The Effectiveness of SMS in Improving Antiretroviral Medication Adherence Among Adolescents Living With HIV in Nigeria
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional

Summary: 
      The non-maintenance of ART adherence is a major barrier to the achievement of optimal
      treatment outcomes among adolescents living with HIV. ART adherence is a challenge among
      adolescents living with HIV because of lack of appropriate information, their unique
      emotional state and lifestyles but the most commonly quoted challenge to adherence is
      forgetting to take antiretroviral drugs. There is evidence to suggest that short message
      service (SMS) reminder- interventions may enhance drug compliance among adolescents living
      with other chronic diseases such as asthma and diabetes. Available literature underscores the
      need for randomized controlled trials (RCTs) of effective interventions to promote ART
      adherence among adolescents with HIV.

      The aim of this study is to evaluate the feasibility, acceptability, and efficacy of
      interactive and tailored SMS reminders on ART adherence among adolescents (15-19 years)
      living with HIV in Ogun State, Nigeria. The study hypothesizes that the use of personal
      mobile phones and SMS reminders for the improvement of ART adherence among adolescents living
      with HIV are feasible, acceptable, and effective.

      A single-blind, parallel-design (ratio 1:1), and multi-center RCT of 230 adolescent living
      with HIV who are non-adherent to medications will be conducted over a one-year period in
      Southwest Nigeria. All the participants will receive routine adherence counseling during
      clinic visits and one SMS reminder each for follow-up appointments 48 hours and 24 hours
      before the follow-up visit date. The intervention group will also receive daily ART adherence
      reminder SMS. Participants will be assessed at baseline and during follow-up visits at 4, 8,
      12, 16 and 20 weeks after the baseline. Baseline assessment of participants will include
      socio-demographic characteristics; HIV/AIDS risk behaviour assessment, Alcohol and Drug abuse
      assessment, Client Satisfaction Survey, ART adherence assessment, CD4count and viral load
      assessments. ART adherence and client satisfaction will be assessed at each follow-up visit
      while CD4count and viral load assessments will be done at baseline and at 20th week.

      It is possible that tailored SMS reminders will mitigate the barrier of forgetfulness in
      ART-adherence and lead to improved drug compliance, viral suppression, and quality of life
      among adolescents living with HIV.
    

Detailed description: 
      BACKGROUND In Nigeria, approximately 3.2 million people were living with human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in Nigeria. Nigeria
      has about 196,000 adolescents (10-19 years) living with HIV with an estimated 17,000 new
      infections and 11,000 AIDS-related deaths per year in the age group. Adolescents aged 15 to
      19 years constitute 8.8% of Nigeria's over 173 million people and have an HIV prevalence rate
      of 2.9%.

      Non-adherence to antiretroviral therapy (ART) increases the risk of non-suppression of HIV,
      secondary HIV transmission, and development of drug resistance; it has a negative impact on
      treatment outcomes, leads to decreased survival and worsened quality of life. Adolescents on
      ART have lower viral suppression rates (49%) when compared with both adults and younger
      children (72.8% and 57%) and this is one of the most frequent causes of lower adherence to
      ART.

      The non-maintained ART adherence is a major barrier to the achievement of optimal treatment
      outcomes among adolescents living with HIV. ART adherence is a challenge among adolescents
      living with HIV because of lack of appropriate information, their unique emotional state and
      lifestyles. Religious, cultural, social and health services related factors have also been
      recognized as a source of non-adherence to ART treatment. Other known barriers to ART
      adherence include difficult dosing schedule, side effects, food restrictions and pill burden
      but the most commonly quoted challenge to adherence is forgetting to take antiretroviral
      drugs. Many strategies, including directly observed drug use, adherence counselling,
      telephone calls and reminder devices adopted to enhance ART adherence have turned out to be
      time-consuming, costly and intrusive.

      With over 148 million active mobile lines, short message service (SMS) has become a common
      means of communication in Nigeria. SMS is used commonly by teenagers, including those who are
      economically disadvantaged. SMS has been applied in a variety of healthcare setting because
      of its low-cost and convenient technology and has proved to be an effective tool for
      behavioural change interventions. There is evidence to suggest that SMS interventions may
      enhance drug compliance among adolescents living with other chronic diseases such as asthma
      and diabetes. An RCT showed that text-messaging system increased adherence to medication
      among adolescents by about 7%. While studies have evaluated the effectiveness of SMS
      reminders on ART adherence among PLHIV in some low-resource settings, to the best of our
      knowledge studies that evaluated SMS reminders for adolescents living with HIV have not yet
      been published. Indeed, a Cochrane systematic review of randomized controlled trials (RCTs)
      that assessed the effectiveness of SMS for improving ART adherence among people living with
      HIV infection identified the need of RCTs for this intervention among adolescents.

      Mobile technology communicates interventions to people in real-time and in their natural
      habitat. A review of the literature on SMS interventions for behavioural change in health
      care settings identified key characteristics for success such as interactivity and tailored
      messages.

      PROJECT OBJECTIVES Objective 1: To evaluate the efficacy of interactive and tailored SMS
      reminders on ART adherence among adolescents (15-19 years) living with HIV in Southwest,
      Nigeria.

      Objective 2: To assess the feasibility and acceptability of using personal mobile phones and
      interactive and tailored SMS reminders for the improvement of ART adherence among adolescents
      living with HIV in Southwest, Nigeria.

      Objective 3: To identify the predictors of ART non-adherence among adolescents (15-19 years)
      living with HIV in Southwest, Nigeria.

      STUDY HYPOTHESES

        1. Interactive and tailored SMS reminders are efficacious in the improvement of ART
           adherence among adolescents (15-19) years living with HIV.

        2. The use of personal mobile phones for the improvement of ART adherence among adolescents
           living with HIV is feasible and acceptable.

        3. ART adherence among adolescents is predicted by demographic, socioeconomic, and
           psychosocial factors.

      METHODOLOGY Study design and procedure This study is designed to have 80% power to detect a
      difference of 20%. When the proportion of adolescents who are adherent to ART was taken as
      49% (5), a sample size of 104 per group was obtained. The study will recruit 230 participants
      from the ART clinics in Southwest Nigeria into a randomized controlled trial (RCT).
      Convenience sampling method by which participants will be recruited on routine clinic visits
      across five (5) high patient-density ART sites will be used.

      For the purpose of this study, we defined poor adherence as self-reported < 95% adherence in
      the preceding one month using a validated visual analogue scale. Self-reported 95% adherence
      level is an ideal cut-off point because self-reported measures tend to exaggerate adherence
      and such high adherence level will minimize the occurrence of false-negatives.

      Initial eligibility screening and recruitment will be carried out by the primary caregivers
      using a checklist. Potential participants who meet the first four criteria will be presented
      with a visual analogue scale (VAS) labelled 0 to 100% at intervals of 5%. Eligible and
      willing participants will then be referred to the research assistants for a comprehensive
      informed consent process.

      Baseline activities

      At the baseline, the research assistants will give the volunteer participants a detailed
      explanation of the study, including its aim, duration, intervention and possible benefits.
      All the volunteers will be required to give a signed informed consent in a private room.
      Adolescents aged 15 to 19 years are thought to be relatively mature. According to a brief of
      AIDS regulations and Laws in Nigeria, children who are deemed mature in this context are
      capable of giving informed consent. Besides, based on evidence from South Africa and Lesotho,
      the WHO recommended that the legal age of consent for HIV testing and treatment should be 12
      years. The consenting volunteers will then be allocated unique identifiers that they will
      maintain throughout the course of the study. The contact details of the lead investigator
      will be made available to the participants so that he can be reached directly for any reason
      that is related to the study. Baseline data will be obtained in a private room by trained
      research assistants using structured interviewer-administered paper-based questionnaires over
      a period of about 40 minutes. The questionnaire will assess:

        1. socio-demographic variables.

        2. HIV/AIDS risk behaviour assessment: This will be done using the AIDS Risk Behavior
           Assessment (ARBA); a validated, adolescent-specific tool for the assessment of sexual
           behaviour, drug and alcohol use, and HIV-associated needle use. It assesses sexual
           behaviour over the previous 30 days and the previous three months.

        3. Alcohol and Drug abuse assessment: The Alcohol Use Disorders Identification Test (AUDIT)
           will be used to assess alcohol abuse. AUDIT, which was developed in 1982 by the World
           Health Organization, is a simple tool that is used to screen for and to identify people
           who are at risk of alcohol problems. The drug abuse screening test (DAST-20, adolescent
           version) will be used to screen for drug abuse. DAST is a validated scale that was
           designed to provide a brief, self-reported instrument for population screening, clinical
           case finding, and treatment evaluation research. It yields a quantitative index of the
           drug abuse consequences.

        4. Client Satisfaction Survey: A 22-item adaptation of the SERVQUAL tool will be used for
           this purpose. First published in 1988, the SERVQUAL is a multi-dimensional tool that
           assesses patients expected and perceived quality of services across five domains. Its
           use currently dominates research and industry for the assessment of quality of services
           and is well-validated in HIV service quality assessment.

        5. Adherence assessment: This will be done using the validated visual analogue scale
           (described above), monthly pill count, pharmacy records and the AIDS Clinical Trials
           Group (ACTG) adherence questionnaire. The research assistants will carry out pill counts
           and obtain the pharmacy records. Adherence assessment will be carried out at baseline
           and at every follow-up visit.

      Ten millilitres (10 ml) of blood samples will also be taken by laboratory scientists to
      measure the volunteers' CD4 cell count and HIV viral load. Sampling collection, handling and
      disposal will follow the standards and guidelines outlined by the WHO and PEPFAR. The
      participants' capability to operate mobile phones will be enhanced. The research assistants
      will work with participants to select from a list the most preferred SMS that will serve as a
      daily reminder of ART adherence. Each participant will select an SMS format that will serve
      as a reminder for follow-up visit reminders. In addition, the participants will also choose
      the preferred language and time for SMS reminders. The messages will be designed in such a
      way that they are sensitive and protect the privacy of the participants. The participants
      will be able to contact the lead investigator if they wish to change their chosen messages or
      if the services to their mobile phones are disrupted.

      Data Analysis The research assistants will code and enter the data obtained into Microsoft
      excel software in the CSV format. The data will be exported to the STATA version 15/SE for
      analyses. The data manager will fully review 5% (one in every twenty) questionnaire for
      errors. The data manager in conjunction with the investigators will be responsible for
      baseline, interim and final data analysis. The investigators, data manager, research
      assistants, counsellors and other project staff will be blinded throughout the study. After
      the scientific review has been completed and data collection has been completed, at the point
      of analysis, a list of participants' unique identifiers in two groups will be sent to the
      data analysts without specifying which the investigation or control group is. The blinding of
      the clinical database will finally be removed after final data analysis has been completed.

      Statistical Methods Intention-to-treat analysis will be carried out. Baseline characteristics
      will be compared using the chi-square test, rank-sum test, and independent t-test as
      appropriate. The independent t-test will be used to compare the means of ART adherence
      between the investigation and control groups after each follow-up visit in order to test if
      the intervention has any effect. The incidence proportion, incidence rate, relative risk,
      risk difference, and odds ratio will be used to measure the effect. Survival analysis will
      also be carried out to adjust for censoring (competing risk and loss to follow-up). Multiple
      regression analyses will be used to control for possible confounders. Subgroup analysis will
      also be undertaken in order to generate further hypotheses.

      The acceptability of the SMS will be accessed by the responses given by participants. The
      proportion of participants who find the method acceptable will be determined.

      The feasibility will be determined using the proportion of participants who are deemed to
      have completed the study (participate fully).

      The study will also assess client satisfaction and the possible effect of adherence on the
      mental health status of adolescents. Correlation and linear regression analyses will be used
      to determine the association between adherence (percent) and mental health status (GHQ 12
      measure).
    

Intervention name(s): Daily ART-adherence SMS reminder; Standard Adherence Counselling/Patient experience group chat
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Interactive and tailored SMS reminders that are acceptable to the participants to remind them to take their medications and to make clinic attendance.; All the participants will receive the standard adherence counselling by trained counsellors at each visit.
All participants will also be enlisted in a group chat on social media where they will discuss their experiences with the quality of HIV services rendered at their respective clinics. A specialist who will have very minimal involvement will give weekly feedback and counsel on how best to resolve prominent challenges.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A single-blind, parallel-design (ratio 1:1), and multi-centre RCT of 230 adolescent living with HIV who are non-adherent to medications will be conducted over a one-year period in Southwest Nigeria.
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Adherence; Adolescents; Antiretroviral therapy; HIV; Nigeria; Randomized controlled trial; Short message services