Susan H Eshleman1, Estelle Piwowar-Manning1, Ethan A Wilson2, Denni Lennon1, Jessica M Fogel1, Yaw Agyei1, Philip A Sullivan1, Lei Weng2, Ayana Moore3, Oliver Laeyendecker4, Barry Kosloff5,6, Justin Bwalya5, Gerald Maarman7, Anneen van Deventer8, Sian Floyd9, Peter Bock7, Helen Ayles5,6, Sarah Fidler10, Richard Hayes9, Deborah Donnell2. 1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 3. FHI360, Durham, NC, USA. 4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Zambart, University of Zambia School of Medicine, Lusaka, Zambia. 6. Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK. 7. Desmond Tutu TB Center, Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, Western Cape, South Africa. 8. Stellenbosch University, Stellenbosch, Western Cape, South Africa. 9. Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. 10. Imperial College London, London, UK.
Abstract
INTRODUCTION: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates.
INTRODUCTION: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates.
Authors: Jessica M Fogel; Ethan A Wilson; Estelle Piwowar-Manning; Autumn Breaud; William Clarke; Christos Petropoulos; Ayana Moore; Christophe Fraser; Barry Kosloff; Kwame Shanaube; Gert van Zyl; Michelle Scheepers; Sian Floyd; Peter Bock; Helen Ayles; Sarah Fidler; Richard Hayes; Deborah Donnell; Susan H Eshleman Journal: J Int AIDS Soc Date: 2022-07 Impact factor: 6.707
Authors: Ethan Klock; Ethan Wilson; Reinaldo E Fernandez; Estelle Piwowar-Manning; Ayana Moore; Barry Kosloff; Justin Bwalya; Nomtha Bell-Mandla; Anelet James; Helen Ayles; Peter Bock; Deborah Donnell; Sarah Fidler; Richard Hayes; Susan H Eshleman; Oliver Laeyendecker Journal: J Int AIDS Soc Date: 2021-12 Impact factor: 6.707
Authors: Wendy Grant-McAuley; Ethan Klock; Oliver Laeyendecker; Estelle Piwowar-Manning; Ethan Wilson; William Clarke; Autumn Breaud; Ayana Moore; Helen Ayles; Barry Kosloff; Kwame Shanaube; Peter Bock; Nomtha Mandla; Anneen van Deventer; Sarah Fidler; Deborah Donnell; Richard Hayes; Susan H Eshleman Journal: PLoS One Date: 2021-12-17 Impact factor: 3.752
Authors: Amy S Sturt; Emily L Webb; Comfort R Phiri; Maina Mudenda; Joyce Mapani; Barry Kosloff; Maina Cheeba; Kwame Shanaube; Justin Bwalya; Eyrun F Kjetland; Suzanna C Francis; Paul L A M Corstjens; Govert J van Dam; Lisette van Lieshout; Isaiah Hansingo; Helen Ayles; Richard J Hayes; Amaya L Bustinduy Journal: Open Forum Infect Dis Date: 2021-06-30 Impact factor: 3.835