Cost and Impact of Dried Blood Spot Versus Plasma Separation Card for Scale-up of Viral Load Testing in Resource-limited Settings.

BACKGROUND: Routine plasma viral load (VL) testing is recommended for monitoring human immunodeficiency virus-infected patients on antiretroviral therapy. In Zambia, VL scale-up is limited due to logistical obstacles around plasma specimen collection, storage, and transport to centralized laboratories. Dried blood spots (DBSs) could circumvent many logistical challenges at the cost of increased misclassification. Recently, plasma separation cards (PSCs) have become available and, though more expensive, have lower total misclassification than DBSs. METHODS: Using a geospatial model created for optimizing VL utilization in Zambia, we estimated the short-term cost of uptake/correct VL result using either DBSs or PSCs to increase VL access on equipment available in-country. Five scenarios were modeled: (1) plasma only (status quo); (2) plasma at high-volume sites, DBS at low-volume sites; (3) plasma at high-volume sites, PSC at low-volume sites; (4) PSC only; (5) DBS only. RESULTS: Scenario 1 resulted in 795 342 correct results due to limited patient access. When allowing for full and partial adoption of dried specimens, access increases by 19%, with scenario 3 producing the greatest number of correct results expected (929 857). The average cost per correct VL result was lowest in the plasma + DBS scenario at $30.90 compared to $31.62 in our plasma + PSC scenario. The cost per correct result of using dried specimens only was dominated in the incremental analysis, due primarily to fewer correct results. CONCLUSIONS: Adopting the partial use of dried specimens will help achieve improved VL access for patients at the lowest cost per correct result.

Continuous quality monitoring in the field: an evaluation of the performance of the Fio Deki Reader™ for rapid HIV testing in South Africa.

BACKGROUND: Rapid diagnostic tests (RDTs) are a cornerstone of HIV diagnosis and rely on good quality processing and interpretation, particularly in the era of test and treat. The Deki Reader (Fio Corporation®, Toronto, Ontario, Canada) is a portable device designed specifically for analysing RDTs and was selected for evaluation in South Africa in the context of HIV RDT analysis. METHODS: This study consisted of a laboratory evaluation and two-part field evaluation of the Deki Reader v100, covering two RDT testing algorithms, and an evaluation of the continuous quality monitoring through the Fionet™ web portal. Based on user feedback from the field evaluation, the device underwent hardware and software redesign, and the Deki Reader v200 was evaluated in the laboratory. Ethics approval for this evaluation was obtained from the University of the Witwatersrand Human Research Ethics Committee: M150160. RESULTS: The intra- and inter-device laboratory precision of the Deki Reader v100 were 98.3 and 99.2% respectively, and 99.3 and 100% for the Deki Reader v200. The laboratory concordances compared to standard-of-care reporting were 99.5 and 98.0% for the two respective models, while sensitivity and specificity were 99.5 and 99.4% for the Deki Reader V100 and 100 and 93.1% for the Deki Reader V200 respectively. Screening and confirmatory concordances in the field were 99.3 and 96.5% under algorithm 1 and 99.7 and 100% under algorithm 2. Sensitivity and specificity for the field evaluation were 99.8 and 97.7%. Overall robustness of the device was acceptable and continuous quality monitoring through Fionet™ was feasible. CONCLUSIONS: The Deki Reader provides an option for improved and reliable quality assessment for rapid diagnosis of HIV using RDTs to enhance the quality of healthcare at the point-of-care. However, the introduction of new RDTs and modification of current algorithms necessitates ongoing and agile RDT reader adjustments, which will require cost modelling to ensure sustainability of devices implemented into national HIV programs.

Assessing the cost and utilization of SMS printers by primary health care facilities: lessons learned from South Africa.

Background: Historically, paper-based laboratory reports were delivered by couriers to health facilities resulting in post-analytical delays. As a result, short message service (SMS) printers were deployed to fill this gap, with the global data service platform (GDSP) being primarily used to facilitate deployment. In addition, these printers generate binary and quantitative information that can be used to assess utilization. Objective: The objective of this study was to determine the costs and utilization of the SMS printer program in South Africa. Methods: A cost analysis for 2020 was undertaken. We determined annual equivalent costs (AEC) for staffing, printers, fixed costs related to the national coordinator, consumables, travel costs, database support/hosting/dashboard development, printer repairs, and results transmission. The main outcome of interest was the cost per SMS printer result delivered. Data were extracted to assess utilization as follows: i) months active (based on internet protocol data); ii) signal; iii) battery strength. Results: There were 4,450,116 results delivered to printers that were situated at 2232 primary health care facilities. An AEC of $687,727 was reported, with a cost per result delivered of $0.1618. The SMS printers contributed 73.52% to the total AEC. Overall, 90% of the printers were GDSP based, of which only 69.5% were determined to be active. The majority of active printers reported a signal strength of ≥60% and a battery strength of ≥6 volts. Conclusion: Although the SMS printer program has the potential to reduce post-analytical delays, pathology services should migrate to an end-to-end electronic interface to improve patient care.

Implementation of an mHealth App to Promote Engagement During HIV Care and Viral Load Suppression in Johannesburg, South Africa (iThemba Life): Pilot Technical Feasibility and Acceptability Study.

BACKGROUND: South Africa has the largest HIV treatment program worldwide. Retention in care and medication adherence remain problematic necessitating innovative solutions for improving HIV care. The increasing availability and use of mobile technology can support positive clinical outcomes for persons living with HIV. iThemba Life is a mobile health app designed with input from South African health professionals and patients, promoting engagement with HIV care through access to medical results. OBJECTIVE: This study aimed to test the feasibility and acceptability of receiving HIV viral load (VL) results through the app and compare the time to HIV VL result return for study participants before and after app use. METHODS: Using convenience sampling, adults having routine VL phlebotomy were recruited from 2 Johannesburg health facilities. After signed consent, the app was downloaded on their Android smartphones, phlebotomy was performed, and the sample barcode was scanned through their phone to link the sample and app. Participants received a notification of the result availability and logged into the app to view results, their explanation and recommended action. RESULTS: Overall, 750 people were screened to enroll 500 participants. Of 750, 113 (15.1%) failed eligibility screening. 21.5% (137/637) had smartphone technical limitations preventing enrollment. Results were released to 92.2% (461/500) of participants' phones. App technical issues and laboratory operational issues limited the number of released results. Approximately 78.1% (360/461) results were viewed in the app. Median time from notification of availability to result viewed being 15.5 hours (0.6; range 0-150 days). Turnaround time from phlebotomy to the result being received was 6 (range 1-167) days for users versus 56 days (range 10-430 days; P<.001) before app use. Overall, 4% (20/500) of participants received unsuppressed results (VL>1000 copies/mL). Turnaround time for unsuppressed results was 7 days for participants versus 37.5 days before app use (P<.001). The difference before and after app use in the suppressed and unsuppressed users for time from sample collection to result delivery was statistically significant. Of 20 participants, 12 (60%) returned for a confirmatory VL during the study period. The time from an unsuppressed VL to a confirmatory VL was 106 days for app users versus 203 days before app use (P<.001). Overall, 52.4% (262/500) of participants completed an exit survey; 23.2% (58/250) reported challenges in viewing their VL results. Moreover, 58% (35/60) reported that they overcame challenges with technical assistance from others, and 97.3% (255/262) wanted to continue using the app for VL results. CONCLUSIONS: Using iThemba Life for VL results was well-received despite limited smartphone access for some participants. App users received results 10 times sooner than before the app and 5 times sooner if their VL >1000 copies/mL. This increased notification speed led to participants wanting to continue using iThemba Life.

Monitoring viral load for the last mile: what will it cost?

INTRODUCTION: Routine viral load testing is the WHO-recommended method for monitoring HIV-infected patients on ART, and many countries are rapidly scaling up testing capacity at centralized laboratories. Providing testing access to the most remote populations and facilities (the "last mile") is especially challenging. Using a geospatial optimization model, we estimated the incremental costs of accessing the most remote 20% of patients in Zambia by expanding the transportation network required to bring blood samples from ART clinics to centralized laboratories and return results to clinics. METHODS: The model first optimized a sample transportation network (STN) that can transport 80% of anticipated sample volumes to centralized viral load testing laboratories on a daily or weekly basis, in line with Zambia's 2020 targets. Data incorporated into the model included the location and infrastructure of all health facilities providing ART, location of laboratories, measured distances and drive times between the two, expected future viral load demand by health facility, and local cost estimates. We then continued to expand the modelled STN in 5% increments until 100% of all samples could be collected. RESULTS AND DISCUSSION: The cost per viral load test when reaching 80% patient volumes using centralized viral load testing was a median of $18.99. With an expanded STN, the incremental cost per test rose to $20.29 for 80% to 85% and $20.52 for 85% to 90%. Above 90% coverage, the incremental cost per test increased substantially to $31.57 for 90% to 95% and $51.95 for 95% to 100%. The high numbers of kilometres driven per sample transported and large number of vehicles needed increase costs dramatically for reaching the clinics that serve the last 5% of patients. CONCLUSIONS: Providing sample transport services to the most remote clinics in low- and middle-income countries is likely to be cost-prohibitive. Other strategies are needed to reduce the cost and increase the feasibility of making viral load monitoring available to the last 10% of patients. The cost of alternative methods, such as optimal point-of-care viral load equipment placement and usage, dried blood/plasma spot specimen utilization, or use of drones in geographically remote facilities, should be evaluated.

Improving Linkage to and Retention in Care in Newly Diagnosed HIV-Positive Patients Using Smartphones in South Africa: Randomized Controlled Trial.

BACKGROUND: South Africa provides free antiretroviral therapy for almost 5 million people living with HIV, but only 71% of the eligible people are on treatment, representing a shortfall in the care cascade, especially among men and youth. Many developing countries have expanded access to smartphones; success in health apps raises the possibility of improving this cascade. OBJECTIVE: SmartLink is a health app for Android smartphones providing HIV-related laboratory results, information, support, and appointment reminders to engage and link patients to care. This study aimed to evaluate the ability of SmartLink to improve linkage to care for HIV-positive smartphone owners. METHODS: This study was a multisite randomized controlled trial in Johannesburg. The intervention arm received the app (along with referral to a treatment site) and the control arm received the standard of care (referral alone). Linkage to care was confirmed by an HIV-related blood test reported on the National Health Laboratory Service database between 2 weeks and 8 months after initiation. RESULTS: A total of 345 participants were recruited into the study; 64.9% (224/345) of the participants were female and 44.1% (152/345) were aged less than 30 years. In addition, 46.7% (161/345) were employed full time, 95.9% (331/345) had at least secondary school education, and 35.9% (124/345) were from Zimbabwe. Linkage to care between 2 weeks and 8 months was 48.6% (88/181) in the intervention arm versus 45.1% (74/164) in the control (P=.52) and increased to 64.1% (116/181) and 61.0% (100/164) (P=.55), respectively, after the initial 8-month period. Moreover, youth aged 18 to 30-years showed a statistically significant 20% increase in linkage to care for the intervention group. CONCLUSIONS: Youth aged less than 30 years have been historically difficult to reach with traditional interventions, and the SmartLink app provides a proof of concept that this population reacts to mobile health interventions that engage patients in HIV care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02756949; https://clinicaltrials.gov/ct2/show/NCT02756949 (Archived by WebCite at http://www.webcitation.org/6z1GTJCNW).

Impact of a borderless sample transport network for scaling up viral load monitoring: results of a geospatial optimization model for Zambia.

INTRODUCTION: The World Health Organization recommends viral load (VL) monitoring at six and twelve months and then annually after initiating antiretroviral treatment for HIV. In many African countries, expansion of VL testing has been slow due to a lack of efficient blood sample transportation networks (STN). To assist Zambia in scaling up testing capacity, we modelled an optimal STN to minimize the cost of a national VL STN. METHODS: The model optimizes a STN in Zambia for the anticipated 1.5 million VL tests that will be needed in 2020, taking into account geography, district political boundaries, and road, laboratory and facility infrastructure. We evaluated all-inclusive STN costs of two alternative scenarios: (1) optimized status quo: each district provides its own weekly or daily sample transport; and (2) optimized borderless STN: ignores district boundaries, provides weekly or daily sample transport, and reaches all Scenario 1 facilities. RESULTS: Under both scenarios, VL testing coverage would increase to from 10% in 2016 to 91% in 2020. The mean transport cost per VL in Scenario 2 was $2.11 per test (SD $0.28), 52% less than the mean cost/test in Scenario 1, $4.37 (SD $0.69), comprising 10% and 19% of the cost of a VL respectively. CONCLUSIONS: An efficient STN that optimizes sample transport on the basis of geography and test volume, rather than political boundaries, can cut the cost of sample transport by more than half, providing a cost savings opportunity for countries that face significant resource constraints.

Improving Linkage to HIV Care Through Mobile Phone Apps: Randomized Controlled Trial.

BACKGROUND: In HIV treatment program, gaps in the "cascade of care" where patients are lost between diagnosis, laboratory evaluation, treatment initiation, and retention in HIV care, is a well-described challenge. Growing access to internet-enabled mobile phones has led to an interest in using the technology to improve patient engagement with health care. OBJECTIVE: The objectives of this trial were: (1) to assess whether a mobile phone-enabled app could provide HIV patients with laboratory test results, (2) to better understand the implementation of such an intervention, and (3) to determine app effectiveness in improving linkage to HIV care after diagnosis. METHODS: We developed and tested an app through a randomized controlled trial carried out in several primary health care facilities in Johannesburg. Newly diagnosed HIV-positive patients were screened, recruited, and randomized into the trial as they were giving a blood sample for initial CD4 staging. Trial eligibility included ownership of a phone compatible with the app and access to the internet. Trial participants were followed for a minimum of eight months to determine linkage to HIV care indicated by an HIV-related laboratory test result. RESULTS: The trial outcome results are being prepared for publication, but here we describe the significant operational and technological lessons provided by the implementation. Android was identified as the most suitable operating system for the app, due to Android functionality and communication characteristics. Android also had the most significant market share of all smartphone operating systems in South Africa. The app was successfully developed with laboratory results sent to personal smartphones. However, given the trial requirements and the app itself, only 10% of screened HIV patients successfully enrolled. We report on issues such as patient eligibility, app testing in a dynamic phone market, software installation and compatibility, safe identification of patients, linkage of laboratory results to patients lacking unique identifiers, and present lessons and potential solutions. CONCLUSIONS: The implementation challenges and lessons of this trial may assist future similar mHealth interventions to avoid some of the pitfalls. Ensuring sufficient expertise and understanding of the programmatic needs by the software developer, as well as in the implementation team, with adequate and rapid piloting within the target groups, could have led to better trial recruitment. However, the majority of screened patients were interested in the study, and the app was installed successfully in patients with suitable smartphones, suggesting that this may be a way to engage patients with their health care data in future. TRIAL REGISTRATION: ClinicalTrials.gov NCT02756949; https://clinicaltrials.gov/ct2/show/NCT02756949 (Archived by WebCite at http://www.webcitation.org/6z1GTJCNW).

A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion.

We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR+ Ki67+ on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67+ HLA-DR+ Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67+ HLA-DR+ T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ+ IL2+ TNFα+ CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67+ HLA-DR+) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment.