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

Longosz, Andrew F. BS*; Morrison, Charles S. PhD, MPH; Chen, Pai-Lien PhD; Arts, Eric PhD; Nankya, Immaculate MD, PhD; Salata, Robert A. MD; Franco, Veronica BS§; Quinn, Thomas C. MD, MSc*,§; Eshleman, Susan H. MD, PhD§; Laeyendecker, Oliver MS, MBA, PhD*,§

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 April 2014 - Volume 65 - Issue 4 - p 390–396
doi: 10.1097/QAI.0000000000000006
Basic and Translational Science

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 years in the Ugandan Genital Shedding and Disease Progression 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% Avidity Index). Antibody maturation was assessed by having the BED capture enzyme immunoassay (BED-CEIA) or avidity value exceed the assay cutoff 1 or 2 years after infection. The waning antibody response was measured by having the BED-CEIA or avidity value fall >20% below the maximum value.

Results: For the BED-CEIA, 8 women with subtype A infection and 3 women with subtype D infection never progressed previously the cutoff value (median, 5.9 years follow-up after infection). Six women with subtype D infection never achieved an avidity index >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.

*Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore, MD;

Clinical Sciences, Family Health International 360, Durham, NC;

Case Western Reserve University, Cleveland, OH; and

§Johns Hopkins University School of Medicine, Baltimore, MD.

Correspondence to: Oliver Laeyendecker, MS, MBA, PhD, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, 855 North Wolfe Street, Room 538A, Baltimore, MD (e-mail: olaeyen1@jhmi.edu).

Supported by the Centers for Disease Control and Prevention (CDC) under contract no. 200-2010-35109-00001. The research was also supported by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research, of the National Institutes of Health (NIH), Department of Health and Human Services (DHHS) (UM1-AI068613) and (NIAID) R01-AI095068. An additional funding was provided in part by the Division of Intramural Research, NIAID, and NIH.

Presented as a poster (#1057) at Conference on Retroviruses and Opportunistic Infections (CROI) 2013, March 3–6, 2013, Atlanta, GA.

The authors have no funding or conflicts of interest to disclose.

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Received September 10, 2013

Accepted September 10, 2013

© 2014 by Lippincott Williams & Wilkins