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

Oliver B. Laeyendecker, Ronald H Gray, Mary Grabowski, Steven James Reynolds, Anthony Ndyanabo, Joseph Ssekasanvu, Reinaldo E. Fernandez, Maria J Wawer, David Serwadda, Thomas C Quinn

Research output: Contribution to journalArticle

Abstract

The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 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. Sera from persons seen in two surveys (2008-2009 and 2012-2013) 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 with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95% confidence interval (CI) 0.90-1.23] in 2008-2009 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 2008-2009 and 2.55/100 py (95% CI 1.51-3.59) in 2012-2013 (a significant increase, p < .05.) However, using a subtype-specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95% CI 0.44-1.33) in 2008-2009 and 0.67% (95% CI 0.00-1.68) in 2012-2013, approximating to the observed incidence trends. 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.

Original languageEnglish (US)
Pages (from-to)364-367
Number of pages4
JournalAIDS research and human retroviruses
Volume35
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Uganda
HIV
Antigens
Incidence
Confidence Intervals
Infection
Viral Load
Eastern Africa
HIV-1

Keywords

  • cross-sectional incidence estimation
  • incidence
  • Uganda
  • validation

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

@article{9b522f685fd94782ad0aeced4dbc1f26,
title = "Validation of the Limiting Antigen Avidity Assay to Estimate Level and Trends in HIV Incidence in an A/D Epidemic in Rakai, Uganda",
abstract = "The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 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. Sera from persons seen in two surveys (2008-2009 and 2012-2013) 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 with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95{\%} confidence interval (CI) 0.90-1.23] in 2008-2009 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 2008-2009 and 2.55/100 py (95{\%} CI 1.51-3.59) in 2012-2013 (a significant increase, p < .05.) However, using a subtype-specific MDRI and FRR, the subtype adjusted incidence was 0.88{\%} (95{\%} CI 0.44-1.33) in 2008-2009 and 0.67{\%} (95{\%} CI 0.00-1.68) in 2012-2013, approximating to the observed incidence trends. 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.",
keywords = "cross-sectional incidence estimation, incidence, Uganda, validation",
author = "Laeyendecker, {Oliver B.} and Gray, {Ronald H} and Mary Grabowski and Reynolds, {Steven James} and Anthony Ndyanabo and Joseph Ssekasanvu and Fernandez, {Reinaldo E.} and Wawer, {Maria J} and David Serwadda and Quinn, {Thomas C}",
year = "2019",
month = "4",
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doi = "10.1089/aid.2018.0207",
language = "English (US)",
volume = "35",
pages = "364--367",
journal = "AIDS Research and Human Retroviruses",
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TY - JOUR

T1 - Validation of the Limiting Antigen Avidity Assay to Estimate Level and Trends in HIV Incidence in an A/D Epidemic in Rakai, Uganda

AU - Laeyendecker, Oliver B.

AU - Gray, Ronald H

AU - Grabowski, Mary

AU - Reynolds, Steven James

AU - Ndyanabo, Anthony

AU - Ssekasanvu, Joseph

AU - Fernandez, Reinaldo E.

AU - Wawer, Maria J

AU - Serwadda, David

AU - Quinn, Thomas C

PY - 2019/4/1

Y1 - 2019/4/1

N2 - The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 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. Sera from persons seen in two surveys (2008-2009 and 2012-2013) 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 with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95% confidence interval (CI) 0.90-1.23] in 2008-2009 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 2008-2009 and 2.55/100 py (95% CI 1.51-3.59) in 2012-2013 (a significant increase, p < .05.) However, using a subtype-specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95% CI 0.44-1.33) in 2008-2009 and 0.67% (95% CI 0.00-1.68) in 2012-2013, approximating to the observed incidence trends. 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.

AB - The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 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. Sera from persons seen in two surveys (2008-2009 and 2012-2013) 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 with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95% confidence interval (CI) 0.90-1.23] in 2008-2009 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 2008-2009 and 2.55/100 py (95% CI 1.51-3.59) in 2012-2013 (a significant increase, p < .05.) However, using a subtype-specific MDRI and FRR, the subtype adjusted incidence was 0.88% (95% CI 0.44-1.33) in 2008-2009 and 0.67% (95% CI 0.00-1.68) in 2012-2013, approximating to the observed incidence trends. 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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