  The effectiveness data were based on data from the RCT (reduction of viral load) and on data from the literature (general infection rate) (21)(22)(23)(24) . In the model, an estimate was made that, in 2018, approximately 90% of the HIV-infected patients were aware of their serological condition (5) .
The cost data were estimated on the cost of The variables and values used to estimate the parameters for the distributions were described in Table 1.

Results
Initially   The results found in this study are similar to those of other analyses regarding savings in interventions to improve adherence to treatment, which consider the feasibility of screening in the population, nursing interventions, and connectivity through an application to clarify and control patients with HIV (25)(26)(27)(28) . Our conclusions are consistent with the arguments that even interventions with modest effects can be more cost-effective compared to only the usual care and treatments (25)(26)(27)(28) (8,14,(18)(19) .
Sending SMS has been significantly used in the health area, mainly to improve quality of life and attendance in primary care, and to reduce non-adherence and improve health results at low cost, as well as the possibility of wide dissemination of information in real time for the entire target population of the intervention (8,(13)(14)(18)(19)29) .
Additionally, the use of SMS reminders is an accessible, adequate, and more cost-effective tool compared to those already spent on medication (26,(30)(31) .

Conclusion
The analysis of this dynamic cohort reflects that, when implemented at the population level, weekly sending SMS to people infected with HIV and on ART can reduce the circulating viral load and lead to a consequent reduction of new infections, in addition to the reduction of direct costs related to treatment in health.