Short Communication: Effects of Low HIV Type 1 Load and Antiretroviral Treatment on IgG-Capture BED-Enzyme Immunoassay

Abstract

The IgG-capture BED-enzyme immunoassay (BED-CEIA) is used widely at present to detect recent HIV-1 seroconversion. However, antibody levels and antibody kinetics are impacted by HIV-1 load and antiretroviral treatment, which may have a significant effect on the assay results. In this study, we analyzed serial samples from 11 patients with recent infection, including four patients treated by structured treatment interruption (STI), and compared the results with those of 10 untreated and 7 treated patients with chronic infection. The BED-CEIA missidentified one long-term nonprogressor hemophiliac with an extremely low HIV-1 load and five patients with chronic infection who received antiretroviral treatment. We also found that the ODn values increased slowly in patients with recent infection and low HIV-1 loads and that the ODn values fluctuated in parallel with HIV-1 load during STI. Our data indicate that the results of BED-CEIA are influenced by HIV-1 load and antiretroviral treatment. Care should be taken when interpreting the results of BED-CEIA, especially in individuals with low HIV-1 loads. Those on antiretroviral treatment should be excluded from BED-CEIA testing to improve the predictive value of detecting recent infections.

Specificity of Four Laboratory Approaches for Cross-Sectional HIV Incidence Determination: Analysis of Samples from Adults with Known Nonrecent HIV Infection from Five African Countries

“…7 Factors previously associated with misclassification of the BED-CEIA in African populations include low HIV viral load, low CD4 cell count, and long-term antiretroviral therapy (ART). [8][9][10][11][12] However, none of those studies has compared false-recent misclassification among demographically similar populations in different African countries, and little is known about the frequency and nature of false-recent misclassification using the avidity assay, especially in an African setting.…”

Decreased Specificity of an Assay for Recent Infection in HIV-1-Infected Patients on Highly Active Antiretroviral Treatment: Implications for Incidence Estimates

“…Several limitations of the RITA have been reported regularly, and there have been debates about their real validity and, hence, their value for incidence measurements (6). Among these limitations, the interfering effect of highly active antiretroviral treatment (HAART) has been clearly documented when HAART was initiated in patients with primary HIV-1 infection and, also, in patients with chronic infection (2,8,17,25). By stopping the viral replication, the early virostatic treatment may prevent the development of the HIV-1-specific antibody response, either quantitatively (antibody level) or qualitatively (avidity), leading to an unacceptably high rate of falserecent results in samples collected more than 1 year after infection (2,8,25).…”

“…Among these limitations, the interfering effect of highly active antiretroviral treatment (HAART) has been clearly documented when HAART was initiated in patients with primary HIV-1 infection and, also, in patients with chronic infection (2,8,17,25). By stopping the viral replication, the early virostatic treatment may prevent the development of the HIV-1-specific antibody response, either quantitatively (antibody level) or qualitatively (avidity), leading to an unacceptably high rate of falserecent results in samples collected more than 1 year after infection (2,8,25). In accordance with this, although not analyzed in the context of RITA, it was previously reported that even entire seroreversion could be reached when HAART is initiated during acute/early HIV infection, suggesting that ongoing antigenic stimulation may be required to maintain HIV-1-specific humoral responses (7,10,12).…”

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

“…Low viral load (VL) (natural 10 or drug-induced 11 ), low CD4 cell count, 12,13 and HIV subtype D 14 are associated with misclassification by cross-sectional incidence assays. The performance of incidence assays can be characterized by two variables: the mean duration of recent infection (MDRI, the average amount of time individuals are considered recently infected for a given assay or algorithm), and the false recent rate (FRR, the frequency that individuals with long-term infection are misclassified as recently infected).…”