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Validation of the Limiting Antigen Avidity Assay to Estimate Level and Trends in HIV Incidence in an A/D epidemic in Rakai, Uganda

Objective: The Limiting-Antigen Avidity Assay (LAg-Avidity) with viral load >1000 copies/ml is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Methods: Sera from persons seen in two surveys (... Full description

Journal Title: AIDS research and human retroviruses 2018, Vol.35 (ja), p.364-367
Main Author: Laeyendecker, Oliver
Other Authors: Gray, Ronald , Grabowski, Mary , Reynolds, Steven , Ndyanabo, Anthony , Ssekasanvu, Joseph , Fernandez, Reinaldo , Wawer, Maria , Serwadda, David , Quinn, Thomas C
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
Quelle: Alma/SFX Local Collection
Publisher: United States: Mary Ann Liebert, Inc
ID: ISSN: 0889-2229
Link: https://www.ncbi.nlm.nih.gov/pubmed/30560723
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6461304
title: Validation of the Limiting Antigen Avidity Assay to Estimate Level and Trends in HIV Incidence in an A/D epidemic in Rakai, Uganda
format: Article
creator:
  • Laeyendecker, Oliver
  • Gray, Ronald
  • Grabowski, Mary
  • Reynolds, Steven
  • Ndyanabo, Anthony
  • Ssekasanvu, Joseph
  • Fernandez, Reinaldo
  • Wawer, Maria
  • Serwadda, David
  • Quinn, Thomas C
subjects:
  • Adjustment
  • Adolescent
  • Adult
  • AIDS/HIV
  • Antibody Affinity
  • Antigens
  • Assaying
  • Avidity
  • Cohort Studies
  • Confidence intervals
  • Constraining
  • cross-sectional incidence estimation
  • Disease control
  • Epidemics
  • Epidemiology
  • HIV
  • HIV Antibodies - immunology
  • HIV Antigens - blood
  • HIV Infections - diagnosis
  • HIV Infections - epidemiology
  • Human immunodeficiency virus
  • Humans
  • Incidence
  • Middle Aged
  • Serologic Tests - methods
  • Serologic Tests - standards
  • Trends
  • Uganda
  • Uganda - epidemiology
  • validation
  • Viral Load - methods
  • Young Adult
ispartof: AIDS research and human retroviruses, 2018, Vol.35 (ja), p.364-367
description: Objective: The Limiting-Antigen Avidity Assay (LAg-Avidity) with viral load >1000 copies/ml is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Methods: Sera from persons seen in two surveys (2008-09 and 2012-13) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0% was compared to subtype-specific MDRI and FRR, adjusted to subtype distributions. Results: The observed incidence was 1.05/100 person-years (py) (95%CI 0.90, 1.23) in 2008-09, and 0.66/100 py (95%CI 0.52, 0.83) in 2012-2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95%CI 0.97, 2.30) in 2008-09, and 2.55/100 py (95% CI 1.51, 3.59) in 2012-13 (a significant increase, P
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0889-2229
fulltext: fulltext
issn:
  • 0889-2229
  • 1931-8405
url: Link


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titleValidation of the Limiting Antigen Avidity Assay to Estimate Level and Trends in HIV Incidence in an A/D epidemic in Rakai, Uganda
sourceAlma/SFX Local Collection
creatorLaeyendecker, Oliver ; Gray, Ronald ; Grabowski, Mary ; Reynolds, Steven ; Ndyanabo, Anthony ; Ssekasanvu, Joseph ; Fernandez, Reinaldo ; Wawer, Maria ; Serwadda, David ; Quinn, Thomas C
creatorcontribLaeyendecker, Oliver ; Gray, Ronald ; Grabowski, Mary ; Reynolds, Steven ; Ndyanabo, Anthony ; Ssekasanvu, Joseph ; Fernandez, Reinaldo ; Wawer, Maria ; Serwadda, David ; Quinn, Thomas C
descriptionObjective: The Limiting-Antigen Avidity Assay (LAg-Avidity) with viral load >1000 copies/ml is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Methods: Sera from persons seen in two surveys (2008-09 and 2012-13) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0% was compared to subtype-specific MDRI and FRR, adjusted to subtype distributions. Results: The observed incidence was 1.05/100 person-years (py) (95%CI 0.90, 1.23) in 2008-09, and 0.66/100 py (95%CI 0.52, 0.83) in 2012-2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95%CI 0.97, 2.30) in 2008-09, and 2.55/100 py (95% CI 1.51, 3.59) in 2012-13 (a significant increase, P<0.05.) However, using a subtype specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95%CI 0.44, 1.33) in 2008-09 and 0.67% (95%CI 0.00, 1.68) in 2012-13, approximating to the observed incidence trends. Conclusions: In this subtype A/D epidemic, the per protocol LAg-Avidity +VL assay overestimated HIV incidence and failed to detect declines in incidence. Adjustment for FRR, MDRI and subtype distribution, provided incidence estimates similar to empirically observed incidence level and trends. Thus, use of the LAg-Avidity assay in an A/D epidemic, requires adjustment for subtype.
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subjectAdjustment ; Adolescent ; Adult ; AIDS/HIV ; Antibody Affinity ; Antigens ; Assaying ; Avidity ; Cohort Studies ; Confidence intervals ; Constraining ; cross-sectional incidence estimation ; Disease control ; Epidemics ; Epidemiology ; HIV ; HIV Antibodies - immunology ; HIV Antigens - blood ; HIV Infections - diagnosis ; HIV Infections - epidemiology ; Human immunodeficiency virus ; Humans ; Incidence ; Middle Aged ; Serologic Tests - methods ; Serologic Tests - standards ; Trends ; Uganda ; Uganda - epidemiology ; validation ; Viral Load - methods ; Young Adult
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6Fernandez, Reinaldo
7Wawer, Maria
8Serwadda, David
9Quinn, Thomas C
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descriptionObjective: The Limiting-Antigen Avidity Assay (LAg-Avidity) with viral load >1000 copies/ml is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Methods: Sera from persons seen in two surveys (2008-09 and 2012-13) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0% was compared to subtype-specific MDRI and FRR, adjusted to subtype distributions. Results: The observed incidence was 1.05/100 person-years (py) (95%CI 0.90, 1.23) in 2008-09, and 0.66/100 py (95%CI 0.52, 0.83) in 2012-2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95%CI 0.97, 2.30) in 2008-09, and 2.55/100 py (95% CI 1.51, 3.59) in 2012-13 (a significant increase, P<0.05.) However, using a subtype specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95%CI 0.44, 1.33) in 2008-09 and 0.67% (95%CI 0.00, 1.68) in 2012-13, approximating to the observed incidence trends. Conclusions: In this subtype A/D epidemic, the per protocol LAg-Avidity +VL assay overestimated HIV incidence and failed to detect declines in incidence. Adjustment for FRR, MDRI and subtype distribution, provided incidence estimates similar to empirically observed incidence level and trends. Thus, use of the LAg-Avidity assay in an A/D epidemic, requires adjustment for subtype.
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18HIV Infections - diagnosis
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20Human immunodeficiency virus
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22Incidence
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24Serologic Tests - methods
25Serologic Tests - standards
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27Uganda
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titleValidation of the Limiting Antigen Avidity Assay to Estimate Level and Trends in HIV Incidence in an A/D epidemic in Rakai, Uganda
authorLaeyendecker, Oliver ; Gray, Ronald ; Grabowski, Mary ; Reynolds, Steven ; Ndyanabo, Anthony ; Ssekasanvu, Joseph ; Fernandez, Reinaldo ; Wawer, Maria ; Serwadda, David ; Quinn, Thomas C
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abstractObjective: The Limiting-Antigen Avidity Assay (LAg-Avidity) with viral load >1000 copies/ml is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Methods: Sera from persons seen in two surveys (2008-09 and 2012-13) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0% was compared to subtype-specific MDRI and FRR, adjusted to subtype distributions. Results: The observed incidence was 1.05/100 person-years (py) (95%CI 0.90, 1.23) in 2008-09, and 0.66/100 py (95%CI 0.52, 0.83) in 2012-2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95%CI 0.97, 2.30) in 2008-09, and 2.55/100 py (95% CI 1.51, 3.59) in 2012-13 (a significant increase, P<0.05.) However, using a subtype specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95%CI 0.44, 1.33) in 2008-09 and 0.67% (95%CI 0.00, 1.68) in 2012-13, approximating to the observed incidence trends. Conclusions: In this subtype A/D epidemic, the per protocol LAg-Avidity +VL assay overestimated HIV incidence and failed to detect declines in incidence. Adjustment for FRR, MDRI and subtype distribution, provided incidence estimates similar to empirically observed incidence level and trends. Thus, use of the LAg-Avidity assay in an A/D epidemic, requires adjustment for subtype.
copUnited States
pubMary Ann Liebert, Inc
pmid30560723
doi10.1089/AID.2018.0207
oafree_for_read