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Development and Evaluation of a Modified Fourth-Generation Human Immunodeficiency Virus Enzyme Immunoassay for Cross-Sectional Incidence Estimation in Clade B Populations.


ABSTRACT:

Background

Accurate methods for cross-sectional incidence estimation are needed for HIV surveillance and prevention research. We developed an avidity assay based on the fourth-generation Genetic Systems HIV Combo Ag/Ab EIA (Bio-Rad Combo assay) and evaluated its performance.

Materials and methods

The Bio-Rad Combo assay was modified incubating samples with and without 0.025?M diethylamine (DEA). The avidity index (AI) was calculated as the ratio of the DEA-treated to untreated result for a specific sample. We analyzed 2,140 samples from 808 individuals from the United States with known duration of HIV infection. The mean duration of recent infection (MDRI) and the false-recent rate (FRR, fraction of samples from individuals known to be infected >2 years misclassified as recent) were calculated for AI cutoffs of 20%-90% for the avidity assay alone and in combination with a viral load assay (VL, limit of detection 400 copies/ml). Factors associated with misclassification of samples collected ?2 years after infections were also evaluated.

Results

The MDRI for the Bio-Rad Combo Avidity assay ranged from 50 days using an AI cutoff of 20% to 276 days using an AI cutoff of 90%; the FRR ranged from 0% to 9%. When samples with a VL <400 copies/ml were classified as nonrecent, the FRRs were reduced approximately twofold and the MDRI estimates were reduced by ?20%. An AI cutoff of 50% provided an MDRI of 135 days with an FRR of 2.1%. All samples from elite suppressors had an AI >80%. In adjusted analysis, viral suppression and low CD4 cell count were significantly associated with misclassification among individuals infected >2 years.

Conclusions

This modified Bio-Rad Combo Avidity assay may be a useful tool for cross-sectional HIV incidence estimation. Further research is needed to evaluate use of this assay in combination with other assays to accurately estimate population-level HIV incidence.

SUBMITTER: Kirkpatrick AR 

PROVIDER: S-EPMC4971410 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

Development and Evaluation of a Modified Fourth-Generation Human Immunodeficiency Virus Enzyme Immunoassay for Cross-Sectional Incidence Estimation in Clade B Populations.

Kirkpatrick Allison R AR   Patel Eshan U EU   Celum Connie L CL   Moore Richard D RD   Blankson Joel N JN   Mehta Shruti H SH   Kirk Gregory D GD   Margolick Joseph B JB   Quinn Thomas C TC   Eshleman Susan H SH   Laeyendecker Oliver O  

AIDS research and human retroviruses 20160505 8


<h4>Background</h4>Accurate methods for cross-sectional incidence estimation are needed for HIV surveillance and prevention research. We developed an avidity assay based on the fourth-generation Genetic Systems HIV Combo Ag/Ab EIA (Bio-Rad Combo assay) and evaluated its performance.<h4>Materials and methods</h4>The Bio-Rad Combo assay was modified incubating samples with and without 0.025 M diethylamine (DEA). The avidity index (AI) was calculated as the ratio of the DEA-treated to untreated res  ...[more]

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