Point of Care CD4 Testing in National Household Surveys - Results and Quality Indicators from Eleven Population-Based HIV Impact Assessment (PHIA) Surveys.

Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm3) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps.

A Comprehensive Approach to Assuring Quality of Laboratory Testing in HIV Surveys: Lessons Learned From the Population-Based HIV Impact Assessment Project.

BACKGROUND: Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys. METHODS: Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results. RESULTS: Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160-387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing. CONCLUSIONS: Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries.

Data Architecture to Support Real-Time Data Analytics for the Population-Based HIV Impact Assessments.

BACKGROUND AND SETTING: Electronic data capture facilitates timely use of data. Population-based HIV impact assessments (PHIAs) were led by host governments, with funding from the President's Emergency Plan for AIDS Relief, technical assistance from the Centers for Disease Control, and implementation support from ICAP at Columbia University. We described data architectures, code-based processes, and resulting data volume and quality for 14 national PHIA surveys with concurrent timelines and varied country-level data governance (2015-2020). METHODS: PHIA project data were collected through tablets, point-of-care and laboratory testing instruments, and inventory management systems, using open-source software, vendor solutions, and custom-built software. Data were securely uploaded to the PHIA data warehouse daily or weekly and then used to populate survey-monitoring dashboards and return timely laboratory-based test results on an ongoing basis. Automated data processing allowed timely reporting of survey results. RESULTS: Fourteen data architectures were successfully established, and data from more than 450,000 participants in 30,000 files across 13 countries with completed PHIAs, and blood draws producing approximately 6000 aliquots each week per country, were securely collected, transmitted, and processed by 17 full-time equivalent staff. More than 25,600 viral load results were returned to clinics of participants' choice. Data cleaning was not needed for 98.5% of household and 99.2% of individual questionnaires. CONCLUSION: The PHIA data architecture permitted secure, simultaneous collection and transmission of high-quality interview and biomarker data across multiple countries, quick turnaround time of laboratory-based biomarker results, and rapid dissemination of survey outcomes to guide President's Emergency Plan for AIDS Relief epidemic control.

Successful Use of Near Point-of-Care Early Infant Diagnosis in NAMPHIA to Improve Turnaround Times in a National Household Survey.

BACKGROUND: In the population-based HIV impact assessment surveys, early infant diagnosis (EID) was provided to infants <18 months without a prior diagnosis. For the Namibia population-based HIV impact assessment (NAMPHIA), the GeneXpert platform was assessed for the feasibility of near POC EID testing compared with the standard Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) platform. Quality assurance measures and turnaround time were compared to improve EID results reporting. METHODS: NAMPHIA participants were screened for HIV exposure using Determine HIV-1/2 rapid test; samples reactive on Determine received EID testing on the GeneXpert instrument and Xpert HIV-1 Qual assay using whole blood. Results were confirmed at the Namibia Institute of Pathology using dried blood spots on the Roche CAP/CTM platform per national guidelines. RESULTS: Of the 762 screened infants, 61 (8.0%) were Determine-reactive and considered HIV-exposed. Of the 61 exposed infants, 2 were found to be HIV-infected whereas 59 were negative on both GeneXpert and Roche platforms, achieving 100% concordance. Average turnaround time was 3.4 days for the Xpert HIV-1 Qual assay, and average time from collection to testing was 1.0 days for GeneXpert compared with 10.7 days for Roche. No samples failed using GeneXpert whereas 1 sample failed using Roche and was repeated. CONCLUSION: Quality POC EID testing is feasible in a national survey through extensive training and external quality assurance measures. The use of decentralized POC EID for national testing would provide rapid diagnosis and improve TATs which may prevent loss to follow-up, ensure linkage to care, and improve clinical outcomes for infants.

Returning HIV-1 viral load results to participant-selected health facilities in national Population-based HIV Impact Assessment (PHIA) household surveys in three sub-Saharan African Countries, 2015 to 2016.

INTRODUCTION: Logistical complexities of returning laboratory test results to participants have precluded most population-based HIV surveys conducted in sub-Saharan Africa from doing so. For HIV positive participants, this presents a missed opportunity for engagement into clinical care and improvement in health outcomes. The Population-based HIV Impact Assessment (PHIA) surveys, which measure HIV incidence and the prevalence of viral load (VL) suppression in selected African countries, are returning VL results to health facilities specified by each HIV positive participant within eight weeks of collection. We describe the performance of the specimen and data management systems used to return VL results to PHIA participants in Zimbabwe, Malawi and Zambia. METHODS: Consenting participants underwent home-based counseling and HIV rapid testing as per national testing guidelines; all confirmed HIV positive participants had VL measured at a central laboratory on either the Roche CAP/CTM or Abbott m2000 platform. On a bi-weekly basis, a dedicated data management team produced logs linking the VL test result with the participants' contact information and preferred health facility; project staff sent test results confidentially via project drivers, national courier systems, or electronically through an adapted short message service (SMS). Participants who provided cell phone numbers received SMS or phone call alerts regarding availability of VL results. RESULTS AND DISCUSSION: From 29,634 households across the three countries, 78,090 total participants 0 to 64 years in Zimbabwe and Malawi and 0 to 59 years in Zambia underwent blood draw and HIV testing. Of the 8391 total HIV positive participants identified, 8313 (99%) had VL tests performed and 8245 (99%) of these were returned to the selected health facilities. Of the 5979 VL results returned in Zimbabwe and Zambia, 85% were returned within the eight-week goal with a median turnaround time of 48 days (IQR: 33 to 61). In Malawi, where exact return dates were unavailable all 2266 returnable results reached the health facilities by 11 weeks. CONCLUSIONS: The first three PHIA surveys returned the vast majority of VL results to each HIV positive participant's preferred health facility within the eight-week target. Even in the absence of national VL monitoring systems, a system to return VL results from a population-based survey is feasible, but it requires developing laboratory and data management systems and dedicated staff. These are likely important requirements to strengthen return of results systems in routine clinical care.