This paper is in the following e-collection/theme issue:

Mobile Health (mhealth) (3464) Text-messaging (SMS, WeChat etc)-Based Interventions (751) mHealth for Screening (296) Mobile Health Technology and Digital Platforms for Public Health (54) Sex education, sex behavior and pregnancy/STD prevention for Adolescents (130) Risky Sexual Behavior (175) HIV/AIDS/STI Prevention and Care (1043) LGBTQ Issues (543)

Published on in Vol 27 (2025)

Preprints (earlier versions) of this paper are available at https://preprints.jmir.org/preprint/72360, first published .
Weekly Text Messages to Support Adherence to Oral Pre-Exposure Prophylaxis (PrEP) Among Gay, Bisexual, and Other Cisgender Men Who Have Sex With Men (MSM) and Transgender Women: Pilot Randomized Controlled Trial Nested in PrEP Brasil Study

Weekly Text Messages to Support Adherence to Oral Pre-Exposure Prophylaxis (PrEP) Among Gay, Bisexual, and Other Cisgender Men Who Have Sex With Men (MSM) and Transgender Women: Pilot Randomized Controlled Trial Nested in PrEP Brasil Study

Weekly Text Messages to Support Adherence to Oral Pre-Exposure Prophylaxis (PrEP) Among Gay, Bisexual, and Other Cisgender Men Who Have Sex With Men (MSM) and Transgender Women: Pilot Randomized Controlled Trial Nested in PrEP Brasil Study

Authors of this article:

Luana Monteiro Spindola Marins1 Author Orcid Image ;   Thiago Silva Torres1 Author Orcid Image ;   Ronaldo Ismerio Moreira1 Author Orcid Image ;   Iuri Costa Leite2 Author Orcid Image ;   Marcelo Cunha2 Author Orcid Image ;   Brenda Hoagland1 Author Orcid Image ;   Lucilene Araujo Freitas1 Author Orcid Image ;   Debora Castanheira1 Author Orcid Image ;   Carolina Coutinho1 Author Orcid Image ;   Emilia Moreira Jalil1 Author Orcid Image ;   Mayara Secco Torres Silva1 Author Orcid Image ;   Jose Valdez Madruga3 Author Orcid Image ;   Beatriz Grinsztejn1 Author Orcid Image ;   Valdilea Gonçalves Veloso1 Author Orcid Image
Article Authors Cited by Tweetations Metrics

    1Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Av Brasil 4365 Manguinhos, Rio de Janeiro, Brazil

    2Escola Nacional de Saúde Pública Sérgio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

    3Centro de Referência e Treinamento DST/AIDS, São Paulo, Brazil

    *these authors contributed equally

    Corresponding Author:

    Thiago Silva Torres, PhD


    Background: Mobile phones have become popular tools to support public health interventions (mobile health [mHealth]). Text messaging, including SMS, is a simple, low-cost approach for health communication to a large population and offers valuable tools in improving health outcomes. Despite the global advances in HIV treatment and prevention, the HIV epidemic continues to disproportionately affect certain populations such as men who have sex with men (MSM) and transgender women, including in Latin America.

    Objective: This study aimed to evaluate the effectiveness of SMS text messaging in improving adherence after 1-year provision of oral pre-exposure prophylaxis (PrEP) among MSM and transgender women in Brazil.

    Methods: Pilot randomized controlled trial nested in the PrEP Brasil study, a prospective, multicenter, open-label implementation study assessing PrEP delivery in the context of the Brazilian Public Health System. Those who agreed to participate in the pilot trial were randomized 1:1 to standard-of-care (SOC) or intervention (SMS text messaging) arm. SMS text messages were launched fully automated weekly to participants for 48 weeks. Adequate adherence to PrEP has been defined as having (1) tenofovir-diphosphate concentration of ≥700 fmol/punch, (2) medication possession ratio of ≥1.07, (3) pill count of ≥90.1%, and (4) self-report (structured questionnaire) of ≥99.9%. Adequate adherence outcomes at week 48 were compared between arms (SMS text messaging vs SOC) using univariate logistic regression. Comparisons were also performed for young MSM aged 18‐24 years and transgender women.

    Results: From 450 participants enrolled on PrEP Brasil, 417 (92.7%) were randomized to the pilot trial: 210 to SOC and 207 to SMS arm. Until week 48, participants received a total of 14,099 SMS with the text message: “Are you okay?,” and 6959 (49.4%) messages were replied. Of these, the vast majority replied “Yes” (6762/6959, 97.2%). A total of 347 (83.2%) participants completed the study with no difference between arms for the 4 adherence outcomes. Conversely, young MSM who received SMS text messages had 2.50 increased odds of having adequate PrEP adherence measured by medication possession ratio (P=.05). Most participants found SMS text messaging very useful or useful (127/167, 76.0%) and would recommend SMS text messaging as a support strategy for persons using PrEP (134/167, 80.2%). Most participants think that SMS text messaging should be offered to all persons using PrEP (129/167, 77.2%), and 16.2% (27/167) think that SMS text messaging should be offered only to those persons using PrEP with adherence problems. Weekly messages were found adequate by 80.2% (134/167).

    Conclusions: SMS text messaging intervention improved adequate PrEP adherence among young MSM and can be a useful tool for PrEP coverage and persistence. Future interventions using other mHealth tools such as WhatsApp messages and apps tailored to support PrEP adherence should be evaluated among MSM and transgender women in Brazil.

    Trial Registration: ClinicalTrials.gov NCT01989611; https://clinicaltrials.gov/study/NCT01989611

    J Med Internet Res 2025;27:e72360

    doi:10.2196/72360

    Keywords

    HIV; mHealth; digital health; Latin America; LGBTQIAPN+ 


    Despite the global advances in HIV treatment and prevention, the HIV epidemic continues to disproportionately affect certain key populations such as gay, bisexual, and other men who have sex with men (MSM), and transgender women. Estimated proportions of new adult infections in 2010 and 2022 increased for MSM and transgender women across all regions [1]. In Latin America, the number of new HIV cases has increased between 2010 and 2023, highlighting persistent challenges in controlling the epidemic [2]. In Brazil, recent data indicate an increasing HIV prevalence among young MSM aged 18‐24 years [3,4]. The estimated annualized HIV incidence among MSM and transgender women in the country was 2.62% (95% CI 1.78‐3.43), being higher among young persons aged 18‐24 years (3.48%, 95% CI 1.99‐4.94) [5]. Recently, HIV prevalence was estimated at 10% in a respondent-driven sampling–based study among young MSM aged 18‐24 years in Rio de Janeiro, Brazil [6].

    The safety and efficacy of oral pre-exposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate in reducing the risk of HIV acquisition [7-10] and the relationship between PrEP adherence and protective efficacy have been well demonstrated [11-13]. During the ImPrEP study, the largest PrEP implementation study in Latin America, HIV incidence was higher among those with lower adherence measured by medication possession ratio (MPR) [14]. Additionally, adherence was lower among younger participants (aged 18‐24 years), transgender women, persons self-identifying as Black, and those with lower education [14,15].

    The rapid growth of mobile technologies and their popularity worldwide led to solutions to address problems within health care systems (mobile health [mHealth]). Thus, mobile phones have become popular tools to support medical or public health, offering new possibilities for diagnosis, treatment, interventions, mHealth apps, and training [16]. Text messaging, including SMS, is a simple, low-cost approach for health communication to a large population and offers valuable tools in improving health care outcomes. In an umbrella review of 34 meta-analyses, representing 235 randomized controlled trials across 52 countries and 48,957 participants, text messages were effective for populations with chronic diseases, including for medication adherence among people living with HIV [17]. In Brazil, results from a randomized controlled trial indicated that SMS text messaging improved antiretroviral therapy adherence among cisgender women living with HIV [18]. In this sense, there is a broad interest in the scientific development and use of mHealth in HIV prevention [19].

    Although adherence is a requisite to PrEP protection, few studies evaluating mHealth interventions to support PrEP adherence were conducted in Latin America [20]. Qualitative findings from a study conducted among young MSM aged 18‐24 years in Brazil have shown high acceptability of weekly text messages to improve PrEP adherence [21]. In this sense, the aim of this study was to evaluate the effectiveness of weekly SMS text messaging in improving adherence after 1-year provision of oral PrEP among MSM and transgender women in Brazil.


    Study Design

    Randomized controlled pilot trial (SMS substudy) nested in PrEP Brasil study, a prospective, multicenter, 48-week open-label implementation study assessing PrEP delivery for MSM and transgender women at higher vulnerability for HIV in the context of the Brazilian Public Health System (Sistema Único de Saúde). Details of the PrEP Brasil study design and results were published elsewhere [22-26]. Briefly, participants were recruited in 3 sites in Rio de Janeiro and São Paulo, Brazil. They completed a structured sociobehavioral questionnaire and received 1 bottle containing 30 pills of tenofovir disoproxil fumarate for PrEP at enrollment. Subsequently, participants received a sufficient supply of pills for daily use at weeks 4, 12, 24, and 36. Study pharmacists instructed the participants to take 1 daily pill and to return remaining PrEP pills in the original bottle to the pharmacy for accountability. At each study visit, the pharmacists and psychologists provided adherence support and counseling as standard of care (SOC).

    The SMS substudy was offered to all participants enrolled in the PrEP Brasil study. Individuals were eligible if they had an SMS text messaging–capable mobile phone and were willing to use this phone for receiving study text messages. Eligible participants were randomized 1:1 to SOC arm or SOC plus weekly SMS text messages (SMS arm). The data manager used block randomization (n=10) to ensure an unbiased allocation into the 2 arms. The data manager prepared individual assignment cards that indicated the group allocation for each eligible participant. Each assignment card was placed in a sealed opaque envelope to conceal the group allocation. Then, each envelope was assigned a unique identification number corresponding to its sequence in the randomization process. During enrollment, site study coordinators accessed the next numbered envelope in sequence to assign each participant’s arm. Pharmacists and psychologists providing SOC were blinded after the study arm assignment. All participants received the intended care, regardless of allocated arm. The SMS substudy was approved by the institutional review boards at Instituto Nacional de Infectologia Evandro Chagas (INI-Fiocruz), Universidade de São Paulo, and Centro de Referência e Treinamento DST/AIDS de São Paulo. All participants provided written consent to participate in the substudy. This study was registered at clinicaltrial.gov, NCT01989611 (November 21, 2013) and follows CONSORT-EHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth) guidelines (the CONSORT-EHEALTH checklist is provided in Checklist 1).

    Sample Size

    All participants from the PrEP Brasil study were invited to the SMS substudy, with no prior sample size calculation. A systematic review from 2012 reported that the mean proportion of participants with oral PrEP adequate adherence was 87%, ranging from 69% to 97% [27]. Based on this, a sample size of 153 participants per arm was deemed sufficient to provide 90% power to detect a 10-percentage-point difference in adherence rates, using a 2-sided test at the 5% significance level. In the TAPIR study, a randomized controlled trial assessing oral PrEP adherence at week 48 compared daily SMS text messaging intervention with SOC. Approximately 200 participants per arm were enrolled, with 324 participants retained at week 48. This sample size was calculated to detect a 15% difference in adherence between the arms, assuming 68% adherence in the SOC group, with 94% power, and a 2-sided α value of .05 [28].

    SMS Text Messaging and Messaging System Platform

    INI-Fiocruz Information Technology staff developed an automated password-protected messaging system platform. This platform had technical safeguards to protect participant information and confidentiality as only authorized study staff (including the study coordinator) using a personal username and password had access. The study coordinator included the participants’ mobile numbers allocated to the SMS arm into the platform. Through the password-protected platform database, the authorized staff could supervise the SMS text messages exchanged with the participants. The platform access and integrity could be monitored and audited only under authorized staff supervision.

    All participants allocated to the SMS arm received a morning weekly SMS text message (“Are you okay?” in the local language) from the automated platform after baseline visit, starting on week 1 until week 47. The SMS text message content (“Are you okay?”) was purposefully chosen for its neutral tone, ensuring that it did not disclose participants’ involvement in the study or their engagement with HIV prevention services. Our primary objective was to safeguard participant confidentiality and reduce the risk of unintended disclosure to third parties, which could potentially lead to negative social consequences [29,30].

    Participants were instructed to respond “Yes” or “No.” Those who answered “Yes” received an acknowledgment “Thank you” text message. The study coordinator contacted all participants replying “No” within 48 hours and provided adherence support. The platform automatically sent a second SMS text message at night for the participants not responding to the initial SMS text message. The study coordinator contacted by phone call all participants not responding for 3 consecutive weeks (Figure 1). SMS text message response was charged to participants according to their mobile plan; participants did not receive a budget from the study. We instructed the participants not to use SMS text messages for medical emergencies. Instead, they were instructed to contact the study site by phone or proceed immediately to the site.

    ‎
    Figure 1. PrEP Brasil SMS substudy design flowchart. PrEP: pre-exposure prophylaxis.

    Adherence Outcomes

    Adherence was measured at week 48 in the PrEP Brasil study using four different methods: (1) tenofovir-diphosphate (TFV-DP) levels, (2) MPR, (3) pill count, and (4) self-report. TFV-DP levels were measured on blood from dried blood spots, using liquid chromatography-mass spectrometry tandem mass spectrometry at the University of Colorado Antiviral Pharmacology Laboratory using standard procedures [13]. In a previous analysis using data from PrEP Brasil, we found concordance between TFV-DP levels and indirect adherence measures (MPR, pill count, and self-report) [24]. Considering these prior findings, we incorporated all 4 adherence measurement methods in our analysis, acknowledging that indirect methods are more affordable and accessible, making them more feasible for real-world implementation. MPR reflects the days the participant is “covered” by the study medication. It is calculated by the ratio of the number of pills dispensed at the prior visit and the number of days between that visit and the week 48 visit. For participants who missed the week 36 visit, MPR and pill count at week 48 were calculated based on data from their most recent attended visit. MPR values of 1.00 or greater indicate 100% PrEP coverage, and values below 1.00 reflect that the participant was not covered by PrEP during all the days between week 48 and the prior visit [14,24]. Pill count was calculated by the number of pills dispensed at the prior visit minus the number of pills returned at week 48, divided by the number of days between the 2 visits. Finally, self-report was assessed using 1 question from a structured questionnaire (“On average for how many days did you forget to take your PrEP pills in the previous 30 days?") administered by study pharmacists. The iPrEX Open-label study demonstrated that TFV-DP concentration of ≥700 fmol/punch, corresponding to ≥4 doses per week, was associated with a 100% (95% CI 86%-100%) reduction in HIV transmission [13]. In addition, based on our group’s previous exploratory analysis to determine the cutoff points for each indirect adherence measure [24], we defined adequate PrEP adherence at week 48 as (1) TFV-DP concentration of ≥700 fmol/punch, (2) MPR of ≥1.07, (3) pill count of ≥90.1%, and (4) self-report of ≥99.9%.

    SMS Text Message Acceptability Assessment

    Participants allocated to SMS arm completed a structured questionnaire about SMS text message acceptability at week 48. Participants responded to predefined multiple-choice questions regarding usefulness of SMS text message service, frequency of SMS text messages, problems receiving or sending SMS text message, and platform preference (email or SMS text message). The responses were summarized as frequencies and percentages.

    Statistical Analysis

    We conducted initial descriptive analyses to compare baseline characteristics, the randomization of participants, and the distribution of variables. PrEP adherence outcomes at week 48 were compared between arms (SMS vs SOC) using univariate logistic regression (odds ratio and 95% CI). We also compared PrEP adherence outcomes at week 48 between arms for 2 groups: young MSM (aged 18‐24 years) and transgender women. Analyses were conducted using SAS (version 9.4; SAS Institute).

    Ethical Considerations

    INI Evandro Chagas-FIOCRUZ institutional review board has approved this study (no. CAAE08405912.9.1001.5262 at ‘‘Plataforma Brasil’’) and all study participants have signed an informed consent form. Institutional review boards at CRT-AIDS and Universidade de São Paulo also approved the study after first approval had been granted at Fiocruz.


    From April 2014 to July 2016, 450 participants were enrolled and followed for 48 weeks in the PrEP Brasil study. Of these, 31 (6.9%) participants refused to participate in the SMS substudy, and 2 (0.4%) were ineligible (no personal mobile phone to receive SMS text messages). Thus, 417 participants were included and randomized in the SMS substudy to SMS arm (N=207) and SOC arm (N=210) (Figure 2).

    ‎
    Figure 2. CONSORT (Consolidated Standards of Reporting Trials) flow diagram of the PrEP Brasil SMS substudy. PrEP: pre-exposure prophylaxis.

    Baseline characteristics of participants included in the SMS substudy (N=417) according to arm are described in Table 1. Overall, the median age was 30 years (IQR 25‐35 years); 102 (24.5%) participants were aged 18‐24 years. The majority self-identified as cisgender men (392, 94.0%) and 25 (6.0%) as transgender women. More than half (246, 59.0%) were from São Paulo and White (224, 54.4%), and 307 (73.6%) completed 12 years or more of schooling. Regarding sexual behavior 3 months prior to the baseline visit, 184 (44.1%) participants reported condomless receptive anal sex, and 205 (49.2%) participants reported sex with partners living with HIV. A total of 82 (19.7%) participants have at least 1 sexually transmitted infection diagnosed at baseline. Most participants reported binge drinking (250, 60.0%), while 79 (18.9%) participants reported use of stimulants.

    Table 1. Baseline characteristics of participants enrolled in the PrEP Brasil SMS substudy according to arm (SMS text messaging vs standard of care).
    CharacteristicsSMSSOCaTotal
    Total, n (%)207 (49.6)210 (50.4)417 (100)
    Site location, n (%)
     Rio de Janeiro85 (41.1)86 (41.0)171 (41.0)
     São Paulo122 (58.9)124 (59.0)246 (59.0)
    Age (years), n (%)
     18‐2460 (29.0)42 (20.0)102 (24.5)
     25‐3590 (43.5)111 (52.9)201 (48.2)
     >3557 (27.5)57 (27.1)114 (27.3)
    Gender, n (%)
     Cisgender men195 (94,2)197 (93,8)392 (94.0)
     Transgender women12 (5.8)13 (6.2)25 (6.0)
    Race, n (%)
     White109 (53.4)115 (55.3)224 (54.4)
     Black23 (11.3)29 (13.9)52 (12.6)
     Pardo or Mixed72 (35.3)64 (30.8)136 (33.0)
    Schooling (years), n (%)
     <1256 (27.1)54 (25.7)110 (26.4)
     ≥12151 (72.9)156 (74.3)307 (73.6)
    Condomless receptive anal sex, n (%)b
     Yes89 (43.0)95 45.2)184 (44.1)
     No118 (57.0)115 (54.8)233 (55.9)
    Sex with partners living with HIV, n (%)b
     Yes104 (50.2)101 (48.1)205 (49.2)
     No103 (49.8)109 (51.9)212 (50.8)
    STIc diagnosis, n (%)d
     Yes39 (18.8)43 (20.5)82 (19.7)
     No168 (81.2)167 (79.5)335 (80.3)
    Binge drinking, n (%)b,e
     Yes127 (61.4)123 (58.6)250 (60.0)
     No80 (38.6)87 (41.4)167 (40.0)
    Use of stimulants, n (%)b,f
     Yes38 (18.4)41 (19.5)79 (18.9)
     No169 (81.6)169 (80.5)338 (81.1)

    aSOC: standard of care.

    bPrior 3 months before baseline visit.

    cSTI: sexually transmitted infection.

    dAny positive laboratory diagnosis for syphilis, gonorrhea, or chlamydia at screening.

    eFive or more drinks in a couple of hours.

    fCocaine, crack, amphetamines, or club drugs (ecstasy, LSD, ketamine, and GHB).

    Until week 48, participants received a total of 14,099 SMS with the text message: “Are you okay?,” and 6959 (49.4%) messages were replied (Table 2). Of these, the majority replied “Yes” (6762/6959, 97.2%) and 169 (2.4%) replied “No.” Most participants answering “No” reported health-related problems and were referred for an unscheduled visit (108/169, 63.9%). We performed 776 phone contact attempts for the SMS text message not replied to after 3 consecutive weeks. Of these, 268 (34.5%) were successful, and the main reason reported was an inability to receive the messages (56, 20.9%). The proportion of participants responding to SMS text messages remained relatively consistent over the weeks, with response rates fluctuating slightly around 70% (Figure 3).

    Table 2. Description of SMS text messages delivered during the PrEP Brasil SMS substudy.
    SMS text message
    Replied SMS text message (n=14,099), n (%)
     Yes6959 (49.4)
     No7140 (50.6)
    Are you okay? (n=6959), n (%)
     Yes6762 (97.2)
     No169 (2.4)
     Nonstandard answer28 (0.4)
    Reasons for replying “no” (n=169), n (%)
     Health-related problems; participant referred for an unscheduled visit108 (63.9)
     Personal problems21 (12.4)
     Needing some type of guidance3 (1.8)
     Not using PrEPa; referred to study termination visit2 (1.2)
     Did not answer35 (20.7)
    Successful phone contacts (participants not replying for 3 consecutive weeks) (n=776), n (%)
     Yes268 (34.5)
     No508 (65.5)
    Reasons for not replying SMS text message (n=268), n (%)
     Inability to receive the messages56 (20.9)
     Unwillingness to answer44 (16.4)
     No available credit on prepaid phone37 (13.8)
     Mobile phone device problems34 (12.7)
     Personal problems30 (11.2)
     Difficulties replying to messages29 (10.8)
     Desire to withdraw the study15 (5.6)
     Had a scheduled visit close by13 (4.9)
     PrEP Brasil study discontinuation7 (2.6)
     Problems with daily routine2 (0.7)
     Health-related problems1 (0.4)

    aPrEP: pre-exposure prophylaxis.

    ‎
    Figure 3. Proportion of participants replying to weekly SMS text messages over 48 weeks (PrEP Brasil SMS substudy).

    A total of 347 (417, 83.2%) participants completed the study (week 48), with no difference between arms (SMS text messaging: 177 vs SOC: 170; P=.21). Out of 347 participants, 12 (3.5%) participants did not attend the week 36 visit; hence, data from their most recent prior visit were used for MPR calculation. Considering all participants (overall), the proportion of participants with adequate PrEP adherence at week 48 did not differ between arms for all evaluated outcomes: TFV-DP levels, MPR, self-report, and pill count (Table 3). For young MSM, we found a difference between arms only for MPR: participants at the SMS arm had 2.50 increased odds (95% CI 1.01‐6.17) of having adequate PrEP adherence measured by MPR than those at the SOC arm (P=.05). For transgender women, we found no difference between arms for all PrEP adherence outcomes.

    Table 3. Proportion of participants with adequate pre-exposure prophylaxis adherence at week 48 according to allocated arm (SMS text messaging vs standard of care) and comparison between arms in the PrEP Brasil SMS substudy.
    SMS, n (%)SOCa, n (%)ORb (95% CI)P value
    Overall (N=347)
    TFV-DPc levels177 (75.1)170 (73.5)1.09 (0.67‐1.76).73
    MPRd177 (63.8)170 (60.0)1.18 (0.76‐1.82).46
    Self-report166 (57.8)155 (60.0)0.91 (0.59‐1.43).69
    Pill count165 (67.9)156 (68.0)1.00 (0.62‐1.59).99
    Young MSMe (18‐24 years) (n=81)
    TFV-DP levels46 (80.4)35 (68.6)1.88 (0.68‐5.22).22
    MPR46 (65.2)35 (42.9)2.50 (1.01‐6.17).05
    Self-report40 (52.5)28 (53.6)0.96 (0.36‐2.52).93
    Pill count42 (66.7)28 (57.1)1.50 (0.56‐4.02).42
    Transgender women (n=21)
    TFV-DP levels11 (45.4)10 (80.0)0.23 (0.02‐1.94).24
    MPR11 (45.4)10 (70.0)0.38 (0.04‐2.89).49
    Self-report10 (20.0)10 (50.0)0.27 (0.02‐2.47).35
    Pill count10 (20.0)10 (50.0)0.27 (0.02‐2.47).35

    aSOC: standard of care.

    bOR: odds ratio:

    cTFV-DP: tenofovir-diphosphate.

    dMPR: medication possession ratio.

    eMSM: men who have sex with men.

    A total of 167 participants completed the SMS text message acceptability assessment (Table 4). Most participants found SMS text messaging service very useful or useful (127/167, 76.0%) and would recommend SMS text messaging as a support strategy for persons using PrEP (134/167, 80.2%). Most participants think that SMS text messaging should be offered to all persons using PrEP (129/167, 77.2%), and 16.2% (27/167) of participants think that SMS text messaging should be offered only to those persons using PrEP with adherence problems. Weekly messages were found adequate by 80.2% (134/167). Only 22.8% (38/167) had problems sending or receiving SMS text messages, and the most common reason was lack of prepaid credit (8/38, 21.1%). Only 11.4% (140/167) of participants would prefer to receive support messages via email rather than SMS text messaging.

    Table 4. SMS text message acceptability assessment in the PrEP Brasil SMS substudy (N=167).
    Values, n (%)
    Overall, how would you rate the usefulness of the SMS text messaging service?
    Very useful71 (42.5)
    Useful56 (33.5)
    Somewhat useful26 (15.6)
    Not useful12 (7.2)
    Missing2 (1.2)
    Which statement best describes how you feel?
    SMS text messaging should be offered to all persons using PrEPa129 (77.2)
    SMS text messaging should be offered only to those persons using PrEP with adherence problems27 (16.2)
    SMS text messaging should not be offered as PrEP adherence support8 (4.8)
    Missing3 (1.8)
    Would you recommend using SMS text messaging as a support strategy for persons using PrEP?
    Yes134 (80.2)
    No18 (10.8)
    Not sure14 (8.4)
    Missing1 (0.6)
    What did you think about the frequency of the weekly messages?
    Too frequent (too many messages)9 (5.4)
    Adequate134 (80.2)
    Insufficient (very few messages)22 (13.2)
    Missing2 (1.2)
    Did you have any problems sending or receiving SMS text messages during the study?
    Yes38 (22.8)
    No127 (76.0)
    Missing2 (1.2)
     If yes, please describe (N=38)
    I ran out of prepaid credit8 (21.1)
    I lost my phone4 (10.5)
    My phone was stolen5 (13.2)
    I did not have access to my phone4 (10.5)
    Other13 (34.2)
    Missing4 (10.5)
    How many times did you seek support from the study site staff using SMS text message?
    Never144 (86.2)
    Once16 (9.6)
    Twice3 (1.8)
    3 or more times0 (0.0)
    Missing4 (2.4)
    Would you prefer to receive support messages via email rather than SMS text messaging?
    Yes19 (11.4)
    No140 (83.8)
    Not sure5 (3.0)
    Missing3 (1.8)

    aPrEP: pre-exposure prophylaxis.


    Principal Findings

    PrEP Brasil SMS substudy was the first effort to develop a mHealth intervention to improve oral PrEP adherence among MSM and transgender women in Latin America. Our results show that weekly SMS text messages were highly acceptable to support PrEP use, but they were not effective in increasing adequate PrEP adherence at week 48 among MSM and transgender women in Brazil. This could be partially explained by the preference of WhatsApp over SMS text messages in the country, including among MSM and transgender women [21,31]. In fact, approximately 96% of the Brazilian population uses WhatsApp [32], and the platform is considered more accessible and cost-effective than traditional SMS text messaging [33]. However, SMS text messaging was effective in improving adequate PrEP adherence measured by MPR among young MSM. Adequate adherence by MPR means that the participant has received enough pills to take daily oral PrEP, being “covered” by PrEP pills during all days between the study visits. Adequate MPR also indicates engagement with the service, as participants returned for PrEP prescriptions on time. In this sense, our study indicates that SMS text messaging can be effective to increase PrEP coverage and persistence among young MSM.

    In a previous analysis conducted in the PrEP Brasil study, we found that SMS text messaging increased adequate PrEP adherence measured by TDF-DP levels among young participants [22]. Some differences may explain these different results. First, the current analysis included only those participants enrolled in the SMS substudy. As such, the lack of significant statistical difference may have occurred due to a lower sample size. Second, the current statistical analysis compared outcomes at the 48-week visit, while the prior considered adherence levels across all follow-up visits. Finally, in the current analysis, we evaluated adherence stratified for young participants self-identified as cisgender men, while in the previous analysis, we grouped together all youth (both cisgender men and transgender women).

    Efficacy of SMS text message reminders among young MSM in our study may be linked to their higher familiarity with technology and digital communication [34]. Younger individuals tend to be more engaged with mobile devices and more open to digital health interventions [35]. Youth may also be more used to receiving and responding to automated messages, increasing the chance that these messages will support PrEP use and service engagement. This suggests that tailoring adherence interventions to the preferred communication channels of different age groups could improve their effectiveness.

    Our results provide evidence that text message interventions should be used to improve adherence outcomes, such as PrEP coverage and persistence, among young MSM, a population group with lower adherence compared with older counterparts [14]. Youth-tailored multicomponent mHealth intervention could be developed considering the Brazilian context. For instance, PrEPmate, an mHealth intervention grounded in the information, motivation, and behavioral theory of behavior, increased PrEP adherence among young MSM and transgender women in the United States [36].

    Other studies evaluating reminder text messages to improve adherence have shown conflicting results across different populations and settings. Fuchs and colleagues [30] demonstrated that a weekly bidirectional SMS text messaging was feasible, highly acceptable, and efficacious to improve PrEP adherence. However, SMS text messaging reminders were ineffective in promoting PrEP adherence among MSM and transgender women in the United States [28] and cisgender women aged 18‐24 years in Kenya [37]. These conflicting findings underscore the importance of considering not only the structure of the intervention but also the sociocultural and technological context in which it is implemented. The frequency and familiarity of SMS text messaging usage differ widely across countries. In some settings—such as Brazil—alternative messaging platforms such as WhatsApp may be more prevalent and better received.

    Other interventions alone or combined should be evaluated among MSM and transgender women in Brazil, including text messaging reminders using WhatsApp or apps, alarms, video games, cognitive behavioral therapies, motivational interviewing and counseling, support groups, or forums and peer navigation [20]. Additionally, it is important to evaluate the content of these messages, as several studies indicate that participants prefer messages that go beyond simple reminders, offering more engaging and meaningful content and the optimal frequency of reminders [30,38-40].

    Although only daily oral PrEP was recommended in Brazil during the study conduction, event-driven oral PrEP (ED-PrEP) is now part of national guidelines [41]. ED-PrEP will affect how we interpret indirect adherence assessments (eg, pill counts or MPR) as decisions on PrEP regimen and PrEP pill taking will depend on individuals’ demands and choices based on HIV-perceived risk and sexual behavior. In this sense, adequate pill availability is essential for effective daily oral PrEP or ED-PrEP, and SMS text messaging can be a useful technology to prevent pill shortage.

    Strengths and Limitations

    The major strength of this study is the randomized clinical trial design with allocation concealment. The demographics and baseline characteristics of the study groups were well balanced, and there was no significant difference in sample characteristics between intervention arms and, as such, less affected by selection or sampling bias. Although this was not a blinded study, 2 main outcomes (TFV-DP level and MPR) are not liable to human interference [42,43]. In addition, this was a low-cost intervention as we could program the SMS text messaging platform to submit a large number of text messages to different mobile phone numbers simultaneously.

    This study has limitations. First, our analysis was cross-sectional and restricted to adherence measured at week 48, as dried blood spots specimens for TFV-DP levels were collected from all participants exclusively at this visit. Second, no imputation was performed, and no statistical correction, such as inverse probability weighting, was applied to address potential bias due to loss to follow-up. However, it is worth noting that, given the high retention rate and the use of a single standardized time point, potential bias from missing data is likely to be limited. Third, we did not perform an analysis of the main outcomes among those who answered the messages. However, responding to SMS text messages remained relatively stable over the 48 weeks, with values varying slightly around 70%, suggesting consistent exposure and passive engagement with the intervention (Figure 3). Fourth, we did not capture participant engagement behavior, such as response latency, SMS text message read rate, or interaction dynamics over time. Fifth, self-reported adherence is subjected to recall, response, or social desirability bias [42,43]. Sixth, our study was conducted in 3 sites in Rio de Janeiro and São Paulo and thus cannot be generalized to all Brazilian MSM and transgender women. Seventh, only 6% of the overall sample was composed of transgender women. Finally, other apps designed to support medication adherence are available in Brazil, which could have interfered in our analysis.

    Conclusions

    Weekly SMS text message reminders successfully improved PrEP adherence among young MSM in Brazil. Future interventions should consider leveraging more widely adopted mHealth tools, such as WhatsApp or dedicated adherence apps, to better support PrEP use among MSM and transgender women in Brazil.

    Acknowledgments

    PrEP Brasil was sponsored by the Brazilian Ministry of Health, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Secretaria de Vigilância em Saúde, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, and Fundação de Amparo à Pesquisa do Estado de São Paulo. Gilead Sciences donated the study drug and covered costs for drug assessment. BG was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq#313265/2023‐2) and the Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ#E.26/200.946/2022). TST was supported by CNPq (311871/2021‐6) and FAPERJ (E-26/201.270/2022).

    Data Availability

    A complete deidentified dataset sufficient to reproduce the primary study findings will be made available on request to the corresponding author, following approval of a concept sheet summarizing the analyses to be done.

    Authors' Contributions

    BG, VGV, BH, and RIM contributed to conceptualization; RIM and ICL contributed to data curation; RIM, ICL, and MC led the formal analysis; BG contributed to the funding acquisition; LMSM, TST, LAF, JVM, and BH did the investigation; RIM, ICL, and MC contributed to methodology; BH and LAF led the project administration; RIM contributed to resources software; BH, JVM, BG, and VGV did supervision; LMSM and TST contributed to validation; RIM, ICL, and MC contributed to visualization; LMSM and TST contributed to writing—original draft; and RIM, ICL, MC, BH, LAF, DC, CC, EMJ, MSTS, JVM, BG, and VGV contributed to writing—review and editing.

    Conflicts of Interest

    None declared.

    Checklist 1

    CONSORT-EHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth) checklist.

    PDF File, 1220 KB
    1. Korenromp EL, Sabin K, Stover J, et al. New HIV infections among key populations and their partners in 2010 and 2022, by world region: a multisources estimation. J Acquir Immune Defic Syndr. 2024;95(1S):e34-e45. [CrossRef]
    2. Fact sheet—Latin America. UNAIDS. 2024. URL: https://www.unaids.org/en/resources/documents/2024/2024-unaids-global-aids-update-latin-america [Accessed 2024-04-11]
    3. Boletim Epidemiológico 2024. Brasil, Ministério da Saúde. 2024. URL: https:/​/www.​gov.br/​aids/​pt-br/​central-de-conteudo/​boletins-epidemiologicos/​2024/​boletim_hiv_aids_2024e.pdf/​view [Accessed 2025-05-02]
    4. Coelho LE, Torres TS, Veloso VG, et al. The prevalence of HIV among men who have sex with men (MSM) and young MSM in Latin America and the Caribbean: a systematic review. AIDS Behav. Oct 2021;25(10):3223-3237. [CrossRef] [Medline]
    5. Torres TS, Teixeira SLM, Hoagland B, et al. Recent HIV infection and annualized HIV incidence rates among sexual and gender minorities in Brazil and Peru (ImPrEP seroincidence study): a cross-sectional, multicenter study. Lancet Reg Health Am. Dec 2023;28:100642. [CrossRef] [Medline]
    6. Jalil CM, Jalil EM, Hoagland B, et al. The rising tide of HIV among young men who have sex with men in Brazil: insights from the Conectad@s study. Lancet Reg Health Am. Aug 2024;36:100798. [CrossRef] [Medline]
    7. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. Dec 30, 2010;363(27):2587-2599. [CrossRef]
    8. McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. Jan 2016;387(10013):53-60. [CrossRef]
    9. Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. Dec 3, 2015;373(23):2237-2246. [CrossRef] [Medline]
    10. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. Aug 2, 2012;367(5):423-434. [CrossRef]
    11. Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. Sep 12, 2012;4(151):151ra125. [CrossRef] [Medline]
    12. Liu AY, Yang Q, Huang Y, et al. Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP). PLoS One. 2014;9(1):e83736. [CrossRef]
    13. Grant RM, Anderson PL, McMahan V, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect Dis. Sep 2014;14(9):820-829. [CrossRef] [Medline]
    14. Veloso VG, Cáceres CF, Hoagland B, et al. Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study. Lancet HIV. Feb 2023;10(2):e84-e96. [CrossRef] [Medline]
    15. Konda KA, Torres TS, Mariño G, et al. Factors associated with long-term HIV pre-exposure prophylaxis engagement and adherence among transgender women in Brazil, Mexico and Peru: results from the ImPrEP study. J Int AIDS Soc. Oct 2022;25(Suppl 5):e25974. [CrossRef] [Medline]
    16. Miller G. The smartphone psychology manifesto. Perspect Psychol Sci. May 2012;7(3):221-237. [CrossRef] [Medline]
    17. Sun S, Simonsson O, McGarvey S, Torous J, Goldberg SB. Mobile phone interventions to improve health outcomes among patients with chronic diseases: an umbrella review and evidence synthesis from 34 meta-analyses. Lancet Digit Health. Nov 2024;6(11):e857-e870. [CrossRef] [Medline]
    18. da Costa TM, Barbosa BJP, Gomes e Costa DA, et al. Results of a randomized controlled trial to assess the effects of a mobile SMS-based intervention on treatment adherence in HIV/AIDS-infected Brazilian women and impressions and satisfaction with respect to incoming messages. Int J Med Inform. Apr 2012;81(4):257-269. [CrossRef] [Medline]
    19. Sullivan PS, Driggers R, Stekler JD, et al. Usability and acceptability of a mobile comprehensive HIV prevention app for men who have sex with men: a pilot study. JMIR Mhealth Uhealth. Mar 9, 2017;5(3):e26. [CrossRef] [Medline]
    20. Garcia C, Rehman N, Matos-Silva J, et al. Interventions to improve adherence to oral pre-exposure prophylaxis: a systematic review and network meta-analysis. AIDS Behav. Aug 2024;28(8):2534-2546. [CrossRef] [Medline]
    21. Castanheira D, Pereira CR, Jalil CM, et al. Young men who have sex with men and digital technologies for HIV prevention and care: qualitative findings from the conectad@s study. Cult Health Sex. Dec 3, 2024:1-16. [CrossRef]
    22. Grinsztejn B, Hoagland B, Moreira RI, et al. Retention, engagement, and adherence to pre-exposure prophylaxis for men who have sex with men and transgender women in PrEP Brasil: 48 week results of a demonstration study. Lancet HIV. Mar 2018;5(3):e136-e145. [CrossRef] [Medline]
    23. Hoagland B, De Boni RB, Moreira RI, et al. Awareness and willingness to use pre-exposure prophylaxis (PrEP) among men who have sex with men and transgender women in Brazil. AIDS Behav. May 2017;21(5):1278-1287. [CrossRef] [Medline]
    24. Marins LMS, Torres TS, Leite IDC, et al. Performance of HIV pre-exposure prophylaxis indirect adherence measures among men who have sex with men and transgender women: results from the PrEP Brasil Study. PLoS One. 2019;14(8):e0221281. [CrossRef] [Medline]
    25. Hoagland B, Moreira RI, De Boni RB, et al. High pre-exposure prophylaxis uptake and early adherence among men who have sex with men and transgender women at risk for HIV Infection: the PrEP Brasil demonstration project. J Int AIDS Soc. Apr 6, 2017;20(1):21472. [CrossRef] [Medline]
    26. Monteiro Spindola Marins L, Silva Torres T, Luz PM, et al. Factors associated with self-reported adherence to daily oral pre-exposure prophylaxis among men who have sex with man and transgender women: PrEP Brasil study. Int J STD AIDS. Nov 2021;32(13):1231-1241. [CrossRef] [Medline]
    27. Muchomba FM, Gearing RE, Simoni JM, El-Bassel N. State of the science of adherence in pre-exposure prophylaxis and microbicide trials. J Acquir Immune Defic Syndr. 2012;61(4):490-498. [CrossRef]
    28. Moore DJ, Jain S, Dubé MP, et al. Randomized controlled trial of daily text messages to support adherence to preexposure prophylaxis in individuals at risk for human immunodeficiency virus: the TAPIR Study. Clin Infect Dis. May 2, 2018;66(10):1566-1572. [CrossRef] [Medline]
    29. Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet. Nov 27, 2010;376(9755):1838-1845. [CrossRef] [Medline]
    30. Fuchs JD, Stojanovski K, Vittinghoff E, et al. A mobile health strategy to support adherence to antiretroviral preexposure prophylaxis. AIDS Patient Care STDS. Mar 2018;32(3):104-111. [CrossRef] [Medline]
    31. Pereira AAC, Destro JR, Picinin Bernuci M, Garcia LF, Rodrigues Lucena TF. Effects of a WhatsApp-delivered education intervention to enhance breast cancer knowledge in women: mixed-methods study. JMIR Mhealth Uhealth. Jul 21, 2020;8(7):e17430. [CrossRef]
    32. Rossini P, Baptista ÉA, Veiga de Oliveira V, Stromer-Galley J. Digital media landscape in Brazil: political (mis)information and participation on Facebook and WhatsApp. J Quant Description Digit Media. 2021;1:1-27. [CrossRef]
    33. Saboia F. The rise of WhatsApp in Brazil is about more than just messaging. Harvard Business Review. 2016. URL: https://hbr.org/2016/04/the-rise-of-whatsapp-in-brazil-is-about-more-than-just-messaging [Accessed 2024-01-17]
    34. Coordenação de Pesquisas por Amostra de Domicílios. Acesso à internet e à televisão e posse de telefone móvel celular para uso pessoal 2022 [Coordination of Household Sample Surveys. Access to the internet and television and ownership of mobile phones for personal use 2022]. In: Pesquisa Nacional Por Amostra de Domicílios Contínua (PNAD) [National Continuous Household Sample Survey (PNAD)]. IBGE—Brazilian Institute of Geography and Statistics; 2023.
    35. Feroz AS, Ali NA, Khoja A, Asad A, Saleem S. Using mobile phones to improve young people sexual and reproductive health in low and middle-income countries: a systematic review to identify barriers, facilitators, and range of mHealth solutions. Reprod Health. Jan 16, 2021;18(1):9. [CrossRef] [Medline]
    36. Liu AY, Vittinghoff E, von Felten P, et al. Randomized controlled trial of a mobile health intervention to promote retention and adherence to preexposure prophylaxis among young people at risk for human immunodeficiency virus: the EPIC Study. Clin Infect Dis. May 30, 2019;68(12):2010-2017. [CrossRef] [Medline]
    37. Haberer JE, Bukusi EA, Mugo NR, et al. Effect of SMS reminders on PrEP adherence in young Kenyan women (MPYA study): a randomised controlled trial. Lancet HIV. Mar 2021;8(3):e130-e137. [CrossRef] [Medline]
    38. Cruz MC, Cota VL, Lincoln L, de JA, Decotelli PV. Análise da implementação das estratégias de comunicação para as ações de testagem e sua vinculação ao tratamento de HIV/AIDS em homens que fazem sexo com homens em curitiba [analysis of the implementation of communication strategies for testing initiatives and their link to HIV/AIDS treatment among men who have sex with men in curitiba.]. 2021:665-679. URL: https://www.reciis.icict.fiocruz.br/index.php/reciis/article/view/2327 [Accessed 2025-07-15]
    39. Sullivan PS, Stephenson R, Hirshfield S, et al. Behavioral efficacy of a sexual health mobile app for men who have sex with men: randomized controlled trial of mobile messaging for men. J Med Internet Res. Feb 2, 2022;24(2):e34574. [CrossRef] [Medline]
    40. Giovenco D, Muessig KE, Horvitz C, et al. Adapting technology-based HIV prevention and care interventions for youth: lessons learned across five U.S. Adolescent Trials Network studies. Mhealth. 2021;7:21. [CrossRef] [Medline]
    41. Protocolo clínico e diretrizes terapêuticas para profilaxia pré-exposição à infecção pelo HIV. Brasil, Ministério da Saúde. 2025. URL: https:/​/www.​gov.br/​aids/​pt-br/​central-de-conteudo/​pcdts/​protocolo-clinico-e-diretrizes-terapeuticas-para-profilaxia-pre-exposicao-prep-oral-a-infeccao-pelo-hiv.pdf/​view [Accessed 2025-07-08]
    42. Haberer JE, Bangsberg DR, Baeten JM, et al. Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm. AIDS. Jul 17, 2015;29(11):1277-1285. [CrossRef] [Medline]
    43. Berg KM, Arnsten JH. Practical and conceptual challenges in measuring antiretroviral adherence. J Acquir Immune Defic Syndr. Dec 1, 2006;43(Suppl 1):S79-S87. [CrossRef] [Medline]

    ‎
    CONSORT-EHEALTH: Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth
    ED-PrEP: event-driven oral PrEP
    mHealth: mobile health
    MPR: medication possession ratio
    MSM: men who have sex with men
    PrEP: pre-exposure prophylaxis
    SOC: standard of care
    TFV-DP: tenofovir-diphosphate

    Edited by Javad Sarvestan; submitted 08.02.25; peer-reviewed by Diana Zeballos, Thérèse Bernier; final revised version received 20.05.25; accepted 21.05.25; published 18.07.25.

    Copyright

    © Luana Monteiro Spindola Marins, Thiago Silva Torres, Ronaldo Ismerio Moreira, Iuri Costa Leite, Marcelo Cunha, Brenda Hoagland, Lucilene Araujo Freitas, Debora Castanheira, Carolina Coutinho, Emilia Moreira Jalil, Mayara Secco Torres Silva, Jose Valdez Madruga, Beatriz Grinsztejn, Valdilea Gonçalves Veloso. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.7.2025.

    This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research (ISSN 1438-8871), is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.