Integrated Testing on the GeneXpert Optimizing utilization of existing GeneXpert devices in Zimbabwe to expand access to testing for EID, TB/MDR-TB and HIV Viral Load

Background Information on existing GeneXpert® platforms in Zimbabwe Currently Zimbabwe has 130 GeneXpert® devices placed across districts and selected health facilities Until September 2016 all GeneXpert® devices were used for TB testing only In the past, these platforms have hardly achieved 27% of their established capacities The one 4-module GeneXpert® machine has the estimated capacity to run a maximum of 2,880 tests per year The TB and HIV programs agreed to do a pilot in order to make informed decision about TB & HIV integration The 2,880 is based on 16 TB tests per day (240 working days/year and 6 hours operation per day);

WIN TB HIV program program The existing TB GeneXpert® excess testing capacity can be used for EID and VL testing for the mutual benefit of all programs Pros Increased TB case finding through targeted testing of HIV high risk presumptive population Share operational costs with the HIV program Pros Improved outcomes for PLHIV detecting TB early Improved care outcomes for patients on ART Facilitate Early diagnosis of HEI (HIV Exposed Infants) and enrolment to care of HII (HIV Infected Infants) Devices already in country and placed TB program HIV program WIN Pros for both programs and MoH: No device dumping in laboratories with already limited bench space Efficiencies in operational costs  Increased negotiating power with Cepheid for cartridge prices & S&M Progressive collaboration across programs

The aim of the integration pilot is to determine the feasibility of providing high quality and timely EID, TB, and VL testing on the existing Xpert® devices Goal To demonstrate how spare capacity across existing Xpert® devices could be utilized by both HIV and TB programs to ensure improved access to TB testing, EID and HIV VL testing at health facilities and optimize workflow and device usage. Expected Outcomes Patient Impact Assessment Feasibility Assessment Acceptability Assessment Objectives Determine the feasibility of providing high quality and timely EID, TB and VL testing on existing Xpert® devices that are currently only being used for TB diagnosis at 10 health care facilities in Zimbabwe over 6 months. Determine the optimal flow of patients, samples and results for integrated testing at health facilities included in the pilot.. Phase 1 Phase 2 Determine the acceptability of integrated testing on the 4M Xpert® by clinicians and lab personnel in the 10 public health facilities. Assess the patient impact of integrated testing on existing Xpert® platforms at the 10 health facilities over a period of 6months.

Site Selection Process 1 Site selection criteria: Used existing available information from both TB and HIV programs Existing sites (TB GX, EID, ART) Patient volume Access to regional labs TB/HIV prevalence ART coverage Spare capacity Sites with: High/moderate volume of TB suspects (>200 in 2015) High volume of ART patients (>1500 patients on ART) Sites with: Existing access to conventional VL and EID testing at regional molecular labs Long TAT (>4 weeks) for EID and VL 2015 Xpert® utilization rate < 35% 2 Preliminary Selection: Assessment of sites to determine spare capacity Xpert ®Testing Capacity HIV Testing Need at the Facility Annual TB testing volume # Adults on ART (proxy for adult VL testing need) Annual TB testing need # Children on ART (proxy for children VL testing need) Spare annual testing capacity which could be used for HIV testing # Exposed infants (proxy for EID testing need) Operating hours per day or days per month and device downtime per month Annual EID testing volume and VL testing volume 3 Site visit : to confirm prelim assessment and readiness of facility to support implementation pilot and take ownership beyond pilot

Ten sites met these criteria and selected for the pilot Three provincial hospitals, four district hospitals and three polyclinics have been purposively selected to represent the types of public health institutions in Zimbabwe

EID TB VL Patient Population Onsite EID testing for all infants between 6 weeks and 18months’ old requiring a test. TB From September to December 2016, TB testing for HIV co-infected patients and DR-TB suspects. Starting January 2017, due to change in national TB algorithm, sputum samples collected from all TB suspects for initial TB diagnosis VL Onsite viral load testing initially targeted for pregnant and lactating mothers, children, treatment failure suspects and patients highly susceptible to LTFU (due to long traveling distances, financial constraints and other factors as determined by clinicians)

Key implementation considered at the beginning of the pilot The existing GeneXpert® devices in the country were acquired through the National TB program and are thus prioritized for TB testing Following analysis, EID volumes are very manageable for each site and a decision was made to test all HIV exposed infants using the onsite GeneXpert® At the early stage of the pilot, onsite VL testing was available to all patients who were in need of testing however, due to changed of TB testing algorithm, VL testing were reserved for targeted patients beginning January 2017 The flow of patients, samples and results is left to the discretion of the facility. Nurses are responsible for deciding which patients were eligible for testing on the GeneXpert®; on observation, all pilot sites prioritized EID testing over TB and VL. Targeted patients presented in previous slide ( slide 7)

Preliminary pilot data provides evidence supporting feasibility of integrated testing on the GX 1 TB testing patterns maintained: TB samples were prioritized for testing over viral load specimens. EID specimens prioritized over TB specimens due to the need to quickly initiate babies on ART and due the low volume of EID specimens, this prioritization schedule did not cause any significant disruptions to TB testing patterns 2 Device maximum utilization not fully reached: Average utilization rate for the pilot sites was 12.7% prior to the pilot and this has increased to 31.1%. With the change in the TB testing algorithm beginning this year, NTP estimated that 65% of the capacity will be utilized by TB testing only. With each device maximum throughput of 90% , approximately 25% potential capacity can still be leveraged for HIV related tests while maintaining TB testing patterns. 3 Work flow models observed at the facilities Nurses from the clinic/ward collect samples and deliver the samples to the lab Patients present themselves to the lab for sample collection Lab staff go to the clinic/ward to collect samples Workflow Models observed during supervision –, 1nurses collect samples and deliver the samples to the lab. Lab staff test the samples and place the results at a dispatch counter, where nurses could collect the results during their sample delivery ran. In one facility, the nurses affixing “Urgent” stickers to samples they regarded as priority. The lab prioritized these samples with sticker and call the nurses when the results were available. This model was observed to be very efficient in terms of reducing in-lab TAT. Some facilities employed a model where 2patients presented themselves to the lab for sample collection. Results would then be delivered to the referring clinic by the lab staff or 3lab staff go to the clinic/ward to collect samples. Further investigation will be needed to know the impact on result return to patient

Integration Preliminary findings Turnaround time within the lab for all 3 sample types Sample Type Target TAT (hrs) Average of TAT (hrs) Min of TAT Max of TAT EID <24 10.7 1.6 52.0 TB <168 16.0 2.2 147.0 VL 36.5 124.7 All tests 25.6 Sept –December 2016 Test volume increased, improved access In total 2,975 samples (EID +VL) were done on top of the routine TB testing in the lab Not all samples are onsite samples, 51% of samples were referred from other facilities Staffing and equipment breakdowns seriously affected testing volumes Action Plan: Pro-active re-training and mentorship of Lab staff on preventive maintenance and ensure S&M plan for timely servicing Reduced Turnaround time (TAT): Conventional lab average TAT is around 14 days but with integration to a near-POC , the in lab TAT was reduced significantly. 68.2% of EID tests, 51.7% of TB tests and 28.1% of viral load tests run within 24hrs and all samples within 7 days. Baseline TAT for TB testing is within 48 hours so with integration the labs maintained the same level of service as before Action Plan: Set TAT targets for actionable results; TAT from sample collection to result received by the clinician and patient will be tracked in the next phase of the pilot.

Sample Size (Sep-Dec’ 16) Integration Preliminary findings Error Rate by Test Type:   Test type Number of Errors Sample Size (Sep-Dec’ 16) Error Rate EID 2 66 3.0% TB 27 1297 2.1% VL 188 1259 14.9% All tests 217 2622 8.3% Increase in utilization from 12.7% in 2015 to 31.1% during the pilot When fully functional the devices are still underutilized; with average spare capacity of 59% in Q4 2016 Beginning 2017, national TB testing algorithm changed to recommend Xpert testing for all TB suspects for initial diagnosis; this will increase utilization to 65% for TB tests only, leaving 25% remaining spare capacity for EID and VL tests Opportunity for placement of 16 module GX at high volume places Action Plan: In phase 2, testing for VL will focus on targeted patients and those for 2nd VL follow up. TB error rate in 2015 was 7.4% on average at 8 out of 10 pilot sites. 23% of the errors were attributed to insufficient sample volume, others are due to sudden stoppage of test run due to power fluctuations Action Plan: Plan to conduct refresher training and mentorship prior to the start of the next phase. Three pilot sites to run DBS EID in phase 2.

Several key challenges still remain to be addressed for effective integration 1 Investment will need to be put in place to reduce downtown e.g. air conditioners to control temperature, extra fridges to stores samples, solar panels to provide power during times of power cuts. Condition of infrastructure 2 Some of the current machines are older than 5 years, improved vigilance and better S&M services will reduce downtime due to breakdowns Service and maintenance 3 Routine Staff Rotation Redeployment of lab staff trained in GeneXpert EID and VL testing to another facility results in downtime until new personnel can be trained hence the need to train larger pools of testing staff. 4 Waste Management All the pilot facilities do not have incinerators which go up to the 1000°C required to safely dispose of used cartridges. Waste has to be moved to the health facilities with the capacity to incinerate. There is need for a more sustainable solution Refer o notes sent separately to emphasize each point raised

Key Recommendations for successful integration moving forward Policy There is a need to revisit the use of GX devices in the country at a policy level if the HIV/AIDS Program is also to effectively utilize the same machines originally procured for TB testing only. Effective policy will also enable the AIDS and TB programs to realize synergies through cost savings from shared costs like setup, S&M, supportive supervision, supply chain management and HR. Infrastructure Investment on infrastructural upgrade would need to be considered in the event of national scale up. Service and Maintenance New and innovative S&M services will be more important as utilization goes up as the labs would need multiple modules up and running at the same time all the time. Integration provides an opportunity to leverage volumes and funding across programs for better service provision. Refer to notes sent separately

Next steps: Phase 2 of the pilot will run for 3 months beginning August – October 2017 Refresher training and mentorship of trained staff and retraining of new lab staff redeployed in the sites will be conducted prior to phase 2 pilot Data collection will be done and an analysis will be prepared to compare pre and post pilot indicators for TB, EID and VL Presentation of overall findings and recommendations to Program TWGs for endorsement TWGs here include TB, HIV