Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART)

• Published in: PloS one 2021-12, Vol.16 (12), p.e0258644-e0258644
• Main Authors: Grant-McAuley, Wendy, Klock, Ethan, Laeyendecker, Oliver, Piwowar-Manning, Estelle, Wilson, Ethan, Clarke, William, Breaud, Autumn, Moore, Ayana, Ayles, Helen, Kosloff, Barry, Shanaube, Kwame, Bock, Peter, Mandla, Nomtha, van Deventer, Anneen, Fidler, Sarah, Donnell, Deborah, Hayes, Richard, Eshleman, Susan H
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Algorithms; Analysis; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Antiviral agents; Assaying; Assessments; Avidity; Biology and Life Sciences; Biomarkers; Complications and side effects; Cross-Sectional Studies; Diagnosis; Disease prevention; Female; HIV; HIV infection; HIV Infections - diagnosis; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - virology; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immunoenzyme Techniques; Incidence; Infections; Infectious diseases; Male; Medicine and Health Sciences; Middle Aged; Patient outcomes; Performance evaluation; Physical Sciences; Research and Analysis Methods; Sensitivity analysis; Sensitivity and Specificity; Seroconversion; South Africa - epidemiology; Time Factors; Tutu, Desmond; Viral Load - drug effects; Zambia - epidemiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0258644

Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments. Samples were obtained from 220 seroconverters (infected 1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads ≤400 copies/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay. The MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections >2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression. The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected