Rachel Mukora

Background: Digital Adherence Technologies (DATs) are being investigated for use in many countries. In this study we evaluated the cost-effectiveness of a technology-enabled Differentiated Care Approach (DCA), where a medication monitor (Wisepill evriMED 1000 device) provided daily reminders and identified missed doses to guide SMS, phone call, and home visit interventions within the TB Monitoring Adherence to Treatment Endpoints (TB MATE) cluster-randomised trial in South Africa. Methods: We conducted a cost-effectiveness analysis from a societal perspective in one intervention clinic and one standard-of-care (SoC) clinic in each of three selected provinces between June 2019 and August 2020. Health system costs were collected using a bottom-up activity-based costing approach involving time and motion studies. People with Tuberculosis (PWTB) were interviewed on costs related to accessing the intervention. The primary efficacy outcome used in the trial was proportion of patients with ≥ 80% adherence, measured using medication monitor opening as a proxy for adherence. Unit costs were calculated as cost per patient treated for TB while incremental cost-effectiveness ratio (ICER) was calculated as cost per additional adherent PWTB. Results: From a total of 2757 enrolled (62% male, median age 36 years IQR (27–45 years), adherence data was available for 1306 PWTB in the intervention arm and 1278 PWTB in the SoC arm, where effectiveness was 81% and 50.8% in the intervention and SoC arms respectively. The total cost per patient treated for TB was $103.93-$199.87 (intervention) and $44.89 - $131.22 (SoC), resulting in a societal incremental cost of $49.73 (mean). Patient costs were $38.98 - $117.94 (intervention) and $35.92-$91.94 (SoC) per patient with indirect costs (foregone income) contributing to a large proportion of total costs at three intervention (56.7% − 69.8%) and two SoC (69% and 77.4%) clinics. The ICER of achieving an additional adherent PWTB was $166.33. Conclusion: Medication monitors and DCA can be considered a cost-effective option for investment and scale-up if we reduce health systems costs.

Background: Inadequate adherence to tuberculosis (TB) treatment increases the risk of treatment failure and recurrence. Identifying factors contributing to poor adherence could refine targeting strategies and optimize resource distribution. We examined specific individual-level factors for TB treatment adherence among adults with drug-sensitive TB, including HIV status, antiretroviral therapy, time to access clinical care, and perceived stigma. Methods: Data are from the “TB Mate” cluster-randomized trial, which evaluated a TB treatment adherence intervention across 18 public health clinics in South Africa (PACTR201902681157721). Treatment adherence was measured using smart pillboxes, with pillbox opening recorded as a proxy for the dose taken. Adults in the control group, utilizing the pillbox in silent mode, were included in this analysis. We used logistic regression to model poor adherence (< 80% pillbox engagement), and negative binomial regression to model adherence as a count of pillbox engagement. Directed acyclic graphs informed confounder selection in the models. Results: Among 1,213 participants (nine clinics) in the control group, 61.2% (742) were male, the median age was 36 years, 63% (769) were living with HIV, with 66% (507/769) on antiretroviral therapy. The median time to access clinical care was 127 min and 95% (1151/1213) reported no perceived stigmatization upon starting TB treatment. Overall 51% (614) exhibited adherence below 80%, with a geometric mean pillbox engagement of 59.6%. Living with HIV was associated with poor adherence to TB treatment, with an adjusted odds ratio of 1.68 (95% confidence interval [CI] 1.27–2.22) for < 80% adherence and an adjusted rate ratio of 0.90 (0.83–0.97) for pillbox engagement, compared to being HIV-negative. Antiretroviral therapy, time to clinical care access, and perceived stigma showed no association with either measure of adherence. Conclusions: The low adherence underscores the necessity for TB treatment support interventions, particularly among those living with HIV.

Introduction: Voluntary medical male circumcision (VMMC) clients are required to attend multiple post-operative follow-up visits in South Africa. However, with demonstrated VMMC safety, stretched clinic staff in SA may conduct more than 400,000 unnecessary reviews for males without complications, annually. Embedded into a randomized controlled trial (RCT) to test safety of two-way, text-based (2wT) follow-up as compared to routine in-person visits among adult clients, the objective of this study was to compare 2wT and routine post-VMMC care costs in rural and urban South African settings. Methods: Activity-based costing (ABC) estimated the costs of post-VMMC care, including counselling, follow-ups, and tracing in $US dollars. Transportation for VMMC and follow-up was provided for rural clients in outreach settings but not for urban clients in static sites. Data were collected from National Department of Health VMMC forms, RCT databases, and time-and-motion surveys. Sensitivity analysis presents different follow-up scenarios. We hypothesized that 2wT would save per-client costs overall, with higher savings in rural settings. Results: VMMC program costs were estimated from 1,084 RCT clients: 537 in routine care and 547 in 2wT. On average, 2wT saved $3.56 per client as compared to routine care. By location, 2wT saved $7.73 per rural client and increased urban costs by $0.59 per client. 2wT would save $2.16 and $7.02 in follow-up program costs if men attended one or two post-VMMC visits, respectively. Conclusion: Quality 2wT follow-up care reduces overall post-VMMC care costs by supporting most men to heal at home while triaging clients with potential complications to timely, in-person care. 2wT saves more in rural areas where 2wT offsets transportation costs. Minimal additional 2wT costs in urban areas reflect high care quality and client engagement, a worthy investment for improved VMMC service delivery. 2wT scale-up in South Africa could significantly reduce overall VMMC costs while maintaining service quality.

Background: The introduction of digital adherence technologies (DATs) such as medication monitors in tuberculosis (TB) programmes supports treatment adherence among people with tuberculosis (PWTB). We evaluated the acceptability of using medication monitors (Wisepill evriMED) prompting a stepwise differentiated care approach (DCA), involving short message service (SMS), phone calls, home visits and motivational counselling, among PWTB in South Africa. Methods: We conducted 62 in-depth interviews with participants in local languages across three provinces (January—October 2020), purposively selected by treatment month, adherence history and gender. Interviews were audio recorded, transcribed verbatim and translated. Using a deductive approach and the Theoretical Framework for Acceptability (TFA), we explored acceptability across the sample attributes. Results: PWTB across adherence histories showed a positive attitude to using the evriMED device and receiving the DCA support. PWTB described the SMS reminders and phone calls as effective reminders, though home visits were less acceptable, due to perceived stigma. Despite willingness to participate in the intervention, the large size of the monitor and sound of the alarm drew attention, potentially causing embarrassment and stigma. Due to perceived stigma, some PWTB adapted the intervention by leaving the monitor at home after removing the pills to ensure that someone else tracked usage, while the PWTB used alternative reminders such as cell phones to take their medication. Conclusion: Although PWTB showed a positive attitude towards the intervention, perceived stigma contributed to participants adapting their lifestyle to meet treatment adherence requirements without using the monitor. However, the medication monitor was a tool that seemed to prompt this personal change in behaviour. Achieving people-centered TB care, including the introduction of DATs, will require that TB programmes incorporate PWTB insights to maximize their use and effectiveness.

Objectives The tuberculosis (TB) MATE study evaluated whether a differentiated care approach (DCA) based on tablet-taking data from Wisepill evriMED digital adherence technology could improve TB treatment adherence. The DCA entailed a stepwise increase in adherence support starting from short message service (SMS) to phone calls, followed by home visits and motivational counselling. We explored feasibility of this approach with providers in implementing clinics. Design Between June 2020 and February 2021, in-depth interviews were conducted in the provider’s preferred language, audiorecorded, transcribed verbatim and translated. The interview guide included three categories: feasibility, system-level challenges and sustainability of the intervention. We assessed saturation and used thematic analysis. Setting Primary healthcare clinics in three provinces of South Africa. Participants We conducted 25 interviews with 18 staff and 7 stakeholders. Results Three major themes emerged: First, providers were supportive of the intervention being integrated into the TB programme and were eager to be trained on the device as it helped to monitor treatment adherence. Second, there were challenges in the adoption system such as shortage of human resources which could serve as a barrier to information provision once the intervention is scaled up. Healthcare workers reported that some patients received incorrect SMS’s due to delays in the system that contributed to distrust. Third, DCA was considered as a key aspect of the intervention by some staff and stakeholders since it allowed for support based on individual needs. Conclusions It was feasible to monitor TB treatment adherence using the evriMED device and DCA. To ensure successful scale-up of the adherence support system, emphasis will need to be placed on ensuring that the device and the network operate optimally and continued support on adhering to treatment which will enable people with TB to take ownership of their treatment journey and help overcome TB-related stigma. Trial registration number Pan African Trial Registry PACTR201902681157721.

Introduction Voluntary medical male circumcision (VMMC) clients are required to attend multiple post-operative follow-up visits in South Africa (SA). However, up to 98% of VMMC clients heal without adverse events (AEs). With demonstrated VMMC safety across global programs, stretched clinic staff in SA may conduct more than 400,000 unnecessary reviews for males without complications per year. As part of a randomized controlled trial (RCT) to test two-way texting (2wT) follow-up as compared to routine, in-person visits for adult VMMC clients, the objective of this study was to compare costs of 2wT-based telehealth to routine post-VMMC care in both rural and urban SA settings. Methods We used an activity-based costing (ABC) approach to estimate the costs in post-VMMC care, including counselling, follow-ups, and tracing activities. All costs were estimated in $US dollars for both 2wT and routine care to test the hypotheses that 2wT follow-up would result in per-client cost savings. Data were collected from routine National Department of Health VMMC forms, the RCT database, and time-and-motion surveys. Sensitivity analysis presents different scale-up scenarios. Results We included 1,084 clients: 537 in routine care and 547 in 2wT. Average client follow-up cost is $6.48 for routine care and $4.25 for 2wT. 2wT saved costs in both rural and urban locations. Average savings of $2.23 was greater in rural ($1.61) than urban areas ($0.62). 2wT would save $0.88, $2.23, and $4.93, respectively, if: men attended one visit; men attended visits in similar proportions to that observed in the RCT; and men attended both visits. Conclusion 2wT reduces post-VMMC care costs by supporting most men to heal at home while using telehealth to triage clients with potential AEs to timely, in-person care. 2wT savings are higher in rural areas. Scale-up of 2wT-based follow-up could significantly reduce overall VMMC costs while maintaining service quality.

Background: Studies estimate that circumcising men between the ages of 20–30 years who have exhibited previous risky sexual behaviour could reduce overall HIV prevalence. Demand creation strategies for medical male circumcision (MMC) targeting men in this age group may significantly impact these prevalence rates. Objectives: The objective of this study is to evaluate the cost-effectiveness and cost-benefit of an implementation science, pre-post study designed to increase the uptake of male circumcision for ages 25–49 at a fixed MMC clinic located in Gauteng Province, South Africa. Methods: A health care provider perspective was utilised to collect all costs. Costs were compared between the standard care scenario of routine outreach strategies and a full intervention strategy. Cost-effectiveness was measured as cost per mature man enrolled and cost per mature man circumcised. A cost-benefit analysis was employed by using the Bernoulli model to estimate the cases of HIV averted due to medical male circumcision (MMC), and subsequently translated to averted medical costs. Results: In the 2015 intervention, the cost of the intervention was $9445 for 722 men. The total HIV treatment costs averted due to the intervention were $542,491 from a public care model and $378,073 from a private care model. The benefit-cost ratio was 57.44 for the public care model and 40.03 for the private care model. The net savings of the intervention were $533,046 or $368,628 - depending on treatment in a public or private setting. Conclusions: The intervention was cost-effective compared to similar MMC demand interventions and led to statistically significant cost savings per individual enrolled.

Background: South Africa has achieved drug-susceptible TB (DS-TB) treatment success of only 77% among people with new and previously treated TB. Alternative approaches are required to improve medication adherence and treatment completion to limit transmission, TB relapse and the development of resistance. This study aims to implement and evaluate the use of adherence medication monitors (Wisepill evriMED 1000) with a differentiated response to patient care, among DS-TB patients in three provinces of South Africa. Methods: In total, 18 public health clinics across three provinces were selected. Clinics were randomised to intervention or standard of care clinics. In each clinic, approximately 145 DS-TB patients are being enrolled to reach a total of 2610. All patients have their daily adherence monitored using medication monitors. In the intervention arm, patients are receiving medication monitor reminders and differentiated care in response to adherence data. This weekly review of daily real-time monitoring will be undertaken from a central database. The differentiated care model includes automated SMS reminders with a missed dose, research staff-initiated phone call to the patient with a second or third missed dose, a home visit if four or more doses are missed, and motivational counselling if four or more doses are missed repeatedly. Fidelity of the intervention will be measured through process evaluation. Patients in control clinics will receive medication monitors for adherence tracking, standard of care TB education, and normal clinic follow-up procedures. The primary outcome is the proportion of patients by arm with >80% adherence, as measured by the medication monitor. The feasibility and acceptability of the intervention will be assessed by in-depth interviews with patients, stakeholders, and study staff. A cost effectiveness analysis of the intervention and standard of care clinics will be conducted. Significance: This trial will provide evidence for the use of an intervention, including medication monitors and differentiated care package, to improve adherence to TB treatment. Improved adherence should also improve TB treatment completion rates, thus reducing loss to follow-up rates, and TB relapse among people with TB. The intervention is intended to ultimately improve overall TB control and reduce TB transmission in South Africa. Trial registration: Pan African Trial Registry PACTR201902681157721. Registered on 11 February 2019.

INTRODUCTION: The World Health Organization recommends point-of-care (POC) lateral flow urine lipoarabinomannan (LF-LAM) for tuberculosis (TB) diagnosis in selected human immunodeficiency virus (HIV) positive people. South Africa had 438 000 new TB episodes in 2016, 58.9% of which were contributed by HIV-positive people. LF-LAM is being considered for scale-up in South Africa. METHODS: We estimated the costs of using LF-LAM in HIV-positive adults with CD4 counts  150 cells/μl enrolled in the TB Fast Track Trial in South Africa. We also estimated costs of POC haemoglobin (Hb), as this was used in the study algorithm. Data on clinic-level (10 intervention clinics) and above-clinic-level costs were collected. RESULTS: A total of 1307 LF-LAM tests were performed at 10 clinics over 24 months. The mean clinic-level costs were US$12.80 per patient for LF-LAM and POC Hb; LF-LAM costs were US$11.49 per patient. The mean above-clinic-level unit costs for LF-LAM were US$12.06 for clinic preparation, training, coordination and mentoring. The mean total cost of LF-LAM was US$23.55 per patient. CONCLUSION: At clinic level, the cost of LF-LAM was comparable to other TB diagnostics in South Africa. It is important to consider above-clinic-level costs for POC tests, as these may be required to support roll-out and ensure successful implementation.