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

Abstract

The aim of this study was to estimate the rate of misclassification in treated HIV patients who initiated treatment at the chronic stage of HIV infection using an enzyme immunoassay (EIA) that discriminates between recent infection (RI; within 6 months) and established infection. The performance of EIA-RI was evaluated in 96 HIV-1 chronically infected patients on highly active antiretroviral therapy (HAART) with an undetectable viral load (VL) for at least 3 years. Demographic data, HIV-1 viral load, CD4؉ T-cell count, viral subtype, and treatment duration were collected. The subset of misclassified patients was further analyzed using samples collected annually. The impact on incidence estimates was evaluated by simulation. The specificity in treated patients was significantly lower (70.8 to 77.1%) than that observed in untreated patients (93.3 to 99.3%, P < 0.001). Patients falsely classified as recently infected had been treated for a longer period and had longer-term viral suppression than those correctly classified. The loss of specificity of the test due to treatment may have a dramatic impact on the accuracy of the incidence estimates, with a major impact when HIV prevalence is high. The cross-sectional studies intended to derive HIV incidence must collect information on treatment or, alternatively, should include detection of antiretroviral drugs in blood specimens to rule out treated patients from the calculations. Monitoring the incidence of human immunodeficiency virus type 1 (HIV-1) infections is critical both for surveillance of the epidemic and evaluation of prevention programs. The concept of immunoassays for recent infections, named serological testing algorithm for recent HIV seroconversion (STARHS), was introduced more than 10 years ago by Janssen et al. (9) and, since then, has been considered a major tool allowing the estimation of HIV incidence in cross-sectional studies (for recent reviews, see references 4, 6, and 16). Although several technical approaches have been used, the shared rationale for recent infection testing algorithms (RITA) is to discriminate recent from long-standing infections based on maturation of HIV-specific antibody responses, predominantly using the measurement of antibody levels or antibody avidity toward major antigenic proteins or epitopes of 9,18,20,24,28,31). 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...

Screening for Human Immunodeficiency Virus Infection by Use of a Fourth-Generation Antigen/Antibody Assay and Dried Blood Spots: In-Depth Analysis of Sensitivity and Performance Assessment in a Cross-Sectional Study

“…The first one corresponds to acute or recent infections when the antibody response is just emerging (11,12). The second one, much less recognized, is that of patients treated efficiently, particularly, early after infection, for whom the lack of antigenic stimulation leads to a regular decrease, even a vanishing, of anti-HIV antibodies (21)(22)(23)(24). In the present study, we wanted to better characterize the sensitivity of the Genscreen Ultra HIV Ag-Ab combo assay, taking into account these limitations, particularly, by capitalizing on a large cross-sectional survey in which the biological results obtained from DBS with this assay were compared to the self-reported HIV status.…”

“…The first is the situation of acute or recent infection, when only a low antibody titer or a low antibody avidity is present (15). The second is the situation of individuals who have been treated efficiently, particularly early after infection, and remain with an undetectable virus load for many years (21)(22)(23)(24). In this case, the lack of antigenic stimulation leads to a regular decrease of antibody level that might alter the performance of detection when using DBS.…”

Short Communication: Defining Optimality of a Test for Recent Infection for HIV Incidence Surveillance

“…Currently available, and perhaps all conceivable, tests for recent infection present a subtle problem in that some individuals who have been infected for long periods of time may nevertheless yield spurious ''recent'' results. [15][16][17] With some simplifying assumptions (which are often not numerically catastrophic) it has been shown how this ''false-recent'' phenomenon can be intuitively understood as requiring a ''subtraction'' of the estimated number of ''falserecent'' results from the observed number of ''recent'' results. [18][19][20][21] More recently, a very general analysis has been obtained by introducing a convenience recency time cut-off, T (presumed to be 1 year for the purposes of model scenarios throughout this article), which represents the time, postinfection, after which a ''recent'' test result is a ''false-recent'' result.…”

Development of an avidity assay for detection of recent HIV infections

“…Based on combined assessment of retrospective and prospective HIV samples, the FRR of the assay is 0.89% (95% CI: 0.24-2.3%). Low CD4 count, antiretroviral therapy, AIDS-defining illness, elite controllers, undetectable viral load and HIV subtypes can influence the FRR of incidence assays (Chawla et al, 2007;Selleri et al, 2007;Re et al, 2010;Poropatich and Sullivan, 2011;Chaillon et al, 2012;Laeyendecker et al, 2012;Hauser et al, 2014). Only three longstanding HIV infected patients from the retrospective study had a low AI.…”