Protocol of a parallel group Randomized Control Trial (RCT) for Mobile-assisted Medication Adherence Support (Ma-MAS) intervention among Tuberculosis patients

Background Non-adherence to Tuberculosis (TB) medication is a serious threat to TB prevention and control programs, especially in resource-limited settings. The growth of the popularity of mobile phones provides opportunities to address non-adherence, by facilitating direct communication more frequently between healthcare providers and patients through SMS texts and voice phone calls. However, the existing evidence is inconsistent about the effect of SMS interventions on TB treatment adherence. Such interventions are also seldom developed based on appropriate theoretical foundations. Therefore, there is a reason to approach this problem more rigorously, by developing the intervention systematically with evidence-based theory and conducting the trial with strong measurement methods. Methods This study is a single-blind parallel-group design individual randomized control trial. A total of 186 participants (93 per group) will be individually randomized into one of the two groups with a 1:1 allocation ratio by a computer-generated algorithm. Group one (intervention) participants will receive daily SMS texts and weekly phone calls concerning their daily medication intake and medication refill clinic visit reminder and group two (control) participants will receive the same routine standard treatment care as the intervention group, but no SMS text and phone calls. All participants will be followed for two months of home-based self-administered medication during the continuation phases of the standard treatment period. Urine test for the presence of isoniazid (INH) drug metabolites in urine will be undertaken at the random point at the fourth and eighth weeks of intervention to measure medication adherence. Medication adherence will also be assessed by self-report measurements using the AIDS Clinical Trial Group adherence (ACTG) and Visual Analogue Scales (VAS) questionnaires, and clinic appointment attendance registration. Multivariable regression model analysis will be employed to assess the effect of the Ma-MAS intervention at a significance level of P-value < 0.05 with a 95% confidence interval. Discussion For this trial, a mobile-assisted medication adherence intervention will first be developed systematically based on the Medical Research Council framework using appropriate behavioural theory and evidence. The trial will then evaluate the effect of SMS texts and phone calls on TB medication adherence. Evidence generated from this trial will be highly valuable for policymakers, program managers, and healthcare providers working in Ethiopia and beyond. Trial registration The trial is registered in the Pan-Africa Clinical Trials Registry with trial number PACTR202002831201865.

School-level Barriers of Antiretroviral Therapy Adherence and Interventions to Overcome them Among Adolescents Living with HIV in Western Kenya: A Qualitative Study

Background: Adolescents in Kenya spend the majority of their time in a school environment. However, research to understand Antiretroviral Therapy (ART) adherence among adolescents living with HIV (ALWHIV) in school settings is sparse. Objective: To improve the design of appropriate interventions to better support this vulnerable population, the study aimed to explore school-related barriers to ART adherence experienced by ALWHIV. Methods: Qualitative data were utilized from a larger mixed-methods study on ALWHIV conducted at a major teaching and referral hospital in Kisumu, Kenya. Participants encompassed ALWHIV, their caregivers, teachers, and health care providers. Transcripts from a total of 24 in-depth interviews and five focus group discussions were analyzed in NVivo using a thematic approach. Results: Four themes emerged as key barriers in a school setting: negative experiences following HIV status self-disclosure, a strong desire for secrecy, restrictive school policies, and health education focused on sexual transmission of HIV. Participants suggested a range of potential interventions to better support ART adherence for ALWHIV, including coaching ALWHIV on disclosure strategies, promoting empathy among teachers and students, transition-preparing for ALWHIV, changing the narrative about HIV transmission in schools, providing water in schools, and introducing adherence support programs in schools, including the use of mobile technology. Conclusion: ALWHIV in Kenya experience numerous important challenges while trying to maintain optimal ART adherence in the school environment. Interventions that create supportive school settings are critical for better health outcomes among ALWHIV.

Improving Tuberculosis Treatment Adherence Support: The Case for Targeted Behavioral Interventions

Problem definition: Lack of patient adherence to treatment protocols is a main barrier to reducing the global disease burden of tuberculosis (TB). We study the operational design of a treatment adherence support (TAS) platform that requires patients to verify their treatment adherence on a daily basis. Academic/practical relevance: Experimental results on the effectiveness of TAS programs have been mixed; and rigorous research is needed on how to structure these motivational programs, particularly in resource-limited settings. Our analysis establishes that patient engagement can be increased by personal sponsor outreach and that patient behavior data can be used to identify at-risk patients for targeted outreach. Methodology: We partner with a TB TAS provider and use data from a completed randomized controlled trial. We use administrative variation in the timing of peer sponsor outreach to evaluate the impact of personal messages on subsequent patient verification behavior. We then develop a rolling-horizon machine learning (ML) framework to generate dynamic risk predictions for patients enrolled on the platform. Results: We find that, on average, sponsor outreach to patients increases the odds ratio of next-day treatment adherence verification by 35%. Furthermore, patients’ prior verification behavior can be used to accurately predict short-term (treatment adherence verification) and long-term (successful treatment completion) outcomes. These results allow the provider to target and implement behavioral interventions to at-risk patients. Managerial implications: Our results indicate that, compared with a benchmark policy, the TAS platform could reach the same number of at-risk patients with 6%–40% less capacity, or reach 2%–20% more at-risk patients with the same capacity, by using various ML-based prioritization policies that leverage patient engagement data. Personal sponsor outreach to all patients is likely to be very costly, so targeted TAS may substantially improve the cost-effectiveness of TAS programs.

The Development of a Smart Reminder System to Promote Adherence to Technology-Based Intervention and Assessment

The overarching aim of the National Institute on Aging funded Adherence Promotion with Person-centered Technology (APPT) Project is to promote adherence to technology-based solutions designed to enhance the early detection and treatment of cognitive decline. The goal is to build and evaluate adaptive, tailored, and integrated technology-based adherence support systems for mobile software platforms that assess and train cognitive skill. The symposium describes the various steps of the development process of the APPT smart adherence support system. N. Charness will present an overview of the APPT project, its aims, and the clinical trials designed to assess the effectiveness of the APPT smart reminder system compared to typical reminder systems. S. Chakraborty will present detailed analyses of past cognitive intervention data to inform understanding of who is likely at risk for poor adherence and how adherence lapses might be predicted in advance to provide just-in-time adherence support. D. Carr will present an exploration of motivating factors for participants to engage in research, and these motivations will be tapped to help develop motivational messages for the APPT adherence support system to be used in the two planned clinical trials. M. Dieciuc will provide additional insights into motivations for engaging in home-based cognitive assessment and training derived from a focus group study. Finally, S. Zhang will describe the results of an initial pilot study examining the effectiveness of motivational reminder messages that match vs. mismatch participants’ own motivations. All results inform the design of the APPT system to maximize adherence.

Aims of the Adherence Promotion With Person-Centered Technology (APPT) Project

The APPT project supports the early detection and treatment of age-related cognitive decline and dementia by 1) enhancing adherence to cognitive intervention and assessment protocols, 2) improving understanding of barriers to long-term adherence, and 3) developing algorithms for predicting and preventing adherence failures. Two randomized controlled trials will test an adaptive technology support system predicted to boost adherence to cognitive protocols over a period of six months within samples of older adults with and without cognitive impairment. These studies will provide insight into the benefits of adherence support, and individual difference factors that should shape the adherence protocol, informing the process of identifying individuals who would benefit from additional support and predicting and preventing extended adherence failures before they happen. These studies should improve early detection and treatment of cognitive decline, extend functional independence, and improve lives of those with cognitive impairment as well as the lives of their families.

Two decades (1998 to 2018) of collaborative human immunodeficiency virus clinical pharmacology capacity building in a resource constrained setting

While important advances have been made in the prevention and treatment of Human Immunodeficiency Virus (HIV) infection, limited expertise and resource constraints to effectively manage rollout of HIV programs often contribute to poor treatment outcomes in Sub-Saharan Africa. In 1998, the University of Zimbabwe (UZ) and the University at Buffalo, State University of New York (UB), developed a collaborative clinical pharmacology capacity building program in Zimbabwe to train the next generation of HIV researchers and support rollout of the national HIV program. The collaboration was funded by research and training grants that were competitively acquired through United States of America government funding mechanisms, between 1998 and 2016. Thirty-eight research fellows were trained and a specialty clinical pharmacology laboratory was established during this period. Knowledge and skills transfer were achieved through faculty and student exchange visits. Scientific dissemination output included sixty-two scholarly publications that influenced three national policies and provided development of guidelines for strategic leadership for an HIV infection—patient adherence support group. The clinical pharmacology capacity building program trained fellows that were subsequently incorporated into the national technical working group at the Ministry of Health and Child Care, who are responsible for optimizing HIV treatment guidelines in Zimbabwe. Despite serious economic challenges, consistent collaboration between UZ and UB strengthened UZ faculty scholarly capacity, retention of HIV clinical research workforce was achieved, and the program made additional contributions toward optimization of antiretroviral therapy in Zimbabwe.

Group counselling for adherence support among young people failing first-line antiretroviral therapy in Zimbabwe

Background: Sub-optimal adherence to antiretroviral therapy (ART) is reportedly worse amongst young people living with HIV (YPLHIV). Group adherence counselling can be useful to improve adherence.Objectives: We evaluated an enhanced adherence counselling group intervention (EACGI) amongst YPLHIV failing a non-nucleoside reverse transcriptase (NNRTI)-based first-line ART regimen.Method: This was a retrospective cohort study using routinely collected data of YPLHIV failing NNRTI-based first-line ART. Patients with confirmed virological failure were referred for EACGI, a 12-week curriculum of weekly, 1.5-h sessions accommodating 8–15 people per group. It aimed to facilitate readiness to switch to second-line ART and improve adherence through a mental health intervention. Viral loads of HIV were measured pre-EACGI; at baseline; 3, 6 and 12 months post switch.Results: Fifty-seven patients aged 13–25 years were invited to EACGI and followed for up to 48 weeks. Thirty-three (58%) patients attended at least four sessions, whilst 24 (42%) attended none. Amongst those who attended none, two (8%) were transferred out, three (13%) were lost to follow-up and two (8%) had died by week 48 of follow-up, whilst all who attended were still in care. By week 48, amongst patients still in care, 29%, 44% and 67% of those who attended no sessions, 4–9 and 10–12 sessions, respectively, had viral loads of 50 copies/mL.Conclusion: An EACGI is a promising intervention for YPLHIV failing ART prior to treatment switch, leading to improved adherence. This study’s findings support the need for further enquiry into rigorous, evidence-based multilevel adherence interventions that are acceptable and effective for YPLHIV.

Experiences with a violence and mental health safety protocol for a randomized controlled trial to support youth living with HIV

Background Safety protocols are an essential component of studies addressing violence and mental health but are rarely described in the published literature from Sub-Saharan Africa. We designed and implemented a safety protocol within Project YES! (Youth Engaging for Success), which enrolled 276 youth living with HIV (ages 15–24 years) in a randomized controlled trial of a peer-mentoring intervention across four HIV clinics in Ndola, Zambia. Methods Youth who reported severe violence and/or suicidal thoughts on research surveys or during meetings with youth peer mentors (YPM) were referred to designated healthcare providers (HCP). We explored experiences with the safety protocol using: a) monitoring data of referrals, and b) in-depth interviews with youth (n = 82), HCP (n = 10), YPM (n = 8), and staff (n = 6). Descriptive statistics were generated and thematic analysis of coded transcripts and written memos performed. Results Nearly half of youth enrolled (48% of females, 41% of males) were referred to a HCP at least once. The first referral was most often for sexual violence (35%) and/or suicidal ideation/depression (29%). All referred youth aged 15–17 years and over 80% of referred youth aged 18 + agreed to see a HCP. HCP referred 15% for additional services outside the clinic. Twenty-nine youth, all HCP, all YPM, and all staff interviewed discussed the safety protocol. Most youth felt “encouraged,” “helped,” “unburdened,” and “relieved” by their meetings with HCP; some expressed concerns about meeting with HCP. The safety protocol helped HCP recognize the need to integrate care for violence and mental health with medication adherence support. HCP, YPM, and study staff raised implementation challenges, including youth choosing not to open up to HCP, time and resource constraints, deficiencies in HCP training, and stigma and cultural norms inhibiting referrals outside the clinic for emotional trauma and mental health. Conclusions Implementing a safety protocol within an HIV clinic-based research study is possible and beneficial for youth and HCP alike. Implementation challenges underscore that HCP in Zambia work in over-stretched healthcare systems. Innovative strategies must address deficiencies in training and resources within HIV clinics and gaps in coordination across services to meet the overwhelming need for violence and mental health services among youth living with HIV.

Engaging with the private healthcare sector for the control of tuberculosis in India: cost and cost-effectiveness

BackgroundThe control of tuberculosis (TB) in India is complicated by the presence of a large, disorganised private sector where most patients first seek care. Following pilots in Mumbai and Patna (two major cities in India), an initiative known as the ‘Public–Private Interface Agency’ (PPIA) is now being expanded across the country. We aimed to estimate the cost-effectiveness of scaling up PPIA operations, in line with India’s National Strategic Plan for TB control.MethodsFocusing on Mumbai and Patna, we collected cost data from implementing organisations in both cities and combined this data with models of TB transmission dynamics. Estimating the cost per disability adjusted life years (DALY) averted between 2014 (the start of PPIA scale-up) and 2025, we assessed cost-effectiveness using two willingness-to-pay approaches: a WHO-CHOICE threshold based on per-capita economic productivity, and a more stringent threshold incorporating opportunity costs in the health system.FindingsA PPIA scaled up to ultimately reach 50% of privately treated TB patients in Mumbai and Patna would cost, respectively, US$228 (95% uncertainty interval (UI): 159 to 320) per DALY averted and US$564 (95% uncertainty interval (UI): 409 to 775) per DALY averted. In Mumbai, the PPIA would be cost-effective relative to all thresholds considered. In Patna, if focusing on adherence support, rather than on improved diagnosis, the PPIA would be cost-effective relative to all thresholds considered. These differences between sites arise from variations in the burden of drug resistance: among the services of a PPIA, improved diagnosis (including rapid tests with genotypic drug sensitivity testing) has greatest value in settings such as Mumbai, with a high burden of drug-resistant TB.ConclusionsTo accelerate decline in TB incidence, it is critical first to engage effectively with the private sector in India. Mechanisms such as the PPIA offer cost-effective ways of doing so, particularly when tailored to local settings.