Immune Responses in Ugandan Women Infected With Subtypes A and D HIV Using the BED Capture Immunoassay and an Antibody Avidity Assay

Abstract

Introduction: Analysis of samples from Uganda using serologic HIV incidence assays reveal that individuals with subtype D infection often have weak humoral immune responses to HIV infection. It is unclear whether this reflects a poor initial response to infection or a waning antibody response later in infection. Materials and Methods: Samples (N=2614) were obtained from 114 women aged 18-45 in the Ugandan GS Study cohort (2001-2009; 82 subtype A, 32 subtype D; median 23 samples/women, range 3-41 samples, median follow-up of 6.6 years). Samples were analyzed using the BED capture immunoassay (cutoff 0.8 OD-n) and the avidity assay (cutoff 90% AI). Antibody maturation was assessed by having the BED-CEIA or avidity value exceed the assay cutoff 1 or 2 years after infection. A waning antibody response was measured by having the BED-CEIA or avidity value fall >20% below the maximum value. Results: For the BED-CEIA, eight women with subtype A infection and three women with subtype D infection never progressed past the cutoff value (median 5.9 years follow-up after infection). Six women with subtype D infection never achieved an AI >90%. Subtype did not impact the proportion of women whose assay values regressed by >20% of the maximal value (for BED-CEIA: 33% for A, 41% for D, p=0.51; for avidity: 1% for A, 6% for D, p=0.19). Discussion: The higher frequency of misclassification of individuals with long-term subtype D infection as recently infected using serologic incidence assays reflects a weak initial antibody response to HIV infection that is sustained over time.

Impact of HIV Subtype on Performance of the Limiting Antigen-Avidity Enzyme Immunoassay, the Bio-Rad Avidity Assay, and the BED Capture Immunoassay in Rakai, Uganda

“…Multiassay algorithms have been developed that include serological assays with relaxed cutoff values; these algorithms maximize the identification of recently infected individuals, while providing a high level of specificity. 12 Further studies are needed to determine whether the lower LAg-Avidity EIA values seen in subtype D reflect a muted early antibody response to HIV infection (similar to what was observed in previous studies of the BED-CEIA and Bio-Rad Avidity assay 29 ) or a waning of an initially robust antibody response. Additional studies are needed to determine the impact of viral suppression (natural or HAART induced) on the performance of the LAg-Avidity EIA.…”

Comparison of Antibody Responses to HIV Infection in Ugandan Women Infected with HIV Subtypes A and D

“…This type of misclassification has been observed at higher rates in infected with subtype D HIV compared to other subtypes. [7][8][9][10][11] Previous reports have also demonstrated an association between subtype D HIV infection and disease progression. 12,13 In Eastern Africa, subtype D infection is associated with a faster decline in CD4 cell count and shorter survival, compared to subtype A infection.…”

“…Previous studies have evaluated the avidity of the anti-HIV antibody response in individuals with subtype A vs. D infection using a modified version of the Genetic Systems 1/2 + O ELISA (Bio-Rad-Avidity assay). [7][8][9]11 In those studies, lower antibody avidity was observed in both early and established subtype D infection. 7 The United States Centers for Disease Control recently developed a limiting antigen avidity assay (LAg-Avidity assay) for cross-sectional HIV incidence estimation.…”

“…[7][8][9]11 In those studies, lower antibody avidity was observed in both early and established subtype D infection. 7 The United States Centers for Disease Control recently developed a limiting antigen avidity assay (LAg-Avidity assay) for cross-sectional HIV incidence estimation. 15,16 This assay was developed to reduce the rate at which individuals with long-standing infection are misclassified as having recent infection.…”

Computational analysis of antibody dynamics identifies recent HIV-1 infection

“…[6][7][8][9][10]. This is often due to a high false recent rate (FRR) (i.e., specimens infected for more than a recency time cutoff time "T," often chosen to be 2 years, that are classified as recently infected) (6) and a mean duration of recent infection (MDRI) of approximately 4-5 months (6,11).…”