Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART).
Adult
Anti-HIV Agents
/ therapeutic use
Antiretroviral Therapy, Highly Active
Cross-Sectional Studies
Female
HIV Infections
/ diagnosis
HIV-1
/ immunology
Humans
Immunoenzyme Techniques
Incidence
Male
Middle Aged
Sensitivity and Specificity
Seroconversion
South Africa
/ epidemiology
Time Factors
Viral Load
/ drug effects
Zambia
/ epidemiology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
04
2021
accepted:
01
10
2021
entrez:
17
12
2021
pubmed:
18
12
2021
medline:
7
1
2022
Statut:
epublish
Résumé
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) and 4,396 non-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 <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments.
Sections du résumé
BACKGROUND
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.
METHODS
Samples were obtained from 220 seroconverters (infected <1 year) and 4,396 non-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.
RESULTS
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.
CONCLUSIONS
The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments.
Identifiants
pubmed: 34919554
doi: 10.1371/journal.pone.0258644
pii: PONE-D-21-12144
pmc: PMC8682874
doi:
Substances chimiques
Anti-HIV Agents
0
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0258644Subventions
Organisme : NIAID NIH HHS
ID : R01 AI095068
Pays : United States
Organisme : PEPFAR
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068619
Pays : United States
Organisme : Medical Research Council
ID : MR/R010161/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : UM1 AI068617
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069521
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068613
Pays : United States
Déclaration de conflit d'intérêts
I have read the journal’s policy and the authors of this manuscript have the following competing interests: None of the authors has a conflict of interest or potential conflict of interest, with the following exceptions: Susan Eshleman has collaborated on research studies with investigators from Abbott Diagnostics; Abbott Diagnostics provided reagents for previous research studies.
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