Development of an approach to monitor the manufacturing consistency of HIV rapid diagnostic tests: Panel qualification and potential impact on country programs

Although regulatory bodies have standards that manufacturers of rapid diagnostic tests (RDTs) must meet for market approval, RDTs have no specific sampling and testing standards to monitor ongoing lot production, unlike pharmaceuticals and certain devices. With the importance of accurate diagnosis for improved health outcomes, independent quality assurance testing is key to ensuring the availability of high-quality RDTs, particularly in low-resource settings. This work develops an approach for HIV RDT lot testing, involving qualification of specimens to enable testing across various RDTs (namely Determine HIV-1/2, OraQuick HIV-1/2, Bioline HIV-1/2 3.0, UniGold HIV, and HIV Ag/Ab Combo). A sampling plan and acceptance criteria were developed per lot (approximating sensitivity and specificity) based on ISO 2859–1: 1999, using the test line response to a qualified panel (disease-positive and negative specimens) as the attribute. Based on general performance of HIV RDTs, an average % defective tests allowed per lot (acceptance quality limit) of 0.65% within ISO 2859–1: 1999 was selected, where RDTs are tested with 80 positives (accept 1 / reject 2 defective results) and 80 negatives (accept 1 / reject 2 defective results) per lot. Panel qualification was conducted with 83 positive and 84 negative serum specimens to select specimens that consistently provided expected results when tested in quadruplicate with three lots per product. While all products yielded consistent results with at least 80 negative specimens, only 4 products did the same for positive specimens. With this approach, each of these 4 RDT products can be tested with the qualified 80-positive specimen panel, requiring the other product to be tested with 20 specimens in quadruplicate. Additionally, this approach was adapted to evaluate HIV antibody/antigen combination tests with Ag panel qualification using p24 samples. While panels were qualified to monitor ongoing lot consistency of HIV RDTs, this approach could be mimicked with other types of diagnostics for monitoring manufacturing consistency, field investigation, small-scale stability checks, and proficiency testing.

[1]  P. Kerndt,et al.  Low and Decreasing Prevalence and Rate of False Positive HIV Diagnosis — Chókwè District, Mozambique, 2014–2017 , 2018, MMWR. Morbidity and mortality weekly report.

[2]  Marie Lina Excellent,et al.  External quality assessment for HIV rapid tests: challenges and opportunities in Haiti , 2018, BMJ Global Health.

[3]  Peter Hughes,et al.  Evaluation of HIV-1 rapid tests and identification of alternative testing algorithms for use in Uganda , 2018, BMC Infectious Diseases.

[4]  J. Bello-López,et al.  External quality control program in screening for infectious diseases at blood banks in Mexico. , 2018, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[5]  P. Drain,et al.  Evaluating quality management systems for HIV rapid testing services in primary healthcare clinics in rural KwaZulu-Natal, South Africa , 2017, PloS one.

[6]  N. Ford,et al.  To err is human, to correct is public health: a systematic review examining poor quality testing and misdiagnosis of HIV status , 2017, Journal of the International AIDS Society.

[7]  A. Puren,et al.  Misdiagnosis of HIV infection during a South African community-based survey: implications for rapid HIV testing , 2017, Journal of the International AIDS Society.

[8]  K. Wilson,et al.  HIV point of care diagnosis: preventing misdiagnosis experience from a pilot of rapid test algorithm implementation in selected communes in Vietnam , 2017, Journal of the International AIDS Society.

[9]  A. Ng'ang'a,et al.  HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites , 2017, Journal of the International AIDS Society.

[10]  A. Ng'ang'a,et al.  Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives , 2017, Journal of the International AIDS Society.

[11]  M. Smallwood,et al.  Improving the Quality of Diagnostic Studies Evaluating Point of Care Tests for Acute HIV Infections: Problems and Recommendations , 2017, Diagnostics.

[12]  Krishna K. Saha,et al.  A Comparison of Some Approximate Confidence Intervals for a Single Proportion for Clustered Binary Outcome Data , 2016, The international journal of biostatistics.

[13]  S. Makombe,et al.  Initial Accuracy of HIV Rapid Test Kits Stored in Suboptimal Conditions and Validity of Delayed Reading of Oral Fluid Tests , 2016, PLoS ONE.

[14]  M. Monze,et al.  Accuracy in HIV Rapid Testing among Laboratory and Non-laboratory Personnel in Zambia: Observations from the National HIV Proficiency Testing System , 2014, PloS one.

[15]  N. Pearce,et al.  Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible? , 2015, PloS one.

[16]  A. Sands Ensuring the quality of HIV testing services , 2015 .

[17]  N. Pearce,et al.  Dilution testing using rapid diagnostic tests in a HIV diagnostic algorithm: a novel alternative for confirmation testing in resource limited settings , 2015, Virology Journal.

[18]  N. Pearce,et al.  Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses , 2015, BMC Infectious Diseases.

[19]  K. Wada,et al.  Ensuring accurate testing for human immunodeficiency virus in Myanmar , 2014, Bulletin of the World Health Organization.

[20]  K. Lokuge,et al.  Variation in Specificity of HIV Rapid Diagnostic Tests over Place and Time: An Analysis of Discordancy Data Using a Bayesian Approach , 2013, PloS one.

[21]  D. Klarkowski,et al.  False Positive HIV Diagnoses in Resource Limited Settings: Operational Lessons Learned for HIV Programmes , 2013, PloS one.

[22]  Ram Yogev,et al.  Rapid HIV testing for developing countries: the challenge of false-negative tests , 2012, Defense + Commercial Sensing.

[23]  D. Charlton,et al.  The effect of simulated field storage conditions on the accuracy of rapid user-friendly blood pathogen detection kits. , 2012, Military medicine.

[24]  Arun Ross,et al.  Sensing Technologies for Global Health, Military Medicine, Disaster Response, and Environmental Monitoring; and Biometric Technology for Human Identification VIII , 2012 .

[25]  R. Gray,et al.  Field evaluation of five rapid diagnostic tests for screening of HIV-1 infections in rural Rakai, Uganda , 2011, International journal of STD & AIDS.

[26]  D. McPhee,et al.  Photographed Rapid HIV Test Results Pilot Novel Quality Assessment and Training Schemes , 2011, PloS one.

[27]  E. Bile,et al.  Ensuring the quality of HIV rapid testing in resource-poor countries using a systematic approach to training. , 2010, American journal of clinical pathology.

[28]  J. Nkengasong,et al.  Scaling up HIV rapid testing in developing countries: comprehensive approach for implementing quality assurance. , 2010, American journal of clinical pathology.

[29]  Teri Dowling,et al.  False Positive Rate of Rapid Oral Fluid HIV Tests Increases as Kits Near Expiration Date , 2009, PloS one.

[30]  D. MacKellar,et al.  Rapid Human Immunodeficiency Virus Test Quality Assurance Practices and Outcomes among Testing Sites Affiliated with 17 Public Health Departments , 2009, Journal of Clinical Microbiology.

[31]  D. McPhee,et al.  Assessing Proficiency of Interpretation of Rapid Human Immunodeficiency Virus Assays in Nonlaboratory Settings: Ensuring Quality of Testing , 2008, Journal of Clinical Microbiology.

[32]  S. Chinn,et al.  Intraclass correlation coefficient and outcome prevalence are associated in clustered binary data. , 2005, Journal of clinical epidemiology.

[33]  R. Newcombe Two-sided confidence intervals for the single proportion: comparison of seven methods. , 1998, Statistics in medicine.

[34]  C. Dolea,et al.  World Health Organization , 1949, International Organization.