Understanding the BED capture enzyme immunoassay (CEIA): measuring HIV-1 incidence in cross-sectional studies
Date
2013-05-08
Authors
Marinda, Edmore
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Abstract
Measuring HIV incidence has proved challenging over the years. A number of
serological HIV assays have been proposed, and among these, the BED Capture
Enzyme Immunoassay (CEIA) is one of the more widely used. Although the assay
performs well among known seroconverting panels, it has been shown to classify
some long term infected patients as being recently infected. Information on the
performance of the BED assay among low CD4 cell count patients and those on antiretroviral
therapy is limited. The risk of onwards transmission of HIV has been
reported to be elevated around the seroconversion period compared to the chronic
stage of infection. RNA viral load has been reported as the strongest predictor of HIV
transmission compared to other HIV markers. Understanding how these markers
influence the relationship between the likelihood of being recently infected and the
BED assay might help in understanding some of the shortcomings of the BED assay.
The main aim of this study was to understand the properties of the BED assay. The
performance of the BED assay among advanced HIV disease patients and the
influence of ART on BED levels once patients started treatment was investigated. The
BED assay and CD4 cell count were used to quantify the risk of in utero and intrapartum
transmission to their infants among women believed to have seroconverted
during pregnancy. The influence of viral load, haemoglobin and mid-upper arm
circumference was investigated on the relationship between the probability of being
recently infected and BED ODn levels.
Methods
Cryopreserved plasma samples from HIV patients on the national antiretroviral
treatment (ART) rollout programme at Tygerberg Hospital HIV clinic, South Africa,
iv
were used to investigate the effect of ART on BED ODn levels once patients
commenced treatment. Mixed effect logistic regression models accounting for
multiple readings per patient were used.
To investigate the risk associated with seroconversion during pregnancy HIV
seropositive women who had just given birth were classified into mutually exclusive
groups according to their likelihood of having recently seroconverted using BED and
CD4 cell count levels. Multinomial logistic regression models adjusting for other
factors were used to assess the risk of MTCT in utero and intra-partum infection
comparing these groups.
To investigate the relationship between BED ODn levels and the probability of being
recently infected, BED data from known HIV infected women and women who
seroconverted over a 2 year period was used. Fractional polynomial regression
models that allow for non-linear functions to be fitted were used, and the influence of
viral load, haemoglobin and mid-upper arm circumference was assessed through
multi-variable models. Data from the Zimbabwe Vitamin A for Mothers and Babies
(ZVITAMBO) project, a double blinded treatment-placebo trial was used for these
last two objectives.
Results
Patients with very low CD4 cell counts were more likely to test false recently infected
according to the BED assay than other patients. ART changed BED ODn kinetics
among HIV patients on treatment. Over half of advanced disease stage patients were
likely to be classified as being recently infected according to the BED assay 2 years
into ART treatment.
v
Women who seemed to have seroconverted during pregnancy had elevated risk of
transmitting HIV in-utero compared to chronic HIV patients. BED and CD4 cell
count were not predictive of risk of intra-partum infections attributed to
seroconversion during pregnancy.
The relationship between the probability of being recently infected with HIV and
BED ODn levels was described better using Fractional Polynomial regression models
than using a linear model in BED ODn or a model in which the BED ODn was
categorised. Viral load and haemoglobin were important independent predictors of
incident infections.
Conclusions
If the BED assay is to be used for HIV incidence estimations patients on ART should
be accounted for. The BED assay together with other HIV serological markers can be
used as prognostic tools to assess the risk of HIV transmission.
The risk of in-utero transmission of HIV is higher among women who seroconvert
during pregnancy. Repeat HIV testing among pregnant women may help in
identifying women who seroconvert during pregnancy, and these women will benefit
from Prevention of Mother-to-Child transmission (PMTCT) programmes.
It was found that additional markers such as viral load and haemoglobin did not alter
the relationship between the probability of having been recently infected and BED
ODn.
Description
Thesis (Ph.D.(Public Health))--University of the Witwatersrand, Faculty of Health Sciences, 2012.
Keywords
IgG, BED, HIV incidence, seroconversion, fractional polynomials